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7 We warmly welcome you to the 6th International Bioengineering Congress (BEC2013) and 19th International Biomedical Science and Technology Symposium (BIOMED2013) in Izmir, Turkey between November, The Congress aims to gather researchers from the entire spectrum of the multi-disciplinary fields of bioengineering with a special emphasis on human welfare. The BIOMED Symposium series is held every year by a different research group in Turkey aiming to bring scientists in both basic and applied research in biomedical science and technology. These two meetings will be held jointly to gather researchers from multidisciplinary fields to encourage the exchange of new information, support interchange of opinions and establish effective communication between them. The official language of the Congress and Symposium is English. We would like to invite you and your colleagues to participate to these events. We look forward to the scientific exchange, and the profile you will bring to our meetings. Prof. Dr. Fazilet VARDAR SUKAN Chair of the BEC2013 Prof. Dr. S. İsmet DELİLOĞLU GÜRHAN Chair of the BIOMED2013 i

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9 Local Organising Committee S. İsmet Deliloğlu Gürhan, Chair Aylin Şendemir Ürkmez, Vice-Chair Hülya Yılmaz Temel, Secretariat Begüm Zeybek Ege University Cansu Görgün Ege University Cenk Çelik Ege University Çiğdem Serdengeçti Ege University Ece Bayır Ege University Fazilet Vardar Sukan Ege University İlknur Alpak Ege University Kemal S. Korkmaz Ege University Müge Anıl Ege University M. Can Minaz Ege University O. Mert Duman Ege University Özlem Yeşil Çeliktaş Ege University Şükrü Öztürk Ege University International Organising Committee Buket Erer Del Castello Ege University Erhan Pişkin Hacettepe University Eser Elçin Gazi University Fazilet Vardar Sukan Ege University Gamze Torun Köse Yeditepe University Kemal S. Korkmaz Ege University Kezban Ulubayram Hacettepe University Khosrow Mottaghy- Aachen University Menemşe Gümüşderelioğlu Hacettepe University Murat Elçin Ankara University Nesrin Hasırcı Middle East Technical University Ozan Karaman University of South Carolina Özlem Yeşil Çeliktaş Ege University Russell D. Jamison Virginia Commonwealth University Sultan Gülçe İz University of California Irvine Tanseli Nesil University of Virginia Vasıf Hasırcı Middle East Technical University Yannis Missirlis Patras University iii


11 PROGRAM Nov. 12, 2013, Tuesday 10:00-12:00 Registration 12:00-13:00 Lunch 13:00-13:30 Opening Ceremony Candeğer Yılmaz, Süheyda Atalay, Fazilet Vardar Sukan, S. İsmet Deliloğlu Gürhan :30 Plenary Session Glyn Stacey Critical Issues for Suitability of Stem Cell Lines for Clinical Use 14:30-15:00 Coffee Break 15:00-16:45 Session 1 Biomaterials Chair Persons: Vasıf Hasırcı, Khosrow Mottaghy Session 2 Biosensors Chair Persons: Arzum Erdem Gürsan, Sinan Akgöl 15:00-15:30 O-BM01 Vasıf Hasırcı Better implants with proper design of processing and surfaces O-BS01 Mustafa Kemal Sezgintürk Biosensors: Past, Present and Future 15:30-16:00 O-BM02 Aylin Şendemir Ürkmez Controlling Neural Cell Behavior at Biomaterial Interfaces O-BS02 Arzum Erdem Gürsan Nanomaterials integrated Electrochemical Biosensor Technologies 16:00-16:15 O-BM03 Murat Şimşek Electrospun PEO Nanofiber-Coated Titanium Surfaces O-BS03 Filiz Kuralay 16:15-16:30 O-BM04 Şükran ŞEKER Nanotoxicity of SnO2 and ZnO Nanoparticles in Human Periodontal O-BS04 Ligament Fibroblast and Mouse Dermal Fibroblast Cells Münteha Nur Sonuç Carbohydrate-Sensitive Microtransporters for Isolating Sugars and Cells An Immunosensor for Ultrasensitive Detection of Parathyroid Hormone 16:30-16:45 O-BM05 O-BS05 Sabiha Demirci Homocysteine Biosensor by Gold Piezocrystals 16:45 18:30 Poster Session (Posters in all topics will be on display throughout the Symposium) 18:30 Welcome Coctail v

12 Nov. 13, 2013, Wednesday 09:00-10:00 Plenary Session Yannis Missirlis "All the Appropriate Signals are Necessary for Engineering Proper Tissues" 10:00-10:30 10:30-12:00 Coffee Break Session 3 Session 4 Biomedical Instrumentation Regenerative Medicine Chair Persons: Mehmet Engin, Ersin Koylu Chair Persons: Glyn Stacey, Seda Vatansever 10:30-11:00 O-BMI01 Merve Uluğ Evren Biomedical Visualisation O-RM01 Murat Elçin 11:00-11:15 O-BMI02 Barış Oğuz Gürses The Concept Design of Microrobot Based Surgery Robot for the Treatment of Non - Communicating Hydrocephallus 11:15-11:30 O-BMI03 Cenk Çelik More than a picture: Biomedical Illustration 11:30-11:45 O-BMI04 Yusuf Efteli ECG Signals Based Diagnosis Using Artificial Neural Networks O-RM03 Tuğba Dursun 11:45-12:00 O-BMI05 İbrahim Akkaya O-RM02 Seda Vatansever Breast Cancer Monitoring The Investigation of Diffuse Optical Tomography Simulations for O-RM04 Öznur Başkan Biomimetic Tissue Engineering in a Bioreactor with Adipose Mesenchymal Stem Cells Clinical Potential Use of Differentiated Cells from Embryonic or Mesenchymal Stem Cells Effects of the Architecture of a Nerve Guide for Use in the Treatment of Spinal Cord Injury Effects of Low Intensity Vibratory Signals on Ultrastructure of Mesenchymal Stem Cells During Adipogenic Committment 12:00-14:00 Lunch 14:00-16:00 Session 5 Translational Medicine Chair Persons: Richard Oreffo, Semih Aydoğdu Session 6 Artificial Organs Chair Persons: Kamuran Kadıpaşaoğlu, Murat Elçin 14:00-14:30 O-TM01 Richard Oreffo Bridging the Gap-Skeletal Stem Cell Based Strategies for Bone Regeneration O-AO01 Kamuran Kadıpaşaoğlu Development of the First Turkish Axial-flow LVAD and its Hemodynamic Testing Platform 14:30-15:00 O-TM02 Semih Aydoğdu Biomaterials in Orthopaedics: More Problems than Benefits? O-AO02 Khosrow Mottaghy Artificial Organs and Blood Interaction: Haemorheological Aspects 15:00-15:15 O-TM03 Utku Kürşat Ercan 15:15-15:30 O-TM04 Ali Poorkhalil 15:30-15:45 O-TM05 Saad Sabbar Dahham 15:45-16:00 O-TM06 Mahmut Ozan Gökkan Antimicrobial Effect Chemical Changes In Plasma-Treated NAC Solution Leading to O-AO03 Emir G. Eken Approach New RBC Trauma Model Applying a Semi-Empirical Hemolysis O-AO04 Ali Kashefi Asper) Anti-Proliferative and Anti-Fungal Activities of Toad Skin Secretion (Bufo O-AO05 Kevser Banu Köse Tissue Pshyological Conditions In Semi-Infinite Scattering Medium The Heat Calculation Based Monte Carlo Modelling For Monitoring of O-AO06 Ali Rasouli Design, Construction and Feedback Control of an Elastance-Driven Mock Circuit A New Oxygenation and Integrated Pump System for Extra-Corporeal Application Blood Flow Analysis Through Right Ventricle-Pulmonary Artery Conduit Stenosis by Computational Fluid Dynamics Modeling and Simulation of Blood Oxygenation in a Hollow-Fiber Membrane Oxygenator (HFMO) 16:00-16:30 Coffee Break 16:30-17:45 Session 5 (Continued) Translational Medicine Chair Persons: Gülperi Öktem, Khosrow Mottaghy Session 7 Regenerative Medicine Chair Persons: Yuanyuan Zhang, Aylin Şendemir-Ürkmez 16:30-17:00 O-TM07 Gülperi Öktem Cancer and Stem Cell O-RM06 Yuanyuan Zhang Human Urine-Derived Stem Cells: Characterization and Potential Cell-Based Therapy 17:00-17:15 O-TM08 Melis Olçum 17:15-17:30 O-TM09 Ali Khachab Daily Mechanical Vibrations Reduce Number of Aggressive Type Breast Cancer Cells by Interfering with Their Cell Cycle O-RM07 Ozan Karaman Fabrication of Osteon-Mimetic Microtubes for Bone Regeneration Altitude Training A New Respiratory Training System w ith a Controlled CO 2 Elimination for High O-RM08 Açelya Yılmazer Aktuna 17:30-17:45 O-TM10 Mehrnaz Moaddab A Novel Approach to Measure CO 2 Transfer Rate Through an Artificial Lung O-RM09 Aylin Şendemir-Ürkmez in vivo Somatic Cell Reprogramming towards Pluripotency within the Mouse Tissue Chitosan/Poly-L-Lysine Composite Tubes in Sciatic Nerve Damages 17:45-19:00 19:00 Poster Session Dinner vi

13 Nov. 14, 2013, Thursday 09:00-10:30 Session 8 Biomaterials Chair Person: Yannis Missirlis, Kezban Ulubayram 09:00-09:30 O-BM06 Kezban Ulubayram New approaches in Designing Antibacterial Polymeric Surfaces 09:30-09:45 O-BM07 Cemile Kılıç Characterization of Micropatterned Collagen Films for Corneal Stroma Engineering 09:45-10:00 O-BM08 Torsten Müller Quantitative Characterization of Biomaterials and Their Interaction with Living Cells by AFM 10:00-10:15 O-BM09 Esen Sayın Micropatterned Collagen-Fibroin Films for Guidance of Adipose Derived Stem Cells 10:15-10:30 O-BM10 Filiz Kara Surface Modification of Biomedical Polyurethanes with Chitosan for Antibacterial and Anti-Adhesive Purpose 10:30 11:00 Coffee Break 11:00-12:45 Session 9 Commercialization of Bio-based Research Chair Persons: Russell D. Jamison, Fazilet Vardar Sukan 11:00-11:30 O-CB01 Russell D. Jamison Universities as Engines of Wealth Creation: Rethinking the Commercialization Model 11:30-11:45 O-CB02 Cansel Öğütçü R&D Strategies in Biomaterial Production 11:45-12:15 O-CB03 Fazilet Vardar Sukan Horizon 2020 Strategies in Bio-based Research and Innovation 12:15-12:30 Discussion on Horizon 2020 Collaboration Possibilities 12:30-14:00 Lunch 14:00-16:30 Panel Precompetitive Research in Biomedical Technologies Moderator: Fazilet Vardar Sukan Panelists: Cemil Arıkan Russell D. Jamison Stephen Mayfield Murat Özgören 16:30-17:00 Coffee Break 17:00-18:00 Award Ceremony and Closing Remarks 19:00 Dinner vii

14 Accepted Posters Biomaterials P-BM01 H. Seda VATANSEVER Biomaterial Selection For Mouse Spinal Cord Injury Models Using Mouse Embryonic Stem Cell-Derived Neuron-Like Cells P-BM02 S. Seda GÜNEŞ Chitosan Nanocomposite Microspheres as a Controlled Drug Delivery System P-BM03 Azade YELTEN Mechanical Properties of the Sol-Gel Derived Alumina-Bovine Hydroxyapatite Composites P-BM04 Cenk ÇELİK The Effects of Spirulina/PCL Biocomposite Scaffolds on Bone Marrow Derived Mesenchmal Stem Cells and Keratinocytes P-BM05 Çiğdem DEMİRKAYA Optimization of Gelatin Films Crosslinked by EDC/NHS and Genipin Methods as Cell Attachment Substrates P-BM06 Ozan KARAMAN Osteogenic Differentiation of Marrow Stromal Cells in Hydrolytically Degradable PEG Based Hydrogels P-BM07 Hazal AYDOĞDU Porous Pullulan Microcarriers for Osteochondral Tissue Regeneration P-BM08 Hale Melis SOYLU Synthesis, Radiolabeling and Bioevaluation of an Imidazolium TFSI Salt P-BM09 Murat ŞİMŞEK Polyethylene Oxide Nanofibers: Effects of Electrospinning and Crosslinking Conditions P-BM10 Tohid HAJİBABAEİ Collagen Chemical Bonding of the Silicone Hollow Fiber Surface to Enhance Endothelial Cell Attachment P-BM11 Utku TİRİÇ Effect of Mg Addition on Electrochemically Deposited CaP Coatings on Ti6Al4V Substrates P-BM12 Tülay KOÇ Corrosion Properties of Electrodeposited CaP Coatings With Different PVA Addition P-BM13 Bensu BAKIN Investigation of Corrosion Properties of Electrochemically Deposited Mg Substituted CaP Coatings on Ti6Al4V Substrates P-BM14 Aylin M. In vitro Degradation and Bioactivity of V +3 Doped Borate Bioactive Glass Scaffolds DELİORMANLI P-BM15 Aylin M. Preparation and Characterization af Electro-Spun 45S5 Bioactive Glass Nanofibers DELİORMANLI P-BM16 Zalike KESKİN Bacterial Cellulose Membranes Produced in Static Culture as a Tissue Scaffold for Skin Fibroblast Cells and Mechanical Characterization P-BM17 Filiz KARA Synthesis and Characterization of Polyurethanes for Biomedical Applications Regenerative Medicine P-RM01 Begüm ZEYBEK Three Dimensional Cross-Linked Collagen Skin Equivalent Model P-RM02 Faezeh FAGHİHİ A Comparison of the Osteoinductive Potential of Purmorphamine on Human Mesenchymal Stem Cells in 2D and 3D Culture Systems P-RM03 Hatice ERCAN Evaluation of Decellularized Bovine Cardiac Tissue for Cell Culture and as a Guiding Template P-RM04 Şükrü ÖZTÜRK Comparison of in vitro Three-Dimensional (3D) Microtissue Forming Potential of Different Cell Types for Regenerative Medicine Applications P-RM05 Şeyma BEKTAŞ Design of Various Hydrogels for 3D Bioprinting Method and Investigation of Cell Viability Biosensors P-BS01 Munteha Nur SONUÇ Design of an Ultrasensitive Impedimetric Biosensor Using Anti-PTH for Quantification of Parathyroid Hormone P-BS02 Çağrı ALTUĞ Electrochemical Impedance Spectroscopy Based Biosensor for the Detection of Cytochrome C P-BS03 Filiz KURALAY Storage Stability of Electrochemical DNA Biosensors P-BS04 Ece EKŞİN Electrochemical Determination of Homocysteine at Disposable Graphite Electrodes P-BS05 Gülşah ÇONGUR Electrochemical Investigation of Topotecan-DNA Interaction by Using Carbon Nanotubes Modified Pencil Graphite Electrodes Translational Medicine P-TM01 Muge ANIL Developing a Three-Dimensional (3D) Cancer Tissue Model With Tissue Engineering Approach P-TM02 Seval BÜLBÜL Hope of Proton and Hadron Therapy in Cancer Treatment P-TM03 Osman Mert DUMAN Effects of in vitro Mechanical Tension on Central Nervous System Neurons P-TM04 Amirhossein SAHEBKAR Investigation of the Effects of Bioavailability-Enhanced Curcumin on Serum Trace Element and Superoxide Dismutase Status P-TM05 Yunes PANAHI Effects of a Bioavailability-Improved Curcuminoids on Pulmonary Function and Oxidative Stress in Patients with Mustard-Induced Chronic Pulmonary Disease P-TM06 Serap ERDEM Isolatıon and Identification of Cancer Stem-Like Cells from Human Leukemia Cells KURUCA Biomedical Instrumentation P-BMI01 Livio David REINOSO P300 Paradigm Based on Brain-Computer Interface Implementation in 32 Bits Microcontroller: Preliminary Analysis viii

15 INVITED SPEAKERS Arzum ERDEM GURSAN Department of Analytical Chemistry, Ege University Glyn STACEY UK Stem Cell Bank Gülperi ÖKTEM Department of Histology and Embryology, Ege University Kamuran KADIPAŞAOĞLU Department of Biomedical Engineering, Bahçeşehir University Kezban ULUBAYRAM Department of Nanotechnology and Nanomedicine, Hacettepe University Khosrow MOTTAGHY Department of Physiology, Aachen University Merve EVREN Department of Biotechnology, Ege University Murat ELÇİN Department of Biochemistry, Ankara University ix

16 Mustafa Kemal SEZGİNTÜRK Department of Food Engineering, Namık Kemal University Richard OREFFO Faculty of Medicine, University of Southampton Russell D. JAMISON Department of Biomedical Engineering, Virginia Commonwealth University Seda VATANSEVER Department of Histology and Embryology, Celal Bayar University Semih AYDOĞDU Department of Orthopedics and Traumatology, Ege University Vasıf HASIRCI Department of Biological Sciences, Middle East Technical University Yannis MISSIRLIS Department of Mechanical and Aeronautical Engineering, Patras University Yuanyuan ZHANG Wake Forest Institute for Regenerative Medicine (WFIRM) x

17 PS2 PLENARY SPEAKER S ABSTRACT All The Appropriate Signals Are Necessary For Engineering Proper Tissues Yannis Missirlis 1 Patras University, Department of Mechanical and Aeronautical Engineering The highly interdisciplinary area of tissue engineering, by its nature, involves several fields of research from basic materials development to stem cell handling to clinical applications. While the need for quick applications is driven by necessity we are still far away from understanding how the hybrid system of material scaffolds-cellsbiomolecules operates optimally either in-vitro (in a bioreactor) or in-vivo. In our effort to monitor some basic responses of particular cells to specific environments we have developed a bioreactor able to supply a multitude of mechanical cues, singly or in combination to endothelial cells. In this presentation we will provide evidence of the importance of substrate stretching and frequency of stretching, of the shear rate of the flowing feeding medium on top of the cells, and of a simulated microgravity environment, especially by combining all these signals to the morphological adaptation of the cells and the rearrangement of its cytoskeletal proteins for each particular adaptation. 1

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21 O-BM01 Better Implants With Proper Design Of Processing And Surfaces Vasıf Hasırcı METU, Department of Biological Sciences, Ankara 06800, Turkey BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800, Turkey Keywords: tissue engineering, nanopatterns, micropatterns, implant, surface Introduction: The bulk and surface properties of implants are or have to be significantly different. They are important because the success of the implant performance is determined by these. The biological world presents us some clues as to how we should modify our surfaces to achieve certain properties and one can mimic them to obtain better implants (those which can integrate better or do not attract bacteria) ad also these are very important in the tissue engineering studies. For example the relation between tissue engineering scaffold surface properties and cell and tissue adhesion is critical especially in the early stages of their encounter. These surfaces could be modified through creation of micro and nano-sized physical and/or chemical patterns. Figure 1 shows two such surfaces one in the form of accurately reproduced wells and the other protruding rods transferred onto polymeric films. The way cells attach is the other important parameter in the cell-material interactions. The response of the cells can be observed and even quantified by measuring rates of adhesion, proliferation and differentiation and also measurements of deformation of the cell and nuclei. Studies indicate that cues with certain dimensions are more prone to cause cell adhesion, whereas some others cause their orientation while others lead to bending of the nuclei. Discussion & Conclusions: Surface cues are very important and very useful tools in creating optimum implants and they seem to have the potential to make growth factors useless. Fig 1. Physical cues on a polymeric surface: a) square wells, b) square rods Fig. 2 Cell shapes change on a surface patterned with square prism pillars. Saos2 human osteosarcoma cells on PLGA surfaces with micron sized pillars. (from H. Ozcelik's PhD thesis, METU, Ankara Turkey, 2012) otograph 5

22 O-BM02 Controlling Neural Cell Behavior at Biomaterial Interfaces Aylin Şendemir Ürkmez * Ege University, Departments of Bioengineering, Biomedical Technologies, Materials Science and Engineering, Center for Brain Research, Izmir, Turkiye Keywords: Biomaterials, neural cells, scaffold Introduction: As the world population ages, there is an increasing need for alternative therapies for neurodegenerative diseases such as Alzheimer s and Parkinson s diseases. Regenerative capacity of neural tissue is very limited after trauma or neurodegenerative diseases. Neural tissue engineering is considered as an alternative treatment method for regeneration of central nervous system (CNS). But the difficulties of maintaining neural tissue in vitro impose investigation of alternative materials and methods. Surface chemistry and the microstructure of the scaffolds, biochemical microenvironment, as well as mechanical and electrical cues are shown to effect neural cell behavior on different biomaterials and for the scaffold-cell interactions. For example, fibrous scaffolds resembling the extracellular matrix, which is the cells natural microenvironment are reported to receive higher success rate in neural tissue engineering applications. Alignment lead cells to attach in a bipolar morphology and parallel to the fibers [1,2]. Similarly, mechanical stresses exerted on neural cells as well as electro-magnetic fields were shown to effect nerve regeneration and neurite extension in vivo and in vitro. Effects of loading are very complicated since until a threshold, mechanical tension plays a positive role while after the threshold value, it is degenerative [3-5]. This presentation will give a brief review of the effects of different factors on neural cell behavior on biomaterials from the literature, with emphasis on the experiences of Ege University Animal Cell Culture and Tissue Engineering (EgeREACT) Laboratories. Discussion & Conclusions: A thorough investigation of neural cell behavior on biomaterial interfaces will help to fight the neurodegenerative diseases that are important threats for human health and life quality by providing effective in vitro models of neurodegenerative diseases and by allowing cultivation and growth of neural cells in vitro for tissue engineering purposes. Acknowledgements: This work is partially funded by The Scientific and Technological Research Council of Turkey (TUBITAK), E.U. Scientific Research Coordination Unit (BAP) and E.U. Science and Technology Center (EBILTEM). [1] F. Yang, R. Murugan, S. Wang & S. Ramakrishna. (2005). Biomaterials 26: [2] E. Verdu, R. O. Labrador, F. J. Rodriguez, D. Ceballos, J. Fores & X. Navarro. (2002). Restorative Neurology and Neuroscience 20: [3] T. Wang, J.S. Forsythe, D.R. Nisbet & C.L. Parish. (2012). Biomaterials 33(36): [4] J.E. Collazos-Castro, J.L. Polo, G.R. Hernández- Labrado, V. Padial-Cañete & C. García-Rama. (2010). Biomaterials 31(35): [5] F.R. Bueno & S.B. Shah. (2008). Tissue Engineering B14(3):

23 O-BS01 Biosensors: Past, Present and Future Mustafa Kemal Sezgintürk Namık Kemal University, Tekirdağ, TURKEY Keywords: Biosensing, biosensor, lab-on-a-chip, nanotechnology, point-of-care devices Author Phot ograph r Introduction A biosensor is a self-contained integrated device that is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element which is in direct spatial contact with a transduction element. In general, a typical biosensor is composed for five parts (I) bioreceptors that bind of specific form to the analyte; (II) an electrochemically active interface where specific biological processes occur giving rise to a signal; (III) a transducer element that converts the specific biochemical reaction in an electrical signal that is amplified by a detector circuit using the appropriate reference; (IV) a signal processor (e.g. computer software) for converting the electronic signal to a meaningful physical parameter describing the process being investigated and finally, (V) an proper interface to present the results to the human operator. Currently, the biosensors can be applied to a large variety of samples including body fluids, food samples, cell cultures and be used to analyze environmental samples. Discussion & Conclusions In 1956 Professor Leland C. Clark publishes his paper on the development of an oxygen probe and based on this research activity he expanded the range of analytes that could be measured in 1962 in a conference at a Symposium in the New York Academy of Sciences where he describes how to make electrochemical sensors more intelligent by adding enzyme transducers as membrane enclosed sandwiches [1] The first example was illustrated by entrapping the Glucose Oxidase in a dialysis membrane over an oxygen probe. Recent advances in biochemistry, molecular biology, and immunochemistry have expanded the range of biological recognition elements, improving assay selectivity and sensitivity, while the advent of diode lasers and LEDs has enabled the development of small, inexpensive optical biosensors. In addition, developments in fiber optics and microelectronics have yielded signal transducers that are smaller and more durable, and which offer improved signal/noise ratios and reduced manufacturing costs. The most common biosensors on the market are enzyme- or antibody-based. However, many research laboratories and commercial companies are now developing DNAbased biochip arrays geared specifically toward genomic studies and drug development. Some researchers are also working to affix entire living cells to a chip[2]. For the biosensor to be of optimal use, it must be at least as precise and standardized as other available technology. Personnel with minimum training should be able to use these devices. In addition to sensitivity, simplicity and fast processing power, micro fabrication technology enhances biosensors with desired specifications. The level of sophistication, awareness, cost, reliability, availability and marketing are all factors involved in deciding, whether biosensors would become popular in near future[3]. [1] Grieshaber, D., et al. (2008) Sensors 8(3), ) [2] Brown, M., (2010) Chemistry World 7 (1), [3] Iost, R.M., et al. (2011) Frontiers Biosci. 3,

24 O-BS02 Nanomaterials Integrated Electrochemical Biosensor Technologies Arzum Erdem Ege University, Faculty of Pharmacy, Analytical Chemistry Department, Bornova, Izmir TURKEY Keywords : Electrochemical Biosensor, Nanomaterials, Electrochemistry, Sensor The progress of advanced biosensor technologies could impact significantly in the areas of genomics, proteomics, biomedical diagnostics and drug discovery [1-3]. Electrochemical biosensors coupling the inherent specifity of biorecognition reactions with the high sensitivity of physical transducers, hold great promise for the detection of nucleic acids, proteins, toxins for clinical, environmental, or forensic investigations [1,2,4]. The nanoscale materials integrated biosensors based on nanotubes, nanoparticles, dendrimers, nanorods, nanowires, and other nanomaterials have recently received the considerable attention [1-5]. An overview to the electrochemical biosensor technologies combined with different types of nanomaterials have been presented herein for monitoring of spesific biomolecular recognitions; such as, nucleic acids, aptamer-protein, or drug- DNA interactions with their advantages and further applications. Acknowledgements. A.E acknowledges the financial support from Turkish Scientific and Technological Council (TUBITAK Project no. 106S181 and 111T073), and she also would like to express her gratitude to the Turkish Academy of Sciences (TUBA) as the associate member of TUBA for its partial support. 1- E. Palecek, M. Bartosík (2012) Chem. Rev. 112: J. Wang (2005) Electroanalysis 17: P.M. Dean, E.D. Zanders, D.S. Bailey (2001) Trends in Biotechnology 19: A. Erdem (2007) Talanta 74: F. Patolsky, C.M. Lieber (2004) Materials Today 8: 20. Acknowledgements. A.E acknowledges the financial support from Turkish Scientific and Technological Council (TUBITAK Project no. 106S181 and 111T073), and she also would like to express her gratitude to the Turkish Academy of Sciences (TUBA) as the associate member of TUBA for its partial support. 8

25 O-BMI01 Biomedical Visualisation Merve Evren Ege University, National and Applied Sciences, Department of Biotechnology, İzmir, Turkiye Keywords: 3D animation, biomedical visualisation, computer graphics, illustration, medical imaging Introduction: Biomedical visualisation is a visual representation that is the result of art skills expressed in a tangible or virtual medium that conveys medical or biological information, performed by biomedical illustrators and animators. The field is changing rapidly due to discoveries in both science and technology. From the human genome to the latest robotic surgical technique, the need for accurate effective communication continues to expand. Advances in computer graphics and imaging are generating vast new opportunities in which visualization is the key to understanding. Subcellular processes too small to be seen even by the most advanced microscopes can come alive through computer animations. A growing need for patients to better understand their state of health and their medical options is expanding the production of medical information aimed at the lay public. [1] A biomedical illustrator-animator is a professional artist with advanced education in both the life sciences and visual communication. Collaborating with scientists, physicians, and other specialists, medical illustrators transform complex information into visual images that have the potential to communicate to broad audiences. Fig. 1. Examples of 3D modelling and 2D illustration work of medical illustrations Discussion & Conclusions: This presentation includes examples of medical illustration and animation, construction stages and the current status in the world and Turkey. [1] Association of Medical Illustratiors Source Book 9

26 O-RM01 Biomimetic Tissue Engineering In A Bioreactor With Adipose Mesenchymal Stem Cells Y. Murat Elçin* Ankara University, Department of Biochemistry, Turkey Keywords: 10

27 O-RM02 Clinical Potential Use Of Differentiated Cells From Embryonic Or Mesenchymal Stem Cells H. Seda Vatansever Celal Bayar University, Faculty of Medicine, Department of Histology- Embryology, Manisa, TURKEY Keywords: Clinical trials, embryonic stem cells, differentiation, mesenchymal stem cells Introduction: Stem cells are classified by their source and the tissue. They are typically generated such as embryonic stem cells, fetal stem cells and somatic (adult) stem cells. Embryonic stem cells are derived from inner cell mass of blastocyst stage of embryos and are remain proliferative in an undifferentiated or differentiated conditions. Mesenchymal stem cells can be isolated from tissues such as bone marrow, fat tissue etc. After improving of culture condition and differentiation potentials, differentiated stem cells are choosing as a first cells using in modern regenerative medicine and tissue engineering. Aims: My studies focused on both embryonic and mesenchymal stem cells culture, differentiated them to other somatic cells and analyze in vivo adaptation and treatment potentials. Methods: Embryonic stem cells were cultured on STO feeder layer and differentiated them hanging drop technique. They were differentiated to neuron, keratinocytes and endotel cells. After experimental animal models, they were transferred and analyzed in vivo adaptation and treatment potentials. Mesenchymal stem cells were obtained from bone marrow or adipose tissue. Undifferentiated or undifferentiated bone marrow stromal mesencymal cells were transferred into experimental animal models and evaluated their function in vivo. Adipogenic stem cells were cultured in differentiated condition and were also transferred in animal to analyze their treatment potentials. Results: While differentiated potentials of embryonic stem cells were clearly visible when compared to mesencyhmal stem cells, their ethical problems and risk of teratoma, suggests the use of mesenchymal stem cell. Discussion & Conclusion: Because of stem cell sources and differentiation potentials to other somatic cells, for cell based therapy, their using may depend on disease and tissue engineering technique. [1] Vatansever HS, Uluer ET, Aydede H, Ozbilgin MK, (2013). Analysis of transferred keratinocytelike cells derived from mouse embryonic stem cells on experimental surgical skin wounds of mouse. Acta Histochem. 115(1): [2] Deliloglu-Gurhan SI, Vatansever HS, Ozdal-Kurt F, Tuglu I.(2006). Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system. Acta Histochem, 108(1): [3] Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, Edgar D. (1999). Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol. 11;144(1):

28 O-TM01 Bridging The Gap - Skeletal Stem Cell Based Strategies For Bone Regeneration Richard O C Oreffo * Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK Keywords: Bone Regeneration, Skeletal Stem Cell, Translational Medicine Abstract: Regenerative medicine strategies have sought to repair skeletal defects resulting from trauma and disease with the application of cells, typically isolated from the patients themselves, in combination with porous biomaterials or scaffolds. Advances in our understanding of skeletal stem cells and their role in bone development and repair, offer the potential to open new frontiers in bone regeneration. We have developed protocols for the isolation, expansion and translational application of skeletal populations, including enriched skeletal stem cell populations for skeletal repair [1] with cues from developmental biology and the application of nanotopographical cues and architecture to modulate stem cell fate. A number of areas of work will be presented including: i) isolation and characterisation strategies for fetal and adult skeletal populations, iii) translational studies to examine the efficacy of skeletal populations for orthopaedic application. Advances in our understanding of skeletal stem cells and their role in bone development and repair, offer the potential to open new frontiers in bone regeneration and offer exciting opportunities to improve the quality of life of many. Acknowledgements Funding from the BBSRC, MRC and EU FP7 (Biodesign) is gratefully acknowledged. [1] Dawson JI, Kanczler J, Tare R, Kassem M, Oreffo ROC Author(s). (2013). Stem Cells. Bridging the gap: Bone regeneration using skeletal stem cell-based strategies - Where are we now? doi: /stem [Epub ahead of print] ii) derivation of niche environments through combination of progenitor cells with tailored nanotopographical strategies / architecture to modulate the osteogenic and angiogenic repair process and, 12

29 O-TM02 Biomaterials In Orthopaedics: More Problems Than Benefits? Semih Aydoğdu Ege University Hospital, Department of Orthopaedic Surgery, Izmir, TURKEY Keywords: Arthroplasty, biomaterials, implant, orthopaedics Introduction: During the last five decades biomaterials have been progressively in use and diversified a lot in orthopaedic practice. Approximately in %80 to 90 of all orthopaedic surgeries at least one biomaterial is used. In 2012, cardiovascular biomaterial market contributed almost 35% of all biomaterials market and followed by orthopaedic segment. The global market for biomaterials in 2012 is estimated at $44 billion and is expected to reach $88.4 billion by North America is actually the largest market, but in coming years due to rising awareness, it should be expected that Asia could have an increasing share in the market even the largest [1]. At the beginning biomaterials in orthopaedics have been used as only a fixation material. But in time, it has been to possible to use them as replacement, support, carrier and regenerative materials. For a long time period, only metals and mainly stainless steel were the unique biomaterial used by orthopaedic surgeons. In last three decades both cobalt-chromium alloys and titanium alloys with different material properties and biological tissue responses have got a significant place in metallic biomaterials chosen. Polymer-based biomaterials have been also in use for long time frequently in association with metallic biomaterials. Polymethylmetacrylate and polyethylene are the first examples used by orthopaedic surgeons since the beginning of the joint replacement surgeries. In last decades recent developments in tissue engineering have expanded the role of biomaterials for regenerative purposes as well. Different polymers are currently in use as cartilage tissue repair materials (scaffolds) and for biodegradable fixation of bone and soft tissues. Fig. 1. Metallosis as a sign of failed knee joint replacement. Ceramics have also been in use largely particularly in joint replacement surgeries for their high wearresistance characteristics and as a surface treatment material for their high osteoconductive properties (such as hydroxyapatite). But despite enormous development and research, orthopaedic surgeons sometimes face biomaterialrelated problems; in the form and structure of biomaterial itself (wear, corrosion, break, failure,..) or in bonding / fixation of biomaterials with the local biologic tissues (loosening) (Figure 1). Discussion & Conclusions: Although it has not been possible completely replicate the form and function of biological tissues, biomaterials help to solve numerous problems of musculoskeletal system; but their use can produce new and specific problems as well. : [1] Reports/biomaterials-393.html 13

30 O-AO01 Development of the First Turkish Axial-flow LVAD and its Hemodynamic Testing Platform Kamuran A. Kadıpaşaoğlu*, Erol M. Sezer Bahçeşehir University (BAU), Istanbul, Turkey Keywords: CFD, Hemodynamics, LVAD, Mock Circuit, PIV Introduction: Left ventricular assist devices (LVADs), which are rotary pumps providing continuous and pulseless flow, unload the failing ventricle and reduce mortality and morbidity of patients on the transplant waiting list. The reduction of the arterial pulse associated with the unloading is thought to have coagulopathic sequalae. Artificial undulation of pump speed has already been proposed, although its optimal modality is presently unknown. In our country, LVADs are not being produced and limited number of pumps are imported at high costs with dismal outcomes, making LVAD R&D a national necessity. Methodology: An axial-flow LVAD Development Program has been initiated in 2009 at BAU, and funding was obtained in 2011(TÜBİTAK 1001). An original prototype has been developed in SolidWorks and its hemodynamic performance was tested using Computational Fluid Dynamics (CFD). A motorless physical prototype was built based on the virtual concept, along with a speed-undulating control algorithm. In parallel, a physical time-varying left ventricular elastance-driven feedback-controlled CV mock circuit was modeled, built and operated in normal and heart failure modes. Progress: The Program is currently in the process of moving from the virtual to the physical phase thanks to a second grant (also TÜBİTAK 1001). An external drive mechanism is designed and built to connect the motorless prototype to the mock circuit run in heart failure mode. Physiologic (Pressure-flowvolume in mock circuit) and optic (flow velocity and shear stress fields in the prototype by Particle Image Velocimetry- PIV) performance tests will be done. Thus 1) virtual and physical performance test outcomes will be compared and LVAD geometry optimized through CFD-PIV iterations and 2) optical field data will be combined with pressureflow measurements for various operational modalities of the LVAD in order to optimize and validate the Control Algorithm. Discussion: The Project is part of the first program in Turkey to develop an original, effective and competititive axial-flow LVAD for world and national markets. The pump design is original and patentable. The Project is asking the hitherto unanswered question of optimal LVAD operation modality using induced pulsation of the rotor speed. Control Algorithm developed is based on keeping the aortic valve open at intervals while attaining a minimum mean arterial pressure. The CV mock circuit is designed to incorporate a novel hybrid control based on LV elastance and auto-regulation of the heart rate via diastolic time constant (compliance and resistance) of the aorta. Comments: The Project will mobilize technological and scientific potential of our country in developing very high-tech medical products, and recruit effificient Academia, Hospital and Industry collaboration. 14

31 O-AO02 Artificial Organs and Blood Interaction: Haemorheological Aspects Khosrow Mottaghy Institute of Physiology, RWTH Aachen University, Germany Keywords: Artificial internal organs, Haemocompatibility, ECC, Coagulation. Introduction : Artificial organs as medical devices are presently an important topic in the field of Biomedical Engineering with a rapid growth of research and industrial production. They can be implanted or integrated into and also applied extracorporeal in order to support partially or even replace totally the natural organs. The common property of the artificial internal organs is however, their direct contact with blood i.e. contact with different biomaterials possessing various surface areas, depending their selection and suitability for specific functions, and different blood flow rates and properties toward these surfaces. Long term support of sever diseased internal organs such as heart, lung, kidney and liver enhance even more the challenge to maintain the physiological functioning of blood and reduction of trauma. Here will be discussed the common and specific blood rheological properties of typical artificial organs integrated to extracorporeal circulations in regard to blood trauma considering the biomaterials effective surface modification for the improvement of haemocompatibility. However, the tests of efficiency of different surface modification methods should be still improved in order to be able to have definitive results especially about their durability of their efficacy. This is an important issue for possible clinical use especially for long-term application. Acknowledgements: I would like to thank all my PhD students who have contributed with their excellent work and research in the field of extracorporeal circulation in the ECClab-research group inside the department of physiology. Discussion & Conclusions: In the recent years much progress is obtained to improve the haemocompatibility of different types of biomaterials. This has been accompanied by introduction of several surface modification methods to enhance the haemocompatibility. 15

32 O-TM07 Cancer and Stem Cell Gülperi Öktem Ege University Medical Faculty Department of Histology and Embryology Ege University Health Science Institute Department of Stem Cell Keywords: Cancer, stem cell, asymmetric division, plasticity, spheroids The maintenance and repair of many adult tissues are ensured by stem cells (SCs), which reside at the top of the cellular hierarchy of these tissues. Functional assays, such as in vitro clonogenic assays, transplantation and in vivo lineage tracing, have been used to assess the renewing and differentiation potential of normal SCs. Similar strategies have suggested that solid tumours may also be hierarchically organized and contain cancer SCs (CSCs) that sustain tumour growth and relapse after therapy [1]. Tumors consist of a complex and heterogeneous phenotypic population and comprise the arrangement of different cell types. More specifically, within tumor mass, rare group of cancer cells that persist within the bulk of human tumors that are capable of serving cancer- initiating cells or cancer stem cells (CSCs) [2,3]. Correlatively with normal stem cells, CSCs undergo asymmetrically cell division, giving rise to one daughter cell that becomes a committed progenitor. In this complicity, CSCs give rise to a hierarchy of actively proliferating, but progressively differentiating cancer cells, which contribute to the cellular heterogeneity of human cancers [4]. This cells which are able to selfrenew and differentiate are not only the potential origin of the tumor, but also the possible source of recurrence and chemo-resistance [5]. Recent studies have supported this proposal and suggest the utility of several factors to induce the differentiation of cancer stem cells [6]. The demonstration that metastatic sites have heterogeneous histological characteristics suggests that the cells capable of undergoing this process have the ability to self-renew as well as differentiation properties that are unique to cancer stem cells (CSCs) [7]. Established cancer cell lines contain CSCs, which can be propagated in vitro using defined conditions, to form 3D tumor spheroids [8]. The in vivo cellular microenvironment is regulated by a complex interplay of soluble factors and signaling molecules secreted by cells and it plays a critical role in the growth and development of normal and cancer tissues. [1]Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res Mar;22(3): [2] Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res Sep 15;63(18): Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer stem cells. Int J Biochem Cell Biol Dec;44(12): [3]Neumüller RA, Knoblich JA. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev Dec 1;23(23): Review. [4] La Porta CA. Mechanism of drug sensitivity and resistance in melanoma. Curr Cancer Drug Targets May;9(3): Review. [5]Yin G, Alvero AB, Craveiro V, Holmberg JC, Fu HH, Montagna MK, Yang Y, Chefetz-Menaker I, Nuti S, Rossi M, Silasi DA, Rutherford T, Mor G. Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential. Oncogene Feb 20. [6] Hurt EM, Chan K, Serrat MA, Thomas SB, Veenstra TD, Farrar WL. Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation. Stem Cells Mar 31;28(3): [7] Robertson FM, Ogasawara MA, Ye Z, Chu K, Pickei R, Debeb BG, Woodward WA, Hittelman WN, Cristofanilli M, Barsky SH. Imaging and analysis of 3D tumor spheroids enriched for a cancer stem cell phenotype. J Biomol Screen Aug;15(7):

33 O-RM06 Human Urine-Derived Stem Cells: Biological Characterization and Potential Cell-Based Therapy Yuanyuan Zhang Wake Forest University, Institute for Regenerative Medicine, Winston-Salem, NC, USA Keywords: stem cells, regeneration, urine, urology Tissue-specific stem cells and/or progenitor cells exist in almost every tissue and organ of the body. These cells differ from somatic cells by their ability to differentiate into the many types of cells required for tissue maintenance, repair, and regeneration. As these stem cells are a very small subpopulation of cells, they are difficult to isolate from most differentiated somatic cells present in the tissues and organs. To obtain these stem cells often requires invasive tissue biopsy. Therefore, a stem cell source that could be obtained via a non-invasive approach would be highly desirable. We recently found that a subpopulation of cells isolated from human voided urine possess characteristics similar to mesenchymal stem cells (MSC) in clonogenicity, cell growth patterns, expansion capacity, cell surface marker expression profiles, and multi-potent differentiation capacity. These urine-derived cells are positive for the MSC surface markers CD24, CD29, CD44, CD54, CD73, CD90, CD105, CD146, and CD166, but do not express markers associated with hematopoietic stem cells. In addition, these urine-derived cells also express some embryonic stem cell markers, including Oct4, c-myc and klf4. Stem cells derived from urine are capable of multi-potent differentiation to endothelial, osteogenic, chondrogenic, adipogenic, myogenic and neurogenic lineages. Generate a large number of cells from a single clone. About 50-75% of the cells collected from middle-aged individuals expressed telomerase activity and retained long telomere lengths. The cells with telomerase activity possessed higher proliferative capacities and could be maintained for up to 67 population doublings (PD), indicating that a single USC clone can generate 2 67 (i.e. 1.5x10 20 ) cells within 14 weeks, compared to 35 PD (2 35, i.e. 3.4x10 10 cells) for USCs that do not express telomerase. After several passages, the cultured cells displayed normal chromosomes and no teratomas formed during the 3-month in vivo study. After refining the cell isolation methods used to obtain USCs, up to 140 USC clones/24 hours urine can be consistently obtained from each individual. One 200-ml urine sample can provide enough cells at the early passages to create a piece of cell-seeded scaffold (about 4 x 5cm3 in size) for bladder or urethra regeneration. In conclusions, USCs could be a viable cell source that can be collected using a simple, safe, low-cost, and non-invasive procedure for re-engineering urethral or bladder tissues, as well as treating kidney diseases, erectile dysfunction, stress urinary incontinence, vesicoureteral reflux, or other diseases that are suitable for regenerative medicine and tissue engineering applications, in urology and other fields as well. These urine-derived stem cells (USCs) can generate a large number of cells from a single clone. About 50-75% of the cells collected from middle-aged individuals expressed telomerase activity and retained long telomere lengths. The cells with telomerase activity possessed higher proliferative capacities and could be maintained for up to 67 population doublings (PD), indicating that a single USC clone can generate 2 67 (i.e. 1.5x10 20 ) cells within 14 weeks, compared to 35 PD (2 35, i.e. 3.4x10 10 cells) for USCs that do not express telomerase. After several passages, the cultured cells displayed normal chromosomes and no teratomas formed during the 3-month in vivo study. After refining the cell isolation methods used to obtain USCs, up to 140 USC clones/24 hours urine can be consistently obtained from each individual. One 200-ml urine sample can provide enough cells at the early passages to create a piece of cell-seeded scaffold (about 4 x 5cm 3 in size) for bladder or urethra regeneration. Discussion & Conclusions : In conclusions, USCs could be a viable cell source that can be collected using a simple, safe, low-cost, and non-invasive procedure for re-engineering urethral or bladder tissues, as well as treating kidney injures or diseases, erectile dysfunction, stress urinary incontinence, vesicoureteral reflux, or other diseases that are suitable for regenerative medicine and tissue engineering applications, in urology and other fields as well. 17

34 O-BM06 New Approaches in Designing Antibacterial Polymeric Surfaces Kezban Ulubayram 1,2,3 1Department of Basic Pharmaceutical Sciences/Faculty of Pharmacy, 2Graduate Department of Nanotechnology and Nanomedicine, 3Graduate Department of Bioengineering/Institute of Graduate Studies in Science, Hacettepe University, Turkey graph Keywords : Medical device infections, antibacterial polymeric surface, polymeric brushes Introduction: Biomaterial based infections are most frequently encountered major problems after the operation and can be seen in almost every type of medical device regardless of the implantation site. Along strict manufacture, storage and application processes, bacterial invasion may occur via intrinsic or extrinsic pathways such as operational, environmental or patient related ones. Antibiotics are still gold standard for an efficient therapy against bacteria. However the infections must be treated as early as possible to avoid any systemic infection or a possible implant failure. Also systemic use of antibiotics in treatment of infections caused by these microorganisms has been ineffective due to bacterial resistance development. Since bacteria can develop a resistance against drugs by building up a thick and dense structure called biofilm in a few days, a rapid solution is essential for the treatment [1]. To conquest the fight against bacteria it is possible to endue a characteristic on biomaterial which has the ability to prevent surface adhesion of bacteria. Various surface coatings for biomaterials have been developed in an attempt to prevent infections; most of them work by incorporating and releasing such bactericidal agents as silver ions, quaternary ammonium salts, triclosan, antibiotics, enzymes or other drugs that leach into the environment [2]. The drawback of these approaches is that the smallmolecule antimicrobial agents eventually will be exhausted, leading to limited functional lifetimes. As a result of clinical importance of infection, there is a considerable demand to develop stable nonleaching antimicrobial surfaces that are required for long term protection against bacteria [3]. Recently, antimicrobial synthetic polymers have gained much popularity owing to the permanent antimicrobial activity. Especially; cationic compounds are promising candidates materials for antibacterial applications. Since all the techniques aim quite the same goal prevention of adhesion - the mechanism of action may differ for various types of applied biomaterials. In this presentation, the ongoing studies of our research group on the development of antibacterial polymeric surfaces will be discussed. Acknowledgements: This work is financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK)(Grant no: 112M293). [1] An Y.H., Friedman R.J. (1998). J. Biomed Mater. Res. 43: [2] Wong S.Y., Li Q. et al. (2010). Biomaterials 31(14): [3] Tiller J.C., Liao C.J. et al. (2001). Proceedings of the National Academy of Sciences of the United States of America 98(11):

35 O-CB01 Universities as Engines of Wealth Creation: Rethinking the Commercialization Model Russell D. Jamison, Ph.D. Virginia Commonwealth University, Richmond, Virginia, USA Keywords: technology transfer, innovation, entrepreneurship, invention, commercialization Introduction: As innovation has become a key driver of economic success in a global economy, research universities are increasingly viewed as essential providers of both invention and talent. Traditional models of technology transfer from universities to the private sector are inadequate for achieving this goal. Linear models of laboratory discoveries leading to patents then to licenses, do not account from a number of less formal mechanisms that create richer pathways to wealth creation from academic research investments. This presention briefly reviews current practices in U.S. university techology transfer offices and describes an alternative model that views the universities as simply one element in an interdependent innovation ecosystem. Discussion & Conclusions: The U.S. federal government provides $90 billion each year to support research conducted in universities. 1 By law, universities claim and benefit financially from intellectual property resulting from this federallyfunded research. However, many university technology transfer offices continue to experience difficulty in realizing significant return on this government investment. This is in part because of an over-emphasis on patents as the essential product of faculty research. While patents and the licensing income they can produce are directly measurable, they reflect a focus on outputs rather than outcomes. The fact that a handful of universities have benefited enormously from valuable inventions (often drugs) has caused university administrators to expect similar results. Data simply do not support this expectation. 1 Fig. 1. University technology transfer exists as one element of an innovation ecosystem. A more effective technology strategy recognizes the importance of continuous, informal engagement of university faculty and their graduate students with potential private sector partners. 2 This model emphasizes academic entrepreneurship and open innovation. Such a model requires a change in the reward system for university faculty that recognizes the value of commercialization of research, and a change in the expectations of private sector partners who themselves have reward systems that foster impatience and short-term investment. : [1] West, D. (2012). Improving University Technology Transfer and Commercialization, Issues in Technology Innovation, No. 20, pp [2] Bradley, S., Hayter, C, and Link, A. (2013). Models and Methods of University Technology Transfer, Foundations and Trends in Entrepreneurship, Vol. 9, No. 6, pp

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39 O-BM03 Electrospun PEO nanofiber coated titanium surfaces Murat Şimşek *,1, Sevcan Dalkıranoğlu Aldemir 2, Menemşe Gümüşderelioğlu 1,3 Hacettepe University Department of Nanotechnology and Nanomedicine 1, Biology 2 and Chemical Engineering 3, Ankara, Turkey * Keywords: electrospining, nanofiber, polyethylene oxide, S. epidermidis, titanium implant Introduction: Titanium (Ti) and its alloys have been extensively used as implant materials in orthopedic and dental applications because of their excellent properties. Nevertheless, implants may cause some bacterial (such as S. epidermidis) infections [1]. In this regard, recently effort has focused on the development of anti-infective implant surfaces based on the modification of the physicochemical properties. In this study, titanium surfaces were coated with polyethlene oxide (PEO) nanofibers by using electrospinning method and than bacterial/cellular adhesion was evaluated on these surfaces. Methods: Ti surfaces were coated with PEO nanofibers by using electrospinning method. In order to achieve insoluable coatings, PEO fibers were crosslinked by UV radiation in the presence of photocrosslinker, pentaerythritol triacrylate. Finally, animal cell and bacteria cultures were carried out with fibroblastic MC3T3-E1 preosteoblasts and S. epidermidis to evaluate cellular attachment on these surfaces. Results: PEO nanofibers on Ti surfaces had an dimater of nm (Fig. 1). Bacteria/cell culture studies showed that attachment of S.epidermidis and MC3T3-E1 cells on coated surfaces was significantly lower than that of uncoated ones through culture period (Fig 2). Figure 1. a) SEM and b) AFM images of PEO nanofibers on Ti. a 5 µm Figure 2. SEM images of S. epidermidis on (a) pure Ti and (b) coated Ti surfaces after 24 h of incubation. Discussion & Conclusions: In conclusion; i) Ti implants were coated by electrospining easily ii) Stable PEO coating was obtained by crosslinking with PETA. iii) PEO-coated Ti surfaces significantly reduced the bacterial/cellular attachment without the need for any other modifications. Besides Ti surfaces is resistant to bacterial attachment, it is also expected that they promotes osteointegration in terms of materialtissue compliance. Our further studies will focus on this topic in order to encourage cellular adhesion for tissue-implant integration. [1] Koon Gee Neoh, Xuefeng Hu, Dong Zheng, En Tang Kang. (2012). Biomaterials 33: b 2 µm 23

40 O-BM04 Nanotoxicity of SnO2 and ZnO nanoparticles in human periodontal ligament fibroblast and mouse dermal fibroblast cells Şükran Şeker 1,2, A. Eser Elçin 1,2, Tuğrul Yumak 2, Ali Sınağ 2, Y. Murat Elçin *,1,2 1 Ankara University Stem Cell Institute, Ankara, Turkey 2 Ankara University Faculty of Science, Ankara, Turkey * Keywords: Fibroblast cells, hydrothermal method, metal oxide, nanoparticles, toxicity Aim: The aim of this study was to investigate the in vitro cytotoxicity of hydrothermally synthesized SnO 2 and ZnO nanoparticles (NPs) on human periodontal ligament fibroblast (hpdlf) and mouse dermal fibroblast (mdf) cells. Introduction: The unique size-dependent properties of nanomaterials make them very attractive for potential applications within the biomedical, commercial and environmental sectors [1]. Metal oxide NPs have been widely used in nanotechnology-based industries, namely catalysis, sensors, and environmental remediation, and for their incorporation into commercial products. Despite many benefits of nanotechnology, a wide range of studies indicate the potential hazards of certain NPs on humans and the environment because of their small size and unique properties [2]. Many types of NPs have proven to be toxic to human tissue and cell cultures. Therefore, it is impotant to evaluate the risk/benefit ratio of using NPs for any applications. Materials and Method: In this study, we have evaluated the potential toxic effects of SnO 2 and ZnO NPs on hpdlf cells and mdf cells in vitro. 3-4 nm sized SnO 2 and 7-8 nm sized ZnO NPs having uniform spherical shapes were successfully synthesized by the hydrothermal method. NPs were characterized using atomic force microscopy (AFM), Braun-Emmet-Teller (BET) analysis and dynamic light scattering (DLS). The hpdlf and mdf cells were incubated with sterilized NPs with concentrations of 0.1, 1, 10, 50 and 100 μg/ml for 6, 24 and 48 hours duration. For toxicity evaluations, cellular morphology, mitochondrial function, membrane leakage and were assessed under control and exposed conditions. The effects on cell morphology were evaluated using phase contrast microscopy and scanning electron microscopy. Transmission electron microscopy was also used to visualize the morphological changes and subcellular localization of NPs. Results and Discussion: The findings demonstrated that SnO 2 and ZnO NPs resulted in the cytotoxicity at the concentration dependent and time-dependent manner in fibroblast cells. The cells started to shrink and became irregular in shape at increasing concentration of NP compared to control cultures. Morphological images demonstrated that nanoparticles-exposed cells at higher doses became abnormal in size, and most of the cells were detached from the bottom of the cultured plates. Cytotoxicity of NPs was dependent on concentration, time and surface area of NPs. Results showed that ZnO NPs were more toxic than SnO 2 NPs to fibroblastic cultures. Acknowledgements: Ankara University Stem Cell Institute (Ankara, Turkey); Turkish Academy of Sciences (TÜBA; to YME). [1] V.E. Kagana, Y.Y. Tyurina et al Toxicol Lett [2] Y. Kohl, E. Gorjup, et al J Nanopart Res

41 O-BS03 Carbohydrate-sensitive microtransporters for isolating sugars and cells Filiz Kuralay 1,2, Sirilak Sattayasamitsathit 1, Wei Gao 1, Aysegul Uygun 1,3, Adlai Katzenberg 1, Joseph Wang*,1 1 Department of Nanoengineering, University of California San Diego, La Jolla, CA, United States 2 Department of Chemistry, University of Ordu, Ordu, Turkey 3 Department of Chemistry, Süleyman Demirel University, Isparta, Turkey Keywords: Carbohydrates, Cells, Nanomotors Introduction: This study details a poly(3- aminophenylboronic acid) (PAPBA)/Ni/Pt microtube engine coupling the selective monosaccharide recognition of the boronic acidbased outer polymeric layer with the catalytic function of the inner platinum layer. The boronic acid-based microengine itself provides the target recognition without the need for additional external functionalization. On-the-fly binding and transport of yeast cells (containing sugar residues on their wall) and glucose are illustrated. Methods: PAPBA-functionalized microrockets were prepared by controlling electrochemical polymerization in an aqueous acidic solution containing 3-aminophenylboronic acid (APBA), sodium sulphate and HCl. The electropolymerization was carried out at +0.9 V (vs. Ag/AgCl) using a charge of 0.6 C. Subsequently, a platinum-nickel alloy layer was plated at -0.5 V for 50 s, -1.0 V for 300 s (Pt-Ni alloy, mostly Ni) and V for 120 s (inner Pt layer) using a 1:1(v:v) mixed solution of a commercial platinum solution and a nickel plating solution. Results: Template electrodeposition of the PAPBA outer layer is used for monosaccharide recognition in the study [1]. PAPBA layer has been shown useful for capturing and transporting glucose and for binding and releasing yeast cells containing sugar residues on their wall. Fig. 1 illustrates the pick up yeast cells by the microrocket. The specificity of the microrocket to Fig. 1. Binding of yeast cells yeast cell is controlled using 5-fold excess of the urinary pathogen Staphylococcus aureus containing mannose in its cell wall. No binding was observed since the PAPBA layer is known to have a substantially higher affinity to glucose than mannose [2]. Discussion & Conclusions: The polymeric outer layer acts as the receptor recognizing the target biomolecule, eliminating the need for additional receptor functionalization steps. Acknowledgements: This work was supported by the U.S. Defense Threat Reduction agency. [1] F. Kuralay, S. Sattayasamitsathit, W. Gao, A. Uygun, A. Katzenberg, J. Wang. (2012). J. Am. Soc. 134: [2] X.-Y. Sun, B. Liu, Y.-B. Jiang. (2004). Anal. Chim. Acta 515:

42 O-BS04 An immunosensor for ultrasensitive detection of parathyroid hormone Çiğdem Sayıklı Şimşek 1, Münteha Nur Sonuç *,2, Mustafa Kemal Sezgintürk 1 1 Namik Kemal University Faculty of Science, Biochemistry, Tekirdağ Turkey 2 Namik Kemal University, School of Health Tekirdağ Turkey Keywords: biomarker, immunosensor, impedimetric biosensor, parathyroid hormone Introduction: PTH (parathyroidhormone) has been presented as a functional marker of vitamin D status largely due to overexpression of plasma PTH concentration is a recognized risk factor for osteoporosis [1]. Moreover, bony metastases from prostate cancer are a significant cause of morbidity and mortality. These metastases are commonly cause increased serum levels of PTH as calcium ions are transferred from serum into blastic bone [2]. Identification of membranes, biosensor characterization and fabrication could be monitored by electrochemical impedance spectroscopy (EIS), effectively. The aim of this study to fabricate a new impedimetric biosensor, based on the use of anti- PTH as a biorecognition element for the determination of PTH sensitively and selectively. Methods: A three-electrode system, consisting of a gold working electrode, a Ag/AgCl reference electrode and a Pt counter electrode were used. EIS and CV were applied to monitore binding events of biosensor. Anti-PTH was immobilized through covalent coupling with firstly 1-mercaptohexanol to introduce functional OH groups and next (3- Aminopropyl)triethoxysilane which formed a selfassembled monolayer on gold electrode. Glutaraldehyde was used as a crosslinking agent. To provide successful biosensor current all experimental parameters were optimized. Results: Fig 1A and B can be seen CV and EIS results of different layers of biosensor (bare electrode, immobilization steps, and binding of PTH). At optimal working, wide range of 1- mercaptohexanol and APTES concentration were studied.50 mm and 3.5% were determined as optimal values and applied overnight respectively Fig.1A and 1B. CV and EIS of different layers of biosensor Moreover, anti-pth concentration was optimized as 10 ng/ml. Linear ranges of biosensor was determined between 10 and 50 fg/ml. The interaction between the biosensor and parathyroid hormon was firstly investigated by a novel elecrochemical method, single frequency impedace analysis. To demonstrate the feasibility of the biosensor in practical analysis, the artificial serum samples were experienced and has good agreement. Discussion & Conclusions: This is the first biosensor system to detect PTH utilizng by anti- PTH. Optimized experimental conditions for the fabrication and operation of the biosensor were studied. The biosensor has exhibited good repeatability (with a correlation), and reproducibility. Acknowledgements: Scientific and Technological Research Council of Turkey (TÜBİTAK, Project number: 109 T 172). [1] A. Prentice, G. R Goldberg, and I. Schoenmakers (2008) Am J Clin Nutr 88 [2] G. G. Schwartz Cancer (2008) Epidemiol Biomarkers Prev 17(3)

43 O-BS05 Homocysteine biosensor by gold piezocrystales Ezgi Öztürk 1, Sabiha Demirci 1, Hakan Ayhan 1, Fatma Ayhan *,1 1 Muğla Sıtkı Koçman University, Faculty of Science, Chemistry Department, Biochemistry & Biomaterials Research Laboratory, Kötekli, Muğla, Turkey Keywords: Gold piezo crystal, Homocysteine, Quartz crystal microbalance (QCM), Surface Introduction: Homocysteine, which is a methionine amino acid derived amino acid is an important risk factor for vascular diseases so, its dedection by a rapid and cheap method is under investigation and is a research theme with gradually increasing importance. In the scope of the presented study, the object is to perform the real time detection of homocysteine by using Quartz Crystal Microbalance (QCM) method. QCM technique is used for quantitative and/or qualitative determination of some materials especially which are present in nano scale levels. The analysis lies on the micro gravimetric analysis where the specific compound attached to the surface of crystal capture the target compound. Discussion & Conclusions: Repeatability and sensibility of homocysteine biosensors are acceptable results. Gold piezo crystals are useable sensors for homocysteine dedection. The lowest concentrations (µm) were obtained with gold piezo crystals than silver piezo crystals. [1]Lee Y.G., Chang, K.S., (2005) Talanta 65: [2] Chen, K-S., Chen, S-C., Lin, H-R., Yan, T-R., Tseng, C-C., (2007) Materials Science and Engineering C 27: [3] Liu Y.C., Wang CM, Hsiung KP, (2001) Analytical Biochemistry; 299: Method: In this present study, each surface of gold piezo crystals was cleaned with piranha solution, dried and measured starting frequency. After the surface cleaning, cysteamine molecules were immobilized to surface, dried and measured frequency. Glutaraldehyde was immobilized, dried and measured frequency. Bovine serum albumin that was prepared different concentration (0, 2-1 mg/ml) was immobilized the activated surface of gold piezo crystals, dried and measured frequency. Bovine serum albumin immobilized gold piezo crystals interacted with homocysteine, dried and measured frequency. Result: Surface of gold piezo crystal was characterized with SEM (Scanning Tunneling Microscope). According to observed differences of frequency, the lowest concentration was obtained. 27

44 O-BMI02 The concept design of microrobot based surgery robot for the treatment of non-communicating hydrocephallus B.Oğuz Gürses *,1, S. Sabancı 1, H. Çevik 2, G.K. Özboduç 1, L. Çetin 2, M. Boztepe 1, Mehmet Sarıkanat 1, T. Turhan 1, Ö. Mermer 1, A. Baltacı 1 1 Ege University, Izmir, Turkey 2 Dokuz Eylül University, İzmir, Turkey Keywords : Electromagnetic Manipulation, Mechatronic Design, Microrobots Introduction: Cerebrospinal fluid (CSF) is a transparent fluid which circulates through subarachnoid space and works as a supporting medium to the brain. Hydrocephallus is a condition which is a consequence of problems in absorption, circulation or production of CSF. Non communicating hydrocephalus is the kind of hydrocephallus which occurs due to the circulation problems of CSF in subarachnoid space. Ventriculostomy is applied by vetricular catheter and supported by endoscopic vision. Endoscopic surgical intervention used in ventriculostomy operation may cause undesired conditions and complications in subarachnoid space, and even mortality can be a result of these complications. Miniaturization and micromechanical system technologies propose new solutions to such medical problems. Microrobots are submilimetric robots or particles and their movement on a desired trajectory can be controlled by external mechanisms. There are researches in cardiovascular, intraocular, gastrointestinal applications of microrobots[1]. In this study, a microrobot system which is controlled by an electromagnetic actuator for the treatment of non communicating hydrocephallus is proposed, and possible outcomes of this robotic system is investigated. A multipole electromagnetic actuator will be designed to generate necessary magnetic field to translate and orient the microrobot. Microrobot will be a permanent magnet based microstructure and has a unique morphology to apply necessary forces on the targets in subarachnoid space. Image based position and orientation recognition system will be used a sensor in closed loop operation of the system. An experimental setup will be designed for the in-vitro studies of the proposed system (Fig.1). Fig. 1. Experimental Setup of IAR Discussion & Conclusions: Untethered microrobot systems promise new opportunities for targeted drug delivery applications and surgical operations in neurosurgical problems. Acknowledgements: Financial support for this study was provided by TUBITAK-The Scientific and Technological Research Council of Turkey, Project Number: 111M182. [1] B. J. Nelson, I. K. Kaliakatsos, and J. J. Abbott, Annual Review of Biomedical Engineering, vol. 12, pp ,

45 O-BMI03 More than a picture: Biomedical Illustration Cenk Çelik *, Ozan Karaman, Aylin Şendemir Ürkmez 1 Ege University Bioengineering Department, Bornova, Turkey Keywords: Biomedical illustration, bone tissue engineering, hydrogel Introduction: A medical illustrator is a professional artist with advanced education in both life sciences and visual communication. Collaborating with scientists, physicians, and other specialists, medical illustrators transform complex information into visual images that have the potential to communicate to broad audiences. The work of medical illustrators promotes education, research, patient care, public relations, and marketing efforts. The field is changing rapidly due to discoveries in both science and technology. From the human genome to the latest robotic surgical techniques, the need for accurate effective communication continues to expand. In the past, the majority of medical illustrators were employed at large medical centers where they worked closely with physicians to produce illustrations for publications such as medical textbooks and scientific journals, as well as instructional videos, films, presentations, and exhibits. Today, there is growing need for accredited graduate programs in the area, and increased number of medical illustrators for dissemination of scientific results and knowledge to broader audiences. Methods: In this work, a novel method to repair large bone defects is being illustrated. Photoshop CS6 software and Uc-Logic Lapazz A5 graphic tablet were both used for biomedical illustration. Fig. 1. An illustration of a man pushing up. ( 2013 Dr Levent Efe, CMI Discussion & Conclusions: Medical illustration is a small field with less than an estimated 2,000 trained practitioners in the world. Yet, medical illustration is also a diverse field, and most professionals are obliged to develop specialties. Some specialize by subject area, such as surgery, veterinary medicine, or ophthalmology. Others specialize by which media they use, such as computer animation or the production of threedimensional models. Medical illustrators develop considerable knowledge and expertise within their specialty and become an integral part of the production team. Acknowledgements: Thanks to Medical Illustrator Merve Evren for her helps. [1] Medical Illustration (2013). Retrieved September 24, 2013 from 29

46 O-BMI04 ECG signals based diagnosis using artificial neural networks Yusuf Efteli*,1, Erkan Zeki Engin 1, Ozkan Arslan 1, Mehmet Engin 1 1 Ege University Electrical & Electronics Engineering Department, Bornova Izmir Keywords: Artificial Neural Network, ECG beat classification, MIT/BIH database Introduction: The recognition of the ECG beats is a very important task in coronary intensive units, where the classification of ECG beats is an essential tool for diagnosis. Pattern recognition, which can be divided into a sequence of stages, have provided to classify the ECG beats of different pathological classes. Firstly, extracted features can be considered as a condensed representation of the patterns. In the next step, the feature selection, smaller number of meaningful features, that the best represents the given pattern without redundancy, is defined. Finally, the classification is carried out, i.e., specific pattern is assigned to a specific class according to the characteristic features selected for it [1]. Methods: In this study, four different types of ECG classes: normal beats (N), paced beats (P), right bundle branch block (RBBB), and left bundle branch block (LBBB) beats were taken from Physiobank, MIT/BIH Arrhytmia database [2]. Third-order cumulant, wavelet based Shannon entropy, and auto-regressive coefficients were extracted for all ECG beats. The statistical test results confirmed that all features were significantly different in all signal classes [3]. We studied three types of ANN (Artificial Neural Network) training algorithms for ECG recognition: Levenberg- Marquardt (LM), Scaled Conjugate Gradient (SCG) and Conjugate Gradient Backpropagation (CGF) with Fletcher-Reeves. The ANN classifiers have one hidden layer with 15 inputs (coming from 5 cumulants, 6 entropy, 4 auto-regressive features) and one output layer with two neurons. The logarithmic sigmoid two neurons. The logarithmic sigmoid function was selected as the activation function. We used k-fold crossvalidation technique for reducing independency of performance to input data set. Results: The performances of the LM, SCG, CGF algorithms were: %97.6±2.81, %94±2.9, %93.64±2.47 for N beats, %97.16±1.86, %94.24±1.95 and % 93.52±2.81 for P beats, %94.48±2.58, %79.76±8.36 and %78.68±5.07 for RBBB beats, and %96.44±1.99, %83.4±2.4 and %81.92±6.07 for LBBB beats, respectively. Discussion & Conclusions: In this study, a novel ECG feature based ANN classifier system was proposed. The recognition results of the Levenberg- Marquardt training algorithm were better than those of the other classifiers and similar performances have obtained with the literature. The classification accuracy for LM training algorithm was %96.42±4.86. However, the most part of classification error has occurred for separating pathological classes. [1] N. Maglaveras, T. Stamkapoulos, K. Diamantaras, C. Pappas, M. Strintzis (1998), Int. J. Med. Inform., Vol.52, pp [2] Physiobank, MIT-BIH Arrhythmia Database, <> [3] M. Engin, M. Fedakar, E.Z. Engin, M. Korürek, (2007), Measurement, Vol. 40, pp

47 O-BMI05 The Investigation Of Diffuse Optical Tomography Simulations For Breast Cancer Monitoring İbrahim Akkaya *,1, Mehmet Engin 1, Erkan Zeki Engin 1, Mahmut Ozan Gokkan 1 1 Ege University Electrical & Electronics Engineering, Izmir, Turkey Keywords: breast cancer, Diffuse Optical Tomography, simulation Introduction: Near infrared tomography, also known Diffuse Optical Tomography (DOT), has been very popular and fast growing novel modality in a wide range of biomedical imaging such as oncology, neurology, dermatology etc. for two decades [1,2]. Its advantages are non-invasive, nonionizing, relatively cheaper, and safer application. DOT generally uses narrow near infrared (NIR) light band ( nm) to illuminate a tissue surface for collecting diffusely transmitted/reflected light and using some reconstruction algorithms for mapping the optical properties of tissue [1-3]. Herewith DOT can monitor tumors, hemoglobin concentration, and oxygen saturation levels, so it helps diagnosing and characterization of tissue. Methods: In this study, breast-like phantom element which represents physiological conditions of breast cancer tissue is used to monitor tumor by DOT technique. For this purpose a modeling and image reconstruction free software package (NIRFAST) was used [3,4]. The modeling and reconstruction theories which forward and inverse models algorithms are presented in this paper. The finite element method (FEM) which is the most commonly used approach has been used for the forward model of the system, optical properties of the system have been assigned from real data values, and the least square (LS) based methods has been used for the inverse solution [1-3]. Results: A few simulation examples like standard (single wavelength) and spectral (multi-wavelength) analyses have done. From the analysis results, absorption and scattering coefficients, chromophore distributions such as oxy-hemoglobin, deoxyhemoglobin and water levels have been presented and demonstrated. The results show that the used algorithms for DOT are fine to locate breast lesion. Also, we can separate the amount of absorption chromophores. Figure 1. Anomaly structure (tumor) detection of DOT Discussion & Conclusions: Consequently, the performance of DOT which is nonlinear and illposed problem has investigated and mentioned about its advantages, strong and weak sides with visual simulations. It shows that the diffuse optics is a promising tool in breast cancer diagnosis. [1] Guan Xu, (2006), Hebei University of Technology PhD Thesis, Enhancement of Near-infrared Diffuse Optical Tomography for Prostate Cancer Imaging. [2] Feng H., Jing B., Xiaolei S., Gang H., Junjie Y., A (2007), International Journal of Biomedical Imaging, Vol [3] Denghani H., Eames M.E., Yalavarty P.K., Davis S.C., Srinisavan S., Carpenter C.M., Pogue B.W., Paulsen K.D., (2007), J.Comp Phy. [4] Yalavarty P.K., (2007), Thayer School of Engineering Dartmouth College PhD Thesis, A Generalized Least Squares Minimization Method for Near Infrared Diffuse Optical Tomography. 31

48 Cell Number (x10 3 ) O-RM03 Effects Of The Architecture Of A Nerve Guide For Use In The Treatment Of Spinal Cord Injury T. Dursun 1,2, D. Yücel 1,5, Vasıf Hasırcı 1,2,3,4 1 BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, Ankara, Turkey METU, BIOMAT, Departments of 2 Biotechnology, 3 Biomedical Engineering,and 4 Biological Sciences, Ankara, Turkey Keywords: Nano/Micro Fiber, Nerve Tissue Engineering, Rat Bone Marrow Stromal Cell Introduction: Age, diseases or trauma cause damages to the nervous system which even may end up in inhibition of signal transfer [1]. "Nerve guides" are used to bridge neural gaps in the treatment of spinal cord injury. The architecture of the nerve guides is very important in performing its function at the injured site because the severed axons need to be reconnected during the healing process. Methods: The nerve guide consisted of a fiber layer on a foam structure. The bottom layer of the nerve guide, a PHBV foam, was prepared by lyophilization. Aligned and randomly oriented PHBV/collagen (2:1) fiber mats, to be placed over the base were made by electrospinning directly on the PHBV foam. Crosslinking was made by dehydrothermal treatment at 150 ºC for 24 h. After crosslinking, in situ biodegradation test was made in 10 mm PBS ph 7.4 at 37 ºC to study the degradation profile of these scaffolds. AF-Fo and RF-Fo nerve guides were seeded with rat bone marrow stromal cells (rbmscs) and incubated for 7 days. Cell behavior and differentiation to neural cells on these constructs was examined. Results: Mercury porosimetry showed that porosity of the PHBV foam was 85%, and the pore sizes were in between 5 and 200 nm. Diameter of the electrospun fibers are measured by SEM and found to in the range nm. In situ biodegradation test revealed that there was minimal weight loss of uncrosslinked guides, and therefore, crosslinking was abandoned. Cell attachment and proliferation were found to be better on the RF-Fo construct (Figure 1). The neural differentiation level of the cells was analyzed with flow cytometry and found to be the same on both constructs. After examination of cells with SEM, and fluorescence microscopy, evidence for the positive contribution of an aligned interior was observed Time of Culture (days) AF-Fo RF-Fo Fig. 1. Rat bone marrow stromal cell (rbmsc) proliferation on AF-Fo, and RF-Fo scaffolds. Cell seeding was 3x10 4 in neuronal differentiation medium. Discussion & Conclusions: It was concluded that the nerve guides prepared had proper porosity, pore size and degradation rate which would allow cell growth at the spinal cord injury site. Acknowledgements: We gratefully acknowledge the support by METU through the project BAP and The Scientific and Technological Research Council of Turkey (TÜBİTAK) for the 2205 BIDEP-TÜBİTAK Fellowship. [1] Schmidt CE., Leach JB. (2003). Annu. Rev. Biomed. Eng. 5: Author(s). (Year). Journal (Italic) Volume:Pages. 32 [2] Times New Roman, 10pt, Single spaced

49 O-RM04 Effects Of Low Intensity Vibratory Signals On Ultrastructure Of Mesenchymal Stem Cells During Adipogenic Commitment Öznur Başkan 1, Engin Özçivici *,1,2 1 Program in Biotechnology and Bioengineering, Izmir Institute of Technology, Urla, İzmir, Turkey 2 Department of Mechanical Engineering, Izmir Institute of Technology, Urla, İzmir, Turkey Keywords: cell ultrastructure, mechanical loads, mesenchymal stem cells, obesity Introduction: Prevalence of obesity have increased across the years in association with major decreases in human habitual activity, as technological developments supported nutritional availability and sedentary lifestyles. Increased physical activity is an available solution to prevent health concerns related to obesity, but lack of compliance for physical activity limits the integration of those benefits to the majority of the population [1,2]. An alternative to physical exercise, in which mechanical loads are naturally generated with a high magnitude and low frequency fashion, low magnitude and high frequency mechanical stimulation is also known to affect organisms positively [3]. In this study, we tested whether those low intensity vibratory signals (LIV) affect the ultrastructure of mesenchymal stem cells in vitro, when those stem cells are induced to commit adipogenic lineage. Methods: We cultured D1 ORL UVA mouse bone marrow mesenchymal stem cells with adipogenic induction (10% FBS, 1% P/S, 10nM dexamethasone, 5μg/ml insulin and 50μM indomethacine) for 7 days during which one group received daily LIV signals (90Hz, 0.1g) while the other served as a sham control. Phalloidin stains that visualize actin cytoskeleton of cells was utilized with DAPI stains of the cell nuclei followed by image analysis done by Image J software. Results: Vibrated cells had 73% (p<0.01) more fluorescent intensity compared to controls. Also the thickness of actin fibers in vibration group were 68% larger than control cells. There was a suggestive 75% (p=0.06) decrease in cell height in vibration group compared to control, as measured using atomic force microscopy. Discussion & Conclusions: We observed indications of ultrastructural changes in stem cells that are committed to adipogenic lineage by superposition of daily low intensity vibrations. If these mechanical signals are fit to prevent stem cells from committing adiposity by the changes in ultrastructure, this mode of exercise regimen can be used across the population with higher compliance. Acknowledgements: Financial support by The Scientific and Technological Research Council of Turkey (111T577) is gratefully acknowledged. [1] Gonzales-Gross M., Melendez A. (2013). Nutr Hosp 28: [2] Dwyer-Lindgren L., Freedman G., Engell R., Fleming T., Lim S., Murray C., Mokdad A. (2013). Population Health Metrics 11:7. [3] Rubin C. T., Capilla E., Luu Y. K., Busa B., Crawford H., Nolan D. J., Mİttal V., Rosen C. J., Pessin J. E., Judex S. (2007) National Academy of Science 104:

50 O-TM03 Chemical changes in plasma-treated NAC solution, leading to antimicrobial effect Utku Kursat Ercan*,1,2, Josh Smith 3, Frank Ji 3, Ari D. Brooks 2, Suresh G. Joshi 2 1 School of Biomedical Engineering, Science & Health Systems, Drexel University, Philadelphia, PA, Department of Surgery, Surgical Infections Research Program, Drexel University College of Medicine, Philadelphia, PA, College of Arts and Science, Department of Chemistry, Drexel University, Philadelphia, PA, Keywords: Infection Control, Non-Thermal Plasma, Plasma Chemistry, Plasma Medicine Introduction: Plasma is the fourth state of the matter and consist of ionized gas, charged particles, excited atoms and molecules, free radicals, and free electrons. Plasma has unique chemical characteristics, which are not still fully understood. Plasma medicine has been an emerging field especially for last couple decades, which combines plasma chemistry, plasma physics, and life sciences for therapeutic purposes [1]. Particularly, plasma disinfection is one of the most widely investigated areas of plasma medicine. Antimicrobial effects of non-thermal plasma is well known and widely reported [2]. Methods: In this study we have defined fluidmediated plasma treatment that combines direct and indirect plasma treatment methods. Previously we introduced 3-minute plasma-treated NAC solution as a novel antimicrobial substance with its broadspectrum effect on both planktonic and biofilm forms of microorganisms including multidrug resistant bacteria (such as MRSA USA300, K. pneumonia NDM-1)[3]. In the present study, chemical modifications that are caused on NAC molecule during non-thermal plasma treatment, and their contribution to antimicrobial effect are presented. Results: Our findings have shown that, following plasma treatment, ph of NAC solution drops to ~3, which is a characteristic consequence of plasma treatment of liquids. However low ph cannot be attributed any antimicrobial activity. Also we have quantified, nitrate, nitrite and hydrogen peroxide concentrations in the plasma treated NAC solution. Our further investigation has shown that, nonthermal plasma treatment causes chemical modifications on NAC molecule that causes formation of cysteic acid acetic acid. However any of above-mentioned species haven t showed any significant antimicrobial activity by themselves and in combination with each other. Using UV-vis spectrum, we have shown that first S- NAC (S-nitroso N-acetyl cysteine) is produced. In the presence of hydrogen peroxide S-NAC releases NO, which reacts with superoxide that is generated by plasma discharge, to form peroxynitrite, which seems to be the dominant species that leads to antimicrobial effect. Our accelerated aging and stability experiments have shown that plasma treated-nac solution can retain its antimicrobial acidity for an extended period of time. Discussion & Conclusions: We have demonstrated cellular responses such as intracellular nitrosative and oxidative stress, lipid peroxidation, cell membrane damage and differential gene expression that suggest peroxynitrite is the major species for antimicrobial effect. [1] Gregory Fridman, Gary Friedman, Alexander Gutsol, Anatoly B. Shekhter, Victor N. Vasilets, Alexander Fridamn (2008). Plasma Processes and Polymers. 5: [2] Suresh G. Joshi, Moogega Cooper, Adam Yost, Michelle Paff, Utku K. Ercan, Gregory Fridman, Gary Friedman, Alexander Fridman, Ari D. Brooks. (2011). Antimicrobial Agents and Chemotherapy. 55: [3] Utku K. Ercan, Hong Wang, Haifeng Ji, Gregory Fridman, Ari D. Brooks, Suresh G. Joshi, (2013). Plasma Processes and Polymers. 10:

51 O-TM04 New RBC trauma model applying a semi-empirical hemolysis approach Ali Poorkhalil*,1,2, Ghassem Amoabediny 2, Ali Kashefi-Khorasani 1, Khosrow Mottaghy 1 1 Institute of Physiology, RWTH Aachen University 2 Research Center for New Technologies in Life Science Eng., University of Tehran Keywords : artificial organs, RBC hemolysis, Semi- empirical model, Shear stress Introduction: Prediction of red blood cells (RBC) damage caused by different types of mechanical stress, in blood contact devices e.g. artificial organs, remains an important issue for modeling and designing. The current approaches used in modelling shear-induced blood damage can be classified in two main categories: Continuous models and Threshold models. Both of these approaches are based on empirical correlations which do not take into account entirely all the physical phenomena involved in blood damage. To overcome the limitations of current models, an alternative modeling approach, based on a physical description of the problem, was proposed by Vitale et al., although this model shows a fair agreement with the reported experimental data, improvements seem to be still necessary. Here we introduce a new semi -empirical approach based on our own experimental data and also including the already reported data. Methods: Recently two semi-empirical models using the literature data were reported by taking into account two physical phenomena. In the first model, hemoglobin release is described as a permeation process across the membrane, assuming as a shear stress dependent process (permeation model). In the second model, hemoglobin release is assumed to be caused only by membrane breakdown, which is established when RBC undergo for a time period longer than a threshold value (Nonuniform threshold model); The results of the analysis of these two model types confirmed the potential applicability of above mentioned modeling approaches for the course of blood damage. However, we consider the simultaneous effect of these two physical phenomena and it is realized by a combined model in which hemolysis is shear induced by considering a diffusion of hemoglobin across the membrane as well as a membrane breakdown. For validating the experimental data, we developed an high shear couette device. Results and discussions: For combination of these two models, we define here a weighted average damage index of both permeation and non-uniform threshold models. In this definition, the proportion coefficient will take a physical relevance in regard to the proportion of each phenomenon. The model is defined generally as: DI = a* II + (1-a)* I, Where: a: proportion coefficient (correspond to proportion of each phenomenon), I represents damage index predicted by permeation model and II equals to damage index predicted by non-uniform threshold model. In contrast to the previous models, the new model introduced here, by considering the dominated phenomena in each range of shear stress, represents a quite better agreement to the experimental data. Conclusions: The results demonstrate that here presented semi-empirical model predicts a high fitting behavior toward the experimental data in comparison to those already reported in the literature. [1] K. Mottaghy. (2000). Current Perspective of the Extracorporeal Circulation. [2] Flavia Vitale, (2011). Transacion in Chemical Eng. 35

52 O-TM05 Antiproliferative and antifungal activities of toad skin secretion (Bufo asper) Saad Sabbar Dahham *,1, Amin Malik Shah Abdul Majid 2 Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia; Minden 11800, Penang, Malaysia Keywords: Antifungal, Antiproliferative, Bufo asper Introduction: Amphibian skin secretions are a treasure store of bioactive peptides and proteins that are not only play as effectors in innate immunity, but also as modulators for adaptive immune system and possess potent therapeutic activities against microbial infection, diabetes, and cancer [1, 2]. Methods: skin secretions of Bufo asper were extracted via surface electrical stimulation (SES) [3].Protein concentration determination was carried out using Bradford method. The protein extract were characterized by SDS-PAGE and their anti proliferative activity was tested by studying the in vitro activities of (MCF-7, PC3, HCT116 and HUVEC) cell line and the results were assessed by MTT assay. Anti fungal activity were examined against Aspergillus niger, Penicillium citrinum and Trichoderma reesei using potato Dextrose agar plate by disc diffusion method. The anti fungal activity was evaluated by determined of inhibitory zone (DIZ). Results: The molecular masses of the proteins were in the range of kda as determined by SDS-PAGE. Concentration of protein in the sample solution was μg/ml. Seven concentration from skin secretions sample were evaluated for anti preoperative activity at ( μg/ml) on three type of cancer cell lines, breast MCF7, prostatic PC3, colon HCT116 and one normal cell line human umbilical vein endothelial cells HUVEC. The most sensitive cell were HUVEC with IC50 value (34.7 μg/ml), and the most resistant cell were colon cancer cell with( IC μg/ml), the IC50 value for Brest cancer cell was (159 μg/ml) and for prostatic cancer cell was (138 μg/ml) respectively. on the other hand, high antifungal activity was recorded on A. niger DIZ value was 23mm, followed by P. citrinum with 20mm. the least activity was recorded on T. reesei DIZ value was 15mm. These finding reveals that the antimicrobial peptides (AMPs) has broad biological activity spectrum such as ant microbes and anti tumors. Conclusions: There is a great interest on the secretions from amphibian skin to discover new pharmacological agents, especially useful for drugbased cancer treatments. Further investigations are needed to identify the compounds from toad and frog skin secretion associated with the antiproliferative and antimicrobial properties. [1] Conlon, J.M., Leprince, J. (2010). Peptidomics, methods in molecular biology 615, [2]Bevins, L.C., and Zasloff, M. (1990) Annu. Rev. Biochem. 59: [3]. Maselli VM (2006) Amphibian neuropeptides. Isolation, sequence determination and bioactivity. Thesis, the Univ., of Adelaede Australia 36

53 Heat Values O-TM06 The Heat Calculation Based Monte Carlo Modelling For Monitoring Of Tissue Physiological Conditions In Semi- Infinite Scattering Medium M. Ozan Gökkan*,1, İbrahim Akkaya 1, Mehmet Engin 1, Erkan Zeki Engin 1 1 Ege University, Electrical & Electronics Engineering, Izmir, Turkey Keywords : Biological tissue, Heat, Monte Carlo simulation, Optical properties Introduction: The development of Monte Carlo (MC) simulation is closely related to the first computer codes for neutron physics developed during the Manhattan project for producing the atomic bomb during the 1940s [1]. Because of the fact that the MC method aims to facilitate the complex mathematical models with iterative approach, in this application, MC modeling of light transport in multi-layered tissues were used to simulate the human skin depending on the absorption and scattering coefficients to obtain a heat produced in homogeneous and semi-infinite scattering medium [2]. The heat in a turbid medium with optical properties is typically the vibration of atoms that are the basis of the particles and molecules in a medium. When photons hit an atom's electrons, the electrons of that atom can shift positions due to vibrations. Hence, the heat is produced. Methods: The aim of this study is to calculate the heat during photon transport in which the model consists of 101 plane-parallel slab of finite thickness, is 20 μm for each bin, so the model handle the diffuse (or backscattered) during photon travelling and Fresnel reflectance. All media were assumed to be forward scattering with indices of refraction between 1.00 (air) and 1.5 (all medium) and albedo is In addition, creating a photon packet with a specific weight was initialized as a unity for this application is more practical than propagating photons individually. As the photon interacts in the scattering medium, it will deposit weight due to absorption and the remaining weight will be scattered to other parts of the medium until it is terminated, reflected, or transmitted [2, 3, 4]. Results: Entire process was repeated for photons due to Monte Carlo technique. Thereby, as illustrated in Fig. 1, the heat values corresponding to the depth of the biological tissue for each layer were calculated and seen that it decreased when photons being penetrated deeper Depth (µm) Heat values Fig. 1. Simulated heat values corresponding to the depth of a skin. Conclusions: The model we have may be a useful approach for early diagnosis of skin cancer by monitoring heat values. This is because the released heat in a cancerous tissue, which is a strong absorber, becomes quantitatively more than normal tissue, when a photon encounters with a tumor in the skin. [1] Stochastikon Encyclopedia, (http:// :8080/encyclopedia/en/montecarlo.pdf), Monte Carlo Simulation. [2] S.A. Prahl, 1988, Light Transport in Tissue (PhD). [3] W. Lihong, S.L. Jacques, 1992, Monte Carlo Modeling of Light Transport in Multi-layered Tissues in Standard C (PhD Thesis). [4] S. A. Prahl, M. Keijzer, S. L. Jacques, A. J. Welch, 1989, A Monte Carlo Model of Light Propagation in Tissue, Vol. 5, pp

54 O-AO03 Design, construction and feedback control of an elastance-driven mock circuit Emir Gökberk Eken*, 1, M. Erol Sezer 1, Kamuran A. Kadıpaşaoğlu 1 1 Bahçeşehir University, Istanbul Turkey Keywords: Cardiovascular, Elastance, Feedback Control, Mock Circuit Introduction: Active systolic elastance of the ventricles and the passive diastolic elastance of the large arteries (aorta and pulmonary artery) are not easily integrated in cardiovascular mock circuits (MC), partially due to the fact that both parameters vary during the cardiac cycle. While ventricular elastance is time-dependent, arterial elastance is volume-dependent. Methods: We constructed a feedback control algorithm in Simulink, which we implemented (dspace) to drive a 4-chamber physical MC formed of closed reservoirs (area A) and filled with pressurized air above a water column (height h).[1] Pneumatic valves α and β implemented (dspace) a theoretically formulated time-varying activation function [2], which generated the LV elastance (1/compliance) which, in turn, controlled the LV pressure. The initial pressurizing factor of the aortic reservoir, γ, was adjusted to keep the aortic compliance constant across the operating range of reservoir volumes and pressures. The aortic resistance and aortic outflow were used as control and feedback variables, respectively, in the proportional control algorithm. Fig. 1. Left Ventricle Pneumatic System Design Results: Ventricular and arterial pressures were satisfactorily maintained within desired physiologic range during normal (resting, exercise) and pathological (systolic/diastolic LV failure) physiologies. Fig. 2. Left Ventricle and Aorta Pressures (left), P-V Loop Discussion & Conclusions: PV loops of the normal physiology are re-created with acceptable accuracy. The system will be expanded in order to incorporate the pulmonary side of the mock loop, as well. The MC is intended for testing the performance of new prototypes and operational control for a novel axialflow LVAD [3], currently under development in our laboratories. Acknowledgements: This work was supported by Grant No 111M243 from TUBİTAK (1001) and Grant No STZ by the Ministry of Science, Industry and Technology (San-Tez). [1]EG.Eken, S.Seker, E.M.Sezer, K.A.Kadipasaoglu, (2012), ASAIO Journal Vol. 58, 32 pp., [2]E.M.Sezer et al., (2012) ASAIO Journal Vol. 58, 44 pp., [3]K.Toptop, K.A.Kadipasaoglu, (2013) ASAIO Journal, pp. 38

55 O-AO04 A new oxygenation and integrated pump system for extra-corporeal application Ali Kashefi *,1, Ali Poorkhalil 1, K. Mottaghy 1 1 Institute of Physiology, RWTH Aachen University Keywords : Artificial organs, ECMO, Hollow fiber, Oxygenator, Pump Introduction: A hollow fiber membrane contactor mainly comprises a module and hollow fiber bundles. Generally, in gas-liquid contactors, gas flow is passed through the fibers and liquid flows outside. Mass transfer occurs as the result of partial pressure drop of a common particle between gas and liquid phases. Normally in the heart surgery and Exrtacorporeal Membrane Oxygenation ECMO, a pump e.g. roller pump is used to circulate the blood and the system usually has a big priming volume. It is crucial to minimize the priming volume either by reducing the oxygenator priming volume or shortening the circuit. We introduce here a new design self pumping oxygenator for extra-corporeal circuits in which oxygenation and pumping are integrated and priming volume is minimized. The additional advantage is that the system can vary the stroke volume and frequency in analogy to physiological natural cardiac output. Results and discussions: Pumping system can provide the flow rate up to 700 ml/min with frequency of 108 per min. The gas analysis results showed the high gas transfer performance of the oxygenator. In this flow rate, oxygenator can exchange 43.8 and 39.4 ml/min, oxygen and carbon dioxide respectively which are higher than commercial oxygenators, if we consider its surface area. Conclusions: The oxygenator, as a prototype, showed promising results, which indicate that it will be worthwhile to dedicate future research to its improvement. [1] K. Mottaghy. (2000). Current Perspective of the Extracorporeal Circulation. [2] Stefan Silbernagl, Agamemnon Despopoulos, Color Atlas of Physiology, 6th edition [3] Tabesh, H., et al., (2012) J Artif Organs 15: [4] AAMI Standard (ISO 7199), 2009 Methods: The system has three main features: 1) Oxygenation and pumping the blood simultaneously by means of sucking and pumping the blood with a new designed elastic oxygenator hosing and two passive valves 2) Elimination of roller pump which gives this possibility to have very small circuits with as low as possible priming volume 3) Pulsatile pumping leads to generation of secondary flow in oxygenator which gives a higher efficiency of gas exchange. 39

56 O-AO05 Blood flow analysis through right ventricle-pulmonary artery conduit stenosis by computational fluid dynamics K.B. Kose 1, N. Arslan*,2 E. Ödemiş 3, H.T. Tola 3 1 Fatih University,) Genetic and Bioengineering Department, Biofluid Mechanics Laboratory 2 Fatih University,) Mechanical Engineering Department, Biofluid Mechanics Laboratory 3 İstanbul Mehmet Akif Ersoy Chest & Cardiovascular Surgery Training & Research Hospital, Pediatric Cardiology Department Keywords: CFD, Conduit, CT, Pulmonary Artery, Turbulent Flow Advances in mathematical methods and three dimensional (3D) patient specific imaging techniques play important role for understanding the blood flow [1] and its physiological, mechanical and pathological effects. Introduction: The aim of this study is to understand the blood flow behaviour through the conduit and detecting the critical flow regions by computational fluid dynamics (CFD) methods. Methods: 3D computed tomography (CT) images obtained from the patient who has conduit implantation (Figure 1). The realistic geometry is reconstructed by image segmentation, computer aided design an image processing methods (Figure 2). The volume is meshed by grid generation and blood flow re-generated by CFD [2]. Results: In turbulent flow, the maximum velocity is 40 m/s. However it was 32 m/s and the streamlines were significant for laminar flow. The jet-like flow was seen through the conduit and seperation regions detected after the neck. In turbulent and laminar solving the low shear stress regions which can effect the endothelial cells are detected. Reynold Stress is calculated as dyne/cm 2 (Figure 3). Fig. 3. Reynolds Stress distribution in turbulent Flow Discussion & Conclusions: The results designate the effect of the geometry which can cause the critical risks for the patient and patient-specific information and gives direction to surgeons, to advance the most effective treatments to the patients. Acknowledgements: We thank to Assoc. Prof. Dr. İhsan Bakır who is the CEO of Istanbul Bakirkoy Public Hospitals and the radiologists and technicians of İstanbul Mehmet Akif Ersoy Chest & Cardiovascular Surgery Training & Research Hospital for their valuable help to this study. : [1] Arslan, N. (2006) Mathematical and Computational Applications, Vol. 11, No. 3, pp [2] Thiriet M. (2008) Biology and Mechanics of Blood Flow. Springer. [3] Timothy W. Secomb, T. W.,Barber O.J. and Restepo J.M. (2009) Computatinal Simulation of Red Blood Cell Motion in Microvesel Bifurcations. CSIRO. 40

57 O-AO06 Modeling And Simulation Of Blood Oxygenation In A Hollow-Fiber Membrane Oxygenator (Hfmo) Ali Rasouli. 1, G. Amoabediny, *,1, H. Tabesh, 2, M. Moaddab 1, Nabi Asmani, M. 1, Ali Kashefi 2, K. Mottaghy 2 1 Dept. Of Chemical Eng., Faculty Of Eng., and Dep. of Biomedical Eng., Research Center for New Technologies in Life Science Eng.,University Of Tehran, Tehran, Iran 2 Institute of Physiology, RWTH Aachen, Aachen, Germany Keywords: Design optimization, HFMO, Oxygenation, Semi-empirical model Introduction: Oxygen dissolves physically in blood plasma and also bonds chemically to the hemoglobin of erythrocytes [1]. However, the latter has a dominant role in blood oxygenation [1]. An artificial lung, also known as oxygenator, should be able to oxygenate the blood near to the physiological values. Modeling and simulation of blood oxygenation is kind of challenging. While the blood parameters have contradictory effect on each other, the prediction of blood oxygenation is of crucial importance especially in medical devices such as oxygenators. Methods: An appropriate semi-empirical model to calculate the oxygen transfer coefficient in blood was developed including gas transfer resistances and also the Sherwood number [2]. As a novelty of this work, COMSOL Multiphysics 4.2 has been used as a computational fluid dynamics (CFD) commercial simulator to model the blood and gas transfer. A set of three different cylindrical HFMO prototypes with defined specifications, comparable to current commercialized adult oxygenators, were designed and fabricated. These HFMOs represent similar priming volumes and membrane surface areas while differ in module length. The design specifications of the prototypes were further sketched and meshed by the simulator. Then, the proposed model including the gas transfer coefficient was implemented into the simulator to predict the oxygen transfer from gas phase to liquid one. Moreover, in order to measure the oxygen transfer rate, the oxygenators prototypes were experimentally investigated in-vitro, due to AAMI standard [3], using the fresh and heparinized porcine blood. Results: Simulation results demonstrate a high degree of agreement with those of in-vitro investigations. This fact validates the proposed model and corroborates the possibility of application of computational simulations in predicting the performance characteristics of HFMOs. Comparing the simulation and in-vitro experiment results of the three prototypes reveal that the shorter module length, the lower pressure drop. In addition longer module length would result in a higher gas transfer rate. Discussion & Conclusions: Prediction of blood oxygenation with computational simulation software is an alternative method in order to calculate the blood oxygen uptake in HFMOs. This approach can substitute the sophisticated in-vitro investigations using natural animal/human blood. Furthermore, simulation of blood oxygenation could be an important applicable tool in order to optimize the design of oxygenators and subsequently efficient performance characteristics. Considering the results of the three prototypes, the one with lower module length would be more desirable since it presents an adequate oxygen transfer rate and a lower blood pressure drop at the same time. [1] Stefan Silbernagl, Agamemnon Despopoulos, Color Atlas of Physiology, 6th edition [2] Tabesh, H., et al., 2012, J Artif Organs 15: [3] AAMI Standard (ISO 7199),

58 O-TM08 Daily mechanical vibrations reduce number of aggressive type breast cancer cells by interfering with their cell cycle Melis Olçum 1, Engin Özçivici*,2 1 Izmir Institute of Technology, Bioengineering Graduate Program Izmir,Turkey 2 Izmir Institute of Technology, Mechanical Engineering Department Izmir, Turkey Keywords: breast cancer, cell cycle, mechanical vibration Introduction: Across the female population breast cancer is the highest reason of cancer related fatality worldwide [1]. As treatment strategies for cancer such as chemotherapy and radiotherapy has uncertain efficiency and are associated with excruciating physical and physiological pain, strategies against cancer relies on preventive measures [2]. Physical activity, is accepted to be one of the most important prevention against several types of cancer, including breast cancer as well [3, 4]. Although it is clear that physical activity has systemic effects on immune and metabolic process, it is not clear how physical forces affect cancer cells directly [5]. Cancer cells were shown to alter their microenvironment to soften their cell structure and harden their extracellular matrix, while forming the tumor tissue [3, 6, 7]. Since healthy cells rely on mechanical forces in their normal physiological processes, how alterations in mechanical load sharing in tumor tissue affect cancer cells is not known. Methods: External physical stimulation was a vibrational sine wave, with a magnitude of 0.1 g and a frequency of 90 Hz that is applied for 15 min per day on aggressive type breast cancer cells (MDA- MB-231). Results: Number of cells significantly decreased in vibration group for 5, 7 and 10 days of application, 78%, 32% and 27% respectively (all p<0.05). Cell viability with MTT tests showed a decrease of 62%, 18% and 50% for 5, 7 and 15 days of application (all p<0.05). Cell cycle analysis with PI showed that mechanical forces kept cells in G1 phase on 7 and 10 days of application. Vibrated groups has 24% and 18% reduction in G2 phase cells respectively (all p<0.05). No significant effect was observed for vibrations in apoptosis of cancer cells, performed by Annexin V-PI stains. Similarly, vibrations did not affect the migration of breast cancer cells. Discussion & Conclusions: According to our results, daily applied mechanical forces affected cell growth and division on aggressive type breast cancer cells, potentiating a complementary option for medical struggle against breast cancer. Acknowledgements: Financial support by The Scientific and Technological Research Council of Turkey (111M604) is gratefully acknowledged. Expert technical help from Dr. Ozden Yalcin- Ozuysal, Esra Erdal and Izmir Institute of Technology, Biotechnology and Bioengineering Research and Application Center is appreciated. [1] Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, Baade PD. Cancer Epidemiol 2012, 36(3): [2] Seyfried TN. Cancer as a Metabolic Disease. 2012: [3] Friedenreich CM, Orenstein MR. J Nutr 2002, 132(11 Suppl):3456S-3464S. [4] Lee CD, Sui X, Hooker SP, Hebert JR, Blair SN. Ann Epidemiol 2011, 21(10): [5] King B, Jiang Y, Su X, Xu J, Xie L, Standard J, Wang W. Exp Biol Med 2013, 238(5): [6] Brabek J, Mierke CT, Rosel D, Vesely P, Fabry B. Cell Commun Signal 2010, 8:22. [7] Suresh S. Acta Biomater 2007, 3(4):

59 O-TM09 A new respiratory training system with a controlled CO2 elimination for high altitude training Ali Kashefi *,1, Ali Poorkhalil 1, Ali Khachab 1, Khosrow Mottaghy 1 1 Institute of Physiology, RWTH Aachen University Keywords: CO 2 Elimination, HAT, Hollow fiber, Oxygen, Respiratory Training Introduction: High altitude training (HAT) is often used by athletes to increase the number of red blood cells, which is believed to increase endurance performance. This training is a common practiced training regimen in sport science whether for enhancing the overall stamina or for accelerating postinjury recovery time. The merit of all available HAT systems focuses on the reduced oxygen delivery inspired by the practitioner. However, the respiratory CO2 is physiologically considered to be as vital as O2 in determining the appropriate inspiratory conditions. Another shortcoming is the lack of user control, which has to be considered as an essential aspect in delivering an individual effective regimen. Presented here is a total respiratory closed system integrating mainly a hollow fiber gas exchange device, including a ventilator (air pump). Methods: Characterization of the different hollow fiber modules during the gas-gas exchange employs a semi empirical procedure. The experimental stage includes two distinctive construction designs utilizing different membrane materials to be validated through computational analysis of the here for established mathematical equations. Results and discussions: The principle of integrating hollow fibers has proved to be a feasible approach for controlling HAT. In contrast to current available systems, the presented innovation has to major advantages: The variable dead space volume allows the control of po 2 and pco 2 courses in the inspiratory air gas composition. Also, the air ventilation rate of the hollow fiber device over the end point data can be controlled. Experimental results are in accordance to theoretical predictions. Conclusions: Controlled HAT based on hollow fiber materials can provide a high flexibility in modifying the individual input conditions of each case and thereby, it may be considered as a big step in improving the quality of high altitude training. [1] Stefan Silbernagl, Agamemnon Despopoulos, Color Atlas of Physiology, 6th edition [2] K. Mottaghy. (2000). Current Perspective of the Extracorporeal Circulation. [3] Tabesh, H., et al., 2012, J Artif Organs 15: [4] AAMI Standard (ISO 7199),

60 O-TM10 A Novel Approach To Measure CO2 Transfer Rate Through An Artificial Lung M. Moaddab 1, G. Amoabediny *,1, H. Tabesh 1,2, Ali Poorkhalil 2, Ali Rasouli 1,, Ali Kashefi 2, K. Mottaghy 2 1 Dep of Life Sciences Eng., Faculty of New Sciences and Technologies, and Dept. of Chemical Eng., Faculty of Eng., and Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, Iran 2 Institute of physiology, RWTH Aachen, Aachen, Germany Keywords: Artificial Lung, CO 2 Transfer Rate Introduction: Eliminating a part of blood's CO 2 content is one of important functions of the natural lung which has a great influence on blood's parameters e.g. ph [1]. Therefore, an oxygenator, as an artificial lung, should have the capability for an efficient CO 2 removal, along with the blood oxygenation, comparable to that of natural lung. Methods: As CO 2 dissolves in water, carbonic acid is produced which itself dissociates to HCO 3 - and CO These equilibrium reactions result in H + release, and subsequently, the reduction of the solution's ph. Having the ph value, the concentrations of hydroxide, carbonate ion, bicarbonate, carbonic acid, and carbon dioxide in addition to pco 2 and consequently the total CO 2 content are computable using the first and second acid dissociation contestants in addition to the hydration and CO 2 Henry s constants. A closed experimental circuit was designed pumping distilled and deionized water through the liquid phase of an oxygenator while pure CO 2 flows into its gas phase. A high-sensitive ph sensor (FPH- BTA Tris-Compatible, Vernier Inc., USA) was placed into the reservoir recording the ph fluctuations due to time. HILITE 2800 and HILITE 7000 hollow-fiber membrane oxygenators (Medos AG, Germany), as commercialized pediatric and adult oxygenators respectively, were investigated using a Stöckert SIII Heart Lung Machine (Stöckert Instrumente GmbH, Germany). Water flow rates were set 400, 1200, 2000, 2800 and 1000, 3000, 5000, 7000 (ml/min) for HILITE 2800 and 7000 oxygenators respectively while the ratio of CO 2 flow rate to that of liquid was adjusted 1:1 for every experiment. Results: The results show a sharp reduction of ph from 7 to around 4.3 as CO 2 was dissociated into water. The ph then became constant around 4.3, when CO 2 transfers between gas and liquid phases were in equilibrium (as shown in figure 1). Taking into account the initial and final ph, the total concentration of transferred CO 2 and the relative CTR is achievable concerning the ph-drop time. Comparing the calculated CTRs with those measured in-vitro using native porcine blood, at the same operating conditions, concerning the AAMI standard [2], shows a high degree of correspondence which, in turn, validates the proposed method. Fig.1: ph drop due to CO2 dissociation is water Discussion & Conclusions: This novel method provides the possibility for a rapid, inexpensive and, at the same time, accurate measurement of CTR in various oxygenators. Therefore, the conventional off-line natural blood investigations of oxygenators can be substitute using the proposed reliable alternative on-line method. In addition, the application of this method can be expanded for invitro gas exchange investigations in every type of gas-liquid membrane contactors. [1] Stefan Silbernagl, Agamemnon Despopoulos, Color Atlas of Physiology, 6th edition. [2] AAMI Standard ISO 7199,

61 O-RM07 Fabrication of osteon-mimetic microtubes for bone regeneration Ozan Karaman 1,2, Esmaiel Jabbari *,2 1 Department of Bioengineering, Ege University, Bornova, Izmir, Turkey 2 University of South Carolina, Columbia, SC, USA Keywords: Biomineralization, Microtubes, Nanofibers, Osteogenic differentiation Introduction: Each year, there are more than 2.2 million skeletal injuries that require bone graft procedures worldwide. The success of the engineered bone grafts mostly depends on how much it can mimic the micro- and nanoscale of bone tissue. The bone structure consists of microtubules like osteons that are formed by laminated layers of calcium-phosphate (CaP) deposited aligned nanofibers (NF). Therefore, we hypothesized that fabricating microtubes with CaP deposited aligned NF would mimic the lamella structure of osteons. To this end, the objective of this work was to evaluate the microtubuler scaffold on the extent of in vitro osteogenesis. Methods: CaP deposited aligned NF were fabricated by electrospinning and further incubation of NF in 10 times concentrated simulated body fluid (10xSBF) for 24h. Next, well-defined macropores formed on the CaP deposited NF microsheets with 34 GTV needle (0.18 mm outer diameter) in order to enhance diffusion of nutrients inside the microtubes. Next, approximately 25 µm thick CaP deposited NF based microsheets were wrapped tightly around stainless steel rods with different inner diameters, and the assembly was annealed 80 C for ten minutes to get uniform perforated microtubes. Microtubes with inside diameters of 0.25, 0.35, 0.45 and 0.8 mm were fabricated. A set of macroporous microtubes bonded to fabricate osteon-mimetic fibrous scaffolds. The 0.35 and 0.8 inner diameter microtubes were used for further cell culture experiments. First, microtubes were sterilized by ethanol and ultraviolet radiation. Next, microtubes conditioned with primary culture media for 1 h prior to cell seeding. CaP deposited NF microsheets were used as a control. MSCs were isolated and selected from the bone marrow of Wistar rats and seeded with 1 x 10 5 cells/cm 2 density and cultured in osteogenic media for up to 28 days for testing osteoconductivity of the substrate. The osteogenesis was determined by measuring DNA content, alkaline phosphatase (ALPase) activity, calcium (Ca) content, and total collagen content. Results: The uniform microtubes with macropores were successfully fabricated with different inner diameter upon annealing of the wrapped CaP nucleated microsheets. MSCs cultured in osteonmimetic 0.35 mm (*) and 0.8 mm (**) inner diameter microtubes had significantly higher ALPase activity, calcium content, total collagen content and expression of osteogenic markers, compared to microsheets. Discussion & Conclusions: The data demonstrates that the 3D microstructure of the microtubes enhances osteogenic differentiation of MSCs. However, the change on the size of the microtubes did not have significant effect on osteogenic differentiation of MSCs. Acknowledgements: This work was supported by grants from the National Science Foundation under Grant No. CBET and CBET [1] Karaman, O., Kumar, A., Moeinzadeh, S., He, X., Cui, T., Jabbari, E. (2013). Journal of tissue engineering and regenerative medicine. 45

62 O-RM08 In vivo somatic cell reprogramming towards pluripotency within the mouse tissue Açelya Yılmazer 1,2, Irene de Lázaro 2, Cyrill Bussy 2, Kostas Kostarelos *,2 1 Biology Department, Science Faculty, Ankara University, Tandoğan, Ankara, Turkey 2 Nanomedicine Lab, UCL School of Pharmacy, London, UK Keywords: hepatocytes, in vivo, ips cells, pluripotency, reprogramming Introduction: The ability to induce the reprogramming of somatic mammalian cells to a pluripotent state by the forced expression of specific transcription factors has opened possibilities for disease modeling, drug screening and regenerative medicine. Following the discovery by Yamanaka in 2006 [1], induced pluripotent stem (ips) cells have been generated by variety of methods and with different starting cell types. However, the vast majority of current methodologies to generate ips cells still show low reprogramming efficiencies (1%) and involve the use of long-term and complex culture conditions. Hypothesis: We hypothesized that the non-viral expression of the four originally discovered transcription factors Oct3/4, Klf-4, Sox-2 and c- Myc (OKSM) in adult mice could result in in vivo reprogramming of cells in the transfected tissue [2]. Results: We show that a single hydrodynamic tailvein (HTV) injection of plasmids encoding for the OKSM factors, can be delivered to the liver of Balb/C mice. With this method, a significant increase in the gene expression of all OKSM factors was observed in the mice liver after 8 hours. Main pluripotency markers were upregulated within 24-48h after injection, followed by down- regulation of all major hepatocellular markers. In vivo generation of reprogrammed cells was further supported by the positive staining of liver tissue sections and qrt- PCR analyses of all major pluripotency markers. Further confirmation of the generation of reprogrammed cells in the liver was offered by the presence of egfp-positive cells in Nanog-GFP mice liver following the HTV injection of OKSM factors. The reprogrammed liver samples which were examined up to 120 days, did not show any signs of physiological or anatomical abnormalities or teratoma formation. Discussion & Conclusions: These findings indicate that non-viral expression of OKSM factors in vivo can reprogram cells in situ rapidly, efficiently and transiently, in the absence of host tissue damage or teratoma formation. Furthermore, with improved protocols and technologies, it might be possible to extract in vivo induced pluripotent cells that can be used and analyzed for future studies. [1] Takahashi, K., Yamanaka, S. (2006). Cell 126: [2] Yilmazer, A, de Lazaro, I., Bussy, C., Kostarelos, K. (2013) PloS one 8:e

63 O-RM09 Chitosan/poly-L-lysine Composite Tubes in Sciatic Nerve Melis Olçum 1, Oğuz Gözen Damages 2, Lütfiye Kanıt 2, Ersin Oğuz Koylu 2, Aylin Şendemir Ürkmez*,2 1 Izmir Institute of Technology, Izmir, Turkey 2 Ege University, Center for Brain Research, Izmir, Turkey Keywords: Chitosan, Poly-L-lysine, Scaffold, Sciatic Nerve Injury Introduction: Peripheral nerve damages may occur because of many reasons in daily life, such as traffic and sport accidents, viral infections or systemic diseases [1]. Damages to peripheral nerves often result in functional loss and affect social and daily life of patients. Chitosan is a biodegredable and biocompatible natural polysaccharide derived from crustaceans. It has been studied in drug delivery systems, food packaging and tissue engineering. Chitosan has been shown to promote regeneration in peripheral nerves in vivo and in vitro [2-4]. Poly- L-lysine is another natural polymer that promotes cell adhesion and used frequently in cell culture studies for coating [5, 6]. Chitosan and poly-llysine composition has been studied in membrane forms and found to be supportive for cell differentiation and proliferation [7]. Methods: Tubular chitosan and chitosan/poly-llysine conduits were prepared as liquid mixtures, solidified by controlled freezing and lyophilized. Conduits were characterized by SEM imaging and mechanical testing. After generation of a 8 mm gap on rat sciatic nerve, it has been bridged by the porous conduits. Functional recovery was followed by walking analysis and grip tests for 20 weeks. At the end of the testing period, nerve regeneration was evaluated histologically with haematoxylin-eosin staining. Results: Composite tubes were found to have significantly higher Young s modulus than chitosan alone tubes (p<0.05). Also their percent elongation was significantly higher (p<0.05). No significant difference was observed in tensile strength between groups. Histological evaluation revealed that the composite group was more supportive for cell adhesion and nerve regeneration compared to chitosan-alone group. However, functional analyses did not sufficiently support these results. Discussion & Conclusions: The composite conduits were found to be supportive for peripheral nerve regeneration but functional data were insignificant. In order to increase functional significance, including other functional experiments are recommended. Acknowledgements: This work has been supported by Ege University Science and Technology Center (EBILTEM) Project no: 2010BAUM Jkema-Paassen, I., J., K. Jansen, A. Gramsbergen and M. F. Meek, 2004, "Transection of peripheral nerves, bridging strategies and effect evaluation." Biomaterials 25(9): Kim, I. Y., S. J. Seo, H. S. Moon, M. K. Yoo, I. Y. Park, B. C. Kim and C. S. Cho, 2008,. "Chitosan and its derivatives for tissue engineering applications." Biotechnol Adv 26(1): Muzzarelli, R. A. A., 2009, "Chitins and chitosans for the repair of wounded skin, nerve, cartilage and bone." Carbohydrate Polymers 76(2): Haipeng, G., Z. Yinghui, L. Jianchun, G. Yandao, Z. Nanming and Z. Xiufang, 2000, "Studies on nerve cell affinity of chitosanderived materials." J Biomed Mater Res 52(2): Boylan, N. J., A. J. Kim, J. S. Suk, P. Adstamongkonkul, B. W. Simons, S. K. Lai, M. J. Cooper and J. Hanes, 2011, "Enhancement of airway gene transfer by DNA nanoparticles using a ph-responsive block copolymer of polyethylene glycol and poly-l-lysine." Biomaterials. 6. Tiera, M. J., Q. Shi, F. M. Winnik and J. C. Fernandes, 2011, "Polycation- based gene therapy: current knowledge and new perspectives." Curr Gene Ther 11(4): Mingyu, C., G. Kai, L. Jiamou, G. Yandao, Z. Nanming and Z. Xiufang, 2004, "Surface modification and characterization of chitosan film blended with poly-l-lysine." J Biomater Appl 19(1): Yu, H., C. Deng, H. Tian, T. Lu, X. Chen and X. Jing, 2011, "Chemo-physical and biological evaluation of poly(l-lysine)- grafted chitosan copolymers used for highly efficient gene delivery." Macromol Biosci 11(3):

64 O-BM07 Characterization Of Micropatterned Collagen Films For Corneal Stroma Engineering Cemile Kılıç 1,2,4, Vasıf Hasırcı*,1,2,3,4 Departments of 1 Biological Sciences, 2 Biotechnology, 3 Biomedical Engineering, METU, Turkey 4 BIOMATEN- Center of Excellence in Biomaterials and Tissue Engineering, METU, Turkey Keywords: Collagen, Cornea, DHT, Micropattern, Tissue Engineering Introduction: Corneal stroma is about 400 μm in thickness and the lamellae forming this layer are parallel to the corneal surface and orthogonal to adjacent lamellae that form a plywoodlike structure. This organization is essential for the biomechanical and optical properties of the cornea and current study aims to mimic it by using micropatterned collagen films. Micropatterned collagen films were prepared to guide the stromal keratocytes to simulate the microstructure of the natural stromal fibrils to be used as corneal stroma equivalent. Methods: Collagen films were prepared by solvent casting on a micropatterned silicon wafer and crosslinked by dehydrothermal (DHT) treatment consisting of heating under vacuum for 24 h. The films were characterized by studying their in situ and enzymatic degradation profiles, and contact angles were measured. The cell numbers on the films were determined by Alamar Blue assay and the alignment of keratocytes was studied by DAPI- Phalloidin staining and SEM analysis. Transparency, a crucial property of a cornea substitute was measured in the UV-Vis range. Results and Discussions Collagen films were crosslinked by DHT treatment and different temperatures were used to find optimal crosslinking temperature which does not deteriorate the pattern of the films during tissue culturing. In order to preserve transparency and other vital functions of the cornea, the topography of the scaffold should not be disrupted by the enzymes until the cells secrete their own ECM. According to enzymatic and in situ degradation tests, 150 o C for 24 h (DHT150) was the best among others where the topography of the patterns were preserved after 2 h treatment with collagenase type II or 4 week incubation in PBS at ph 7.4. Moderately wettable surfaces support cell attachment and proliferation. Contact angles of the crosslinked collagen films were quite high due to the micropatterned nature of the films where unpatterned films displayed lower contact angl es (117 o vs 98 o ). However, the contact angles were significantly decreased by time while the drops repositioned on the patterns. Isolated human stromal keratocytes (p5-13) were seeded on the patterned collagen films. The cells could align even within a day of culture and the number of the cells increased 17 fold in 21 days. On the unpatterned films, however, the cells were randomly distributed. Transparency of the films was decreased upon increasing crosslinking temperature (85% vs 77%, uncrosslinked vs DHT150, at 700 nm); however it improved over a 30 day period when the films were seeded with keratocytes (77% vs 92%, Day 0 vs Day 30) at 700 nm which was quite close to that of the native cornea (99%). Transparency of the unseeded films in the same period did not improved and it was significantly lower than the seeded ones at each time point (73% at Day 30). Conclusions: DHT150 micropatterned films were shown to support cell attachment and proliferation and the transparency was quite high. The constructs appear to have the potential for use as a stroma equivalent. Acknowledgements: We gratefully acknowledge the support by METU (BAP ), TUBİTAK (BİDEP 2211) Scholarship for C.K and the Turkish Ministry of Development for the establishment of BIOMATEN. 48

65 O-BM08 Quantitative characterization of biomaterials and their interaction with living cells by AFM Torsten Müller *,1, Carmen Pettersson 1, Tanja Neumann 1 1 JPK Instruments, Berlin, Germany ograph Keywords: AFM, Cell Adhesion, Force Spectroscopy Introduction: Topography, roughness and mechanical properties of biomaterials are crucial parameters influencing cell adhesion, morphology and mechanics as well as the development of stem cells [1,2,3,4]. AFM is a powerful tool to map mechanical and adhesive properties. Combining these abilities with advanced optical microscopy allows for extensive characterization of biomaterials. Methods: AFM is based on a flexible cantilever stylus that is scanned over the sample. The probesample interaction is converted into sample topography and interaction force. The sensitivity of the detection system and the accuracy of piezo actuators with capacitive sensors allow for resolving structures of less than 1 nm and forces on the pn scale. Different imaging modes can resolve structures of biomaterials. In force spectroscopy mode, interaction forces between the cantilever and any substrate can be investigated. Using Single Cell Force Spectroscopy, cell-substrate or cell-cell interactions can be measured down to single protein unbinding (fig. 1). Results: Using AFM imaging, the nanostructure of biomaterials have been resolved as well as cell alignment on such structures [4,5].SCFS quantified the adhesion force and the contribution of different components, e.g. from the extra cellular matrix of living cells to implant materials as from cochlear implants [6]. Force-indentation measurements on cells using colloidal probes showed a significant effect of micro-patterned substrates on cellular elasticity [2]. F (nn) Setpoint force (2) E Approach (1) Retract (3) Distance (µm) Fig. 1.:Sketch of SCFS experiment. The probe cell is approached to (1) and pressed against the substrate (2) with a defined Setpoint force (F) for a defined time (t). When the cell is separated from the sample (3) interactions like maximum adhesion force (Fmax) and single unbinding events (force jumps (J) and those that are preceded by membrane tethers (T)) are visible in the force distance curve. The contact part of the Approach curve allows for applying elasticity models (E). Discussion & Conclusions: Interaction forces from single molecule unbinding to cell adhesion and analysis of surface and mechanical properties of biomaterials and cells make AFM to a key technology in biomaterial research. Nanomechanical analysis of cells increasingly gains in importance in different fields in cell biology like cancer research [7]. We present a strategy to comprehensively characterize biomaterials as well as their interaction with cells. [1] Elter et al., (2011) Eur Biophys J 40(3): [2] McPhee, (2010) MedBiolComput48(10): [3] Engler et al., (2006) Cell 126(4): [4] Kirmse et al., (2010) J Cell Sci 124(11): [5] Cisneros et al., (2007) Small 3(6): [6] Aliuos et al., (2010) Biomed Tech 55: [7] Cross et al., (2007) Nat Nanotech 2(12):

66 Cell number/c O-BM09 Micropatterned Collagen-Fibroin Films For Guidance Of Adipose Derived Stem Cells E. Sayın 1,3,4, E. T. Baran 4, Vasıf Hasırcı *,1,2,3,4 METU, Departments of 1 Biological Sciences, 2 Biomedical Engineering, and 3 Biotechnology, Ankara, Turkey 4 BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, Ankara 06800, Turkey Keywords: Adipose derived stem cell, cell orientation, micropattern Introduction: Adipose derived stem cells (ADSC) are renewable sources that can be collected from human volunteers multiple times with no site morbidity for tissue engineering of bone [1]. It is known that micro level physical cues can affect cell morphology, alignment, proliferation, and differentiation [2]. Objectives of the present study were to construct collagen-silk fibroin based films to test their suitability for bone tissue engineering. Methods: Films were prepared using collagen type I (C) and silk fibroin (SF) by solvent casting and stabilized by crosslinking with EDC/NHS. In situ degradation was studied gravimetrically in PBS at 37 o C. ADSC viability, proliferation and alignment were determined with live-dead cell staining, Alamar blue assay and phalloidin-fitc and DAPI staining, respectively. Results: Degradation levels of CSF films of collagen, fibroin and their blends after crosslinking were found to be low enough to move into in vitro studies. Except pure fibroin films, degradation rates of all films were faster in the first week and by the end of 4 weeks, films had lost less than 25% of their weight. Live-dead staining showed high ADSC viability on films. Alamar blue assay indicated low initial cell attachment, however, presence of micropillar patterns increased the cell numbers (Fig 1). SEM, cytoskeleton and cell nuclei staining showed that the cells oriented parallel to the channels (Fig. 2). On the pillared surfaces cells stretched between pillars. Day 1 Day 3 Fig. 1. ADSC proliferation on TCPS and collagen/fibroin 2:1 (w/w) films (n=3). Fig. 2. SEM images of ADSCs at day 3 on CSF films. (a) unpatterned, (b) channeled and (c) pillar micropatterned films (x300). Discussion & Conclusions: Due to brittleness of CSF films with high fibroin contents, collagen/fibroin 2:1 (w/w) ratio was selected for in vitro studies and composition was shown to be compatible with ADSC. Higher cell proliferation on micropillar films could be due to increased surface area with respect to unpatterned control and also the physical restrictions imposed. Acknowledgements: This study was supported by METU through BAP project. [1] Mitchell JB, McIntosh K, Zvonic S, et al., (2006). Stem Cells 24: [2] Thian ES, Ahmad Z, Huang J, et al., (2008). Biomaterials 29:

67 O-BM10 Surface modification of biomedical polyurethanes with chitosan for antibacterial and anti-adhesive purpose Filiz Kara 1, Eda Ayşe Aksoy 2,3, Zehra Nur Yüksekdağ 4, Nesrin Hasırcı 3,5, Serpil Aksoy*,1 1 Gazi University, Department of Chemistry, Ankara, Turkey 2 Central Laboratory, Middle East Technical University, Ankara, Turkey 3 BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara, Turkey 4 Gazi University, Department of Biology, Ankara, Turkey 5 Middle East Technical University, Department of Chemistry, Ankara, Turkey Keywords: Antibacterial, chitosan, polyurethane, surface modification Introduction: Bacterial adhesion and biofilm formation on a biomaterial surface and subsequent infectious complications are frequent reason for the failure of many medical devices and implants like cardiovascular implants, catheters and urinary tract access. It is important to improve the antibacterial or anti-adhesive properties of surfaces of biomaterials. There are some physical and chemical techniques which modify the surface without altering the bulk properties. One of them is the coating of the surface with an antibacterial agent such as chitosan (CH) and its derivatives. CH is a non-toxic and biocompatible polymer produced from the deacetylation of chitin. In this study, CH was immobilized on polyurethane (PU) films to prepare an antibacterial and anti-adhesive material for biomedical applications. The films were analyzed for their surface properties, along with antibacterial and anti-adhesive efficiencies. Methods: PU films were synthesized in medical purity from toluene diisocyanate and polypropylene ethylene glycol without using any other ingredients such as catalyst, chain extender, solvent, etc. [1,2]. PU surfaces were activated by oxygen plasma and modified by covalent immobilization of chitosan in two different concentrations. Formation of radicals after the plasma application was detected by ESR. The surface properties of PU and CH immobilized PU surfaces (PU-CH-0.5 and PU-CH-2.0) were examined by ATR-FTIR, goniometer, ESCA, and AFM. The antibacterial and anti-adhesion performances of PU and PU-CH films were tested with S. aureus and P. aeruginosa, the most common microbial pathogens encountered in biomaterial infections by colony counting method and SEM. Results: The oxygen plasma treatment on PU created peroxide radicals having g-value of 2.004, detected by ESR. The water contact angle values of PU-CH films were found to be significantly lower (50 o for PU-CH-2.0 and 30 o for PU-CH-5.0) than pristine PU (90 o ). ESCA analysis showed presence of saccharide unit of chitosan through the absorbances of O-C-O groups. Immobilization of CH increased surface roughness. Both PU-CH 0.5 and PU-CH 2.0 demonstrated strong antibacterial activity for both bacteria types. Bacterial adhesion of P. aeruginosa and S. aureus on both chitosan immobilized surfaces effectively decreased compared to pristine PU films. Discussion & Conclusions: The surface properties of CH immobilized PU surfaces were completely changed and more hydrophilic and rougher surfaces were obtained compared to pristine PU. Control of the surface properties plays a significant role and having antibacterial or anti-adhesive biomaterials is crucial for many medical applications. [1] N. Hasirci and E. A. Aksoy (2007). High Perform Polymer 19: 621 [2] E. A. Aksoy, N. Hasirci (2012) J Biomat. Tissue Eng. 2;

68 O-CB02 R&D strategies in biomaterial production Cansel Öğütçü 1,3, Assoc. Prof. Halil Murat Aydın*,2,3 1 Department of Nanotechnology and Nanomedicine Hacettepe University, Ankara, Turkey 2 Department of Bioengineering, Hacettepe University, Ankara, Turkey 3 BMT Calsis Health Technologies Co., Ankara, Turkey Keywords: Biomaterial Production, Research and Development Introduction: The global market for biomaterials is expected to reach $64.7 billion in 2015 from $25.6 billion in 2008 and rising of the aging population worldwide (20% of the global population expected to be over 60 years in 2050) is one of the driving forces in increased biomaterial research and production [1]. Innovative solutions are needed to meet the patients, health professionals and institutions demands concurrently, in terms of technology, usability and price. Tissue engineering and cell therapies are immerging areas globally to respond these meet and preclinical, clinical and commercial development status are the main milestones of these strategies [2]. Research and development (R&D) departments of medical device manufacturers spend over million dollars each year for new approaches and applications and EU or national funding opportunities are the major supports of these evolving fields. Discussion & Conclusions: R&D strategies are the key components of the biomaterial manufacturers for successful projections. Business plans of these strategies cover business model, financial and commercialization plans of product plan. In addition, regulatory changes and requirements especially in tissue engineering products and cellbased therapies discourage researchers and investors mostly in developing countries. As the first orthobiologic material manufacturer, BMT Calsis Co. adopts an RD strategy including pioneering in its own area, easily handling of the certification processes and good business and investment plans. Acknowledgements: BMT Calsis Health Technologies Co. [1] Global Biomaterial Market ( ), ReportLinker Co., [2] A. Jaklenec, A. Stamp, E. Deweerd, A. Sherwin, R. Langer (2012). Tissue Engineering: Part B. 18(3):


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71 P-BM01 Biomaterial selection for mouse spinal cord injury models using mouse embryonic stem cell-derived neuron-like cells H. Seda Vatansever 1, Mustafa Barutçuoğlu 2, A. Şükrü Umur 2, Nurcan Umur 3, Aylin M. Deliormanlı 4, Hayrunnisa Yeşil 1 Celal Bayar University, Faculty of Medicine, 1 Department of Histology-Embryology, 2 Depatment of Neurosurgery, 3 Vocational School of Health Services, Department of Biochemistry, 4 Faculty of Engineering, Depatment of Material Engineering, Manisa, Turkey A stem cell-based therapy has been increasing over the last decades, not only in the research but also clinical application. Different type of stem cell sources can be used for tissue engineering, however, further differentiation of stem cells are depend on source of the cells and culture condition. When the cells can be possible use in clinical application, the ability of cell live in vivo condition, biomaterials can be support to their survival in there. In order to reach these goals, biomaterial selection for differentiated cells and using in regenerative medicine are play important role for efficient treatment. Spinal cord injury is very dramatic disease and when the motor neurons are damaged, it could not be possible treatment without any disability. To replace the neuron and/or neuroglia cells in neurodegenerative disease, cell therapy may be effective. In our study, we investigate using bioactive glass scaffold for transferring the mouse embryonic stem cell-derived neuron-like cells into experimental mouse spinal cord injury models. Mouse embryonic stem cell line was purchased from the Celal Bayar University, Medical Faculty, Histology and Embryology Department stocks. They were cultured in embryonic stem cell culture medium (ESM) [DMEM containing 4500 mg/l glucose and sodium pyruvate, 15% fetal bovine serum, 1% l-glutamine, 1% penicillin/streptomycin, 0.1 mm non-essential amino acid, 10 6 M β-mercaptoethanol and 1000 IU/ml leukemia inhibitory factors (LIF)] on mitomycin-c treated feeder layer cells. For differentiation, the hanging drop method was used. For neuronal differentiation, the cells were cultured on fibronectin coated plate adding N2+bFGF in ESM for 2 weeks. They were then collected, some of the cells were cultured on chamber slide for immunohistochemical analyses, rest of them were cultured on %5 CE added-13-93b3 bioactive glass. After 24 h, the scaffold with cells was transferred at spinal injured mouse. Animals who had laminectomy+trauma were divided in three groups; first group was sham group and had no treatment. Second group was control group after injury scaffold without cells were implanted at injury site. Third group was experimental group after injury scaffold with differentiated cells were implanted in injury site. All animals were sacrificed after 4 weeks of transplantation. For immunohistochemical analyses the cultured cells and tissues were fixed with 4% paraformaldeyde and 10% formalin solution, respectively. The distributions of β3tubulin, GFAP, O4 and MAP2 were analyzed using indirect immunohistochemical analyses. Positive immunoreactivites of cells were detected after 2 weeks culture in neuronal differentiation culture medium. However, immunoreactivity of both β3tubulin and MAP2 were detected strongly than other markers. In tissue sections, the immunoreactivities of β3tubulin and MAP2 were more detectable in group 3. Less immunoreactivity of O4 was also observed in all groups. Bioactive glass scaffold were useful for neuron-like cells transferring on in vivo condition, because of injured neuronal cells were expressed normally several neuronal markers after transplantation, this biomaterials may be use for spinal injury treatment. 55

72 P-BM02 Chitosan nanocomposite microspheres as a controlled drug delivery system Seda Güneş 1, Funda Tıhmınlıoğlu*,2 1 Izmir Institute of Technology, Biotechnology & Bioengineering Pr.,İzmir, Turkey 2 Izmir Institute of Technology, Chemical Engineering Dep, Izmir, Turkey Keywords: Chitosan microsphere, drug delivery systems, nanoclay Introduction: In therapeutic applications, the efficiency of a drug depends on targeting specific body parts and maintaining a desired concentration level for longer period of time. In recent years, intercalated polymer/nanoclay nanocomposites are used as drug carriers, though the nanoparticulate drug delivery systems have numerous advantages over the conventional dosage forms which include improved efficacy, reduced toxicity and improved patient compliance. Nanoclays are widely used in pharmaceutical technology such as drug delivery, drug excipient. Montmorillonite (MMT) is a kind of clay mineral with a large specific surface area; it exhibits enhanced gel strength, good adsorbability, cation exchange capacity, mucoadhesive capability to cross the gastrointestinal (GI) barrier and drugcarrying capability. Among several drug delivery systems, chitosan microspheres are promising in site-specific drug release systems such as gastric retentive delivery systems. Since the middle ages, essential oils have been widely used for medicinal, pharmaceutical and food applications. Therefore, use of encapsulated essential oils is a promising idea for food supplement or medicinal therapy. Nowadays, microspheres containing silicates have particular interest as the encapsulating agents for protecting the active substance and controlled release. The aim of this study is to develop a novel new drug delivery systems containing essential oil which has the potential to be used in GI systems. solution was added into the dispersion and sonicated. After sonication essential oil was added into the under continuous stirring. Microspheres were obtained by spray drying. After production of micropheres by spray drying, microspheres were characterized by SEM, STEM, XRD, and Zeta Potential for determination of particle size distribution and surface charges of microspheres and clay dispersion. Drug release profiles from chitosan based microspheres were also examined. Discussion & Conclusions: Essential oil successfully loaded into chitosan/nanoclay microspheres by spray drying method. The particle size of microspheres was found as approximately 1-2 μm. OH stretching, CH stretching, amide II and Si-O bonds were determined by FTIR. The intensity of the Si-O bond was increased depending on the increased clay amount. XRD and STEM results showed that good dispersion of 3% and 5% of clay content in chitosan matrix. It is found that microspheres have positive surface charge due to nanoclay and chitosan. This result provides mucoadhesive property and therefore, it is useful for GI located drug delivery. [1] Bakkali F., Averbeck S., Averbeck D., Idaomar M. (2008). Food and Chemical Toxicology 46: [2] Ha, J. U., Xanthos, M. (2011). International Journal of Pharmaceutics 414: Methods: Essential oil loaded chitosan nanoclay microspheres were prepared by the following procedure. 1% chitosan was dissolved in acetic acid solution, then OMMT (1%, 3%, 5% w/w) 56

73 P-BM05 Mechanical properties of the sol-gel derived alumina-bovine hydroxyapatite composites Azade Yelten*,1, Suat Yilmaz 1 1 Istanbul University, Department of Metallurgical and Materials Engineering, Istanbul-Turkey Keywords: alumina, biocomposites, hydroxyapatite, mechanical properties, sol-gel Introduction: Sol-gel technology is an ideal way to produce powder materials with high chemical purity. Alumina (α-al 2O 3) is commonly used in strength-based biomaterial applications due its bioinert character. Although hydroxyapatite (HA, Ca 10(PO 4) 6(OH) 2) can form biochemical bonds with body tissues, its solo usage is not suitable because of its brittle nature [1]. Methods: Boehmite sol was produced via the solgel procedure. Aluminum isopropoxide (AIP, Al(OC 3H 7) 3) was used as the starting material and hydrolyzed in a system where distilled water/aip molar ratio was 100. BHA powders (bovine hydroxyapatite) obtained from bovine bones were added as 10, 20, 30 and 50 wt.% of AIP to the boehmite sol and mixed. Partially homogeneous dispersion of BHA powders in the sol was provided utilizing from sodium alginate (Na-alg, NaC 6H 7O 6). Following gelation at 110 C for 3 hours, heat treatment was applied to the gelated mixtures at 1300 C for 2 hours and eventually composite powders comprised of α-al 2O 3 with high purity and crystallinity, HA and tricalcium phosphate (TCP, Ca 3(PO 4) 2) phases were obtained. Chemical analyses of the composite powders were done with a Rigaku D/Max-2200/PC branded x-ray diffraction (XRD) device. Composite powders were coded as 1300AH10, 1300AH20, 1300AH30 and 1300AH50 where 1300 stands for the heat treatment temperature, A for the α-al 2O 3 and H for the BHA phase while 10, 20, 30 and 50 for the BHA powder amount (wt.%) added to the sol. Cylindrical pellets were prepared from each composite powder group by pressing and sintering at 1300 ºC for 2 hours. Cold compression tests were performed on the pellets by using a Devotrans branded DVT FU model device. Fracture surface characterizations were carried out with a Jeol branded JSM 6335F (field emission) model scanning electron microscope (SEM) [2]. Results: Compression test results showed that the compression strength and Young s modulus values of the composite pellets increased with increasing amount of BHA powder added to the boehmite sol. 1300AH50 sample exhibited the highest average compression strength, 114 MPa [2]. Discussion & Conclusions: Compression test results were considerably lower than that of the α- Al 2O 3 phase itself. It is thought that the ceramic bonds formed between α-al 2O 3 and BHA phases are not strong enough due to insufficient sintering time and temperature. Fracture surface SEM images indicated that the fractures occurred at the grain boundaries, α-al 2O 3 crystals could not grow and large pores and gaps exist between the α-al 2O 3 and BHA grains [2]. Acknowledgements: This work was financially supported by the Research Fund of Istanbul University with project no: [1] B.D. Ratner, A.S. Hoffman, F.J. Schoen, J.E. Lemons, 2004, Biomaterials Science An Introduction to Materials in Medicine, Elsevier Academic Press. [2] A. Yelten, 2010, Properties and Characterization of Alumina-Bovine Hydroxyapatite (BHA) Composites Produced by Sol-Gel Method, M.Sc. Thesis, Istanbul University. to the boehmite sol. 57

74 P-BM04 Cell Viability of Keratinocytes on Electrospun Spirulina/PCL Composites Cenk Çelik 1, Cansu Görgün 2, Aylin Şendemir Ürkmez 1,2* 1 Ege University Bioengineering Department, Bornova, Turkey 2 Ege University Department of Stem Cell, Bornova, Turkey Keywords: Spirulina, poly-caprolactone, electrospinning, BMSC, keratinocyte Introduction: Spirulina platensis is a microalgae that can survive in alkaline media and had been consumed since the Aztecs as a food source due to its high protein content [1, 2]. Recently, it also draws attention for biofuel production, as pollution control agent, drug active substance and in the biomedical field. As it is thought to have anticancer, anti-viral, anti-bacterial and antiinflammatory properties [3]. The aim of this study is to form a natural, biocompatible, biodegradable and spinnable polycaprolactone (PCL)/Spirulina biocomposite tissue engineering scaffold benefiting from the indicated properties and evaluate the cell viability on these scaffolds. Methods: For the electrospinning of the PCL/Spirulina composite firstly, PCL solution was prepared. As solvent, DMF and DCM was mixed at 1:1 ratio to dissolve 12% (w/v) PCL 12% (w/v) and mixed overnight on a magnetic stirrer. After homogenization is achieved 4% (w/v) powdered Spirulina was added to the solution and mixed thoroughly. PCL and PCL/Spirulina composites were spun onto 1,6 cm diameter cover glasses placed on aluminum foil. The scaffolds were sterilized via UV radiation for 3 hours. Adipose derived human keratinocytes were seeded onto both PCL and PCL/Spirulina biocomposite scaffolds (1.6 x10 6 cells/ml) to evaluate cell viability and cultured in Dulbecco s MEM with 10% fetal bovine serum (FBS). Survival of cells for first, fourth and seventh days on PCL and PCL/Spirulina biocomposite scaffolds was investigated by MTT cell viability test. Results: The results of viability tests were evaluated and ANOVA statistical analysis was carried out (p<0.05 Tukey s and Fischer s). Fig. 1 Histogram graphic of keratinocyte cells viability. Here, blue bar is referred to control group, red bar is keratinocyte cells seeded onto PCL scaffolds and green bar is keratinocyte cells seeded onto PCL/Spirulina : [1] Capelli, B., Cysewski, G.R. and Moorhead, K., 1993, Spirulina Nature s Superfood, Cyanotech Corporation, Hawaii, [2] Conk-Dalay, M. and Ozdemir, G., 2008, Spirulina and Antibacterial Activity, Gershwin, M.E., Belay, A. (Ed.). Spirulina in Human Nutrition and Health, CRC Press, Boca Raton, 247. [3] Ozdemir, G, Karabay, NU, Conk-Dalay, M, Pazarbasi, B, 2004, Antibacterial activity of volatile component and various extracts of Spirulina platensis, Phytotherapy Research, 18:

75 P-BM05 Optimization of gelatin films crosslinked by EDC/NHS and genipin methods as cell attachment substrates Çiğdem Demirkaya 1, Jennifer Patterson *,2,3 1 Department of Bioengineering, Ege University, Izmir, Turkey 2 Department of Metallurgy and Materials Engineering and 3 Research Division Prometheus, KU Leuven, Leuven, Belgium Keywords: Chemical crosslinking, EDC/NHS, gelatin films, genipin Introduction: Gelatin is a natural material derived from the hydrolysis of collagen, a primary protein component of the extracellular matrix (ECM), and they have an almost identical composition. Due to its biological origin, biodegradability, and biocompatibility, gelatin has been widely used in the pharmaceutical and medical fields. However, as with collagen, the poor mechanical properties of gelatin limit its possible application as a biomaterial. For long-term biomedical applications, gelatin has been crosslinked, which improves both the thermal and mechanical stability of the material. Several crosslinking methods have been developed, and bi-functional reagents, such as glutaraldehyde and diisocyanates, as well as carbodiimides, polyepoxy compounds, acyl azide, and genipin are common chemicals used for crosslinking[1]. Methods: Gelatin films were made from different concentrations and different volumes of type A and type B gelatin. Two different genipin crosslinking methods were tested, with varying incubation times. To prevent dissolution of the films, genipin was prepared in 70-90% ethanol solutions. For 1-Ethyl- 3-(3-dimethylaminopropyl) carbodiimide/n- Hydroxysuccinimide (EDC/NHS) crosslinking, different concentrations and volumes of chemicals, in both water and ethanol solutions, were used. Films were incubated the EDC/NHS solutions for 18 hours at 4 C. Crosslinked gelatin films were used as a cell attachment substrate for the chondrogenic cell line, ATDC5 cells. The Presto Blue metabolic activity assay for cell proliferation, Live/Dead assay for cell viability and Picrosirius Red staining for gelatin/collagen were performed. Results: The Presto Blue metabolic activity assay showed that ATDC5 cell proliferation on films crosslinked with EDC/NHS in aqueous solutions was similar to cells grown on tissue culture plastic; however, the genipin crosslinking and EDC/NHS in ethanol methods had a slightly cytotoxic effect. After Picrosirius Red staining, it was observed that films incubated in higher concentrations of EDC/NHS were less swollen. The films that were made from 2% gelatin and crosslinked via genipin were more swollen than other genipin-crosslinked films during cell culture. Discussion & Conclusions: In this work, the effect of crosslinking chemistry on cell attachment and proliferation on gelatin films was examined. According to the results, for both the efficiency of crosslinking and cell assays, type A gelatin had more successful results than type B gelatin. Type B gelatin films were swollen in all studies and detached from the glass substrate. This situation negatively effected cell attachment and proliferation in cell culture studies. Although cells grown on films crosslinked with genipin has less metabolic activity than those with the EDC/NHS method, high numbers of viable cells were attached on films crosslinked with both methods. Characterization of the extent of crosslinking as well as the mechanical properties of the films is ongoing. [1] A. Bigi. et al.(2002) Biomaterials 23:

76 P-BM06 Osteogenic differentiation of marrow stromal cells in hydrolytically degradable PEG based hydrogels Seyedsina Moeinzadeh 2, Danial Barati 2, Ozan Karaman 1,2, Samaneh K. Sarvestani 2 Esmaiel Jabbari *,2 1 Department of Bioengineering, Ege University, Bornova, Izmir, Turkey 2 University of South Carolina, Columbia, SC, USA Keywords: Hydrogels, Marrow stromal cells, Osteogenic differentiation Introduction: Hydrogels with wide range of degradation rates and mechanical properties are needed in many areas of regenerative medicine. Polyethylene glycol (PEG) based hydrogels due to their non-immunogenic and inert nature are being used extensively as matrices for cell encapsulation. However, their use for in vivo applications is severely limited by their non-degradability. The degradation rate and mass loss profiles are one of the most significant scaffold criteria while designing in-vivo tissue engineering scaffolds. Consequently, if the degradation profile of the scaffold appropriately designed, the scaffold would degrade at the similar rate of the formed natural tissue. In order to impart degradation into PEG hydrogels, short segments of a degradable monomer can be incorporated into PEG macromonomers. The objective of this work was to investigate the response of marrow stromal cells (MSCs) to encapsulation in degradable star poly(ethylene glycol-co-lactide) acrylate (SPELA) hydrogels. Methods: The SPELA macromonomer, MSCs, and integrin binding peptide (Ac-GRGD) were mixed and cross-linked by UV polymerization and cultured in osteogenic media for 21 days. SPELA hydrogels with compressive moduli as high as 500 kpa were synthesized. In 4 weeks, the SPELA hydrogels with 2 and 4 lactides per macromonomer arm had 35% and 90% mass loss, respectively, compared to <5% mas loss for non-degradable PEG hydrogel. At each time point, samples were used for determination of extent mineralization and mrna analysis. Results: According to the live-dead staining results, MSCs encapsulated in SPELA and PEG hydrogels with constant compressive modulus but different degradation profile did not have a significant effect on cell viability. ALP activity of all groups increased from day 7 to 14 and then decreased after 28 days with mineralization. At day 14, ALP activity of SPELA was significantly higher than PEG hydrogels. Calcium content of all groups had an increasing trend with time. Furthermore, at day 28, calcium content of SPELA was significantly higher than that of PEG group. In addition, Alizarin Red staining results showed extend mineralization in SPELA hydrogels. Discussion & Conclusions: The results demonstrated that degradation of SPELA gels contributed significantly to mineralization with SPELA 2.3-fold higher mineral deposition compared to non-degradable PEG hydrogel. The SPELA hydrogel is attractive as inert, degradable, remodelable, and injectable matrix for cell delivery in bone tissue engineering applications. Acknowledgements: This work was supported by grants from the National Science Foundation under Grant No. CBET and CBET , the National Institutes of Health under Grant No. R03 DE A1, and the Arbeitsgemeinschaft Fur Osteosynthesefragen (AO) Foundation under grant the Foundation under grant no. C10-44J. [1] Moeinzadeh, S., Barati, D., He, X., Jabbari, E., (2012) Biomacromolecules. 13 (7), [2] Moeinzadeh, S., Jabbari, E., (2012). J Phys. Chem. B. 116 (5),

77 P-BM07 Porous pullulan microcarriers for osteochondral tissue regeneration Hazal Aydoğdu 1, Dilek Keskin 1,2,3, Erkan Türker Baran 3, Ayşen Tezcaner *,1,2,3 1 1 METU, Department of Biomedical Engineering, Ankara, Turkey 2 METU,, Department of Engineering Sciences, Ankara, Turkey 3 METU BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Ankara, Turkey Keywords: microspheres, pullulan, silk fibroin coating, tissue engineering, water-in-oil emulsion Introduction: Osteochondral defects are localized joint damages in which the cartilage and underlying bone have been disrupted due to accidents and diseases. For osteochondral defects there is a need for a simultaneous regeneration of cartilage and subchondral bone. Tissue engineering is a rapidly developing field that uses a bottom-up approach to synthesize engineered tissues. In the current study, a three-dimensional hydrogel based microcarrier can be developed by using porogen leaching and surface coating techniques. We aim to create macroscopic tissue constructs carrying chondrocytes and osteoblasts seperately within pullulan hydrogel microspheres that can be injected into the defect site for osteochondral tissue regeneration. Methods: Pullulan microspheres were synthesized through water-in-oil emulsion crosslinking of microdroplets by sodium trimetaphosphate. Pore formation in microspheres was achieved by using different amounts of calcium carbonate granules about 20 m in size. Calcium carbonate was then removed by hydrochloric acid leaving pores behind. Microspheres were also coated with 1% silk fibroin (SF) via reacting primary amine groups of SF with aldehyde groups formed on pullulan microspheres. FITC labelled SF coating on pullulan microspheres were analyzed by fluorescence microscopy(fig.1). Morphologies and average diameters of crosslinked microspheres were assessed with microscopic techniques. SF coated and uncoated microspheres are cultured with sarcoma osteogenic cells to see the effect of coating on cell-material interactions. Results & Discussion: Pullulan microspheres, fabricated by emulsion at 500 rpm, have spherical shape and porous structure with an average diameter of 115 µm with 30% porogen calcium carbonate. The microsphere size was found to be homogenously distributed. The cell culture study showed that SF coated microspheres not only represented improved mechanical properties but also had better surface properties with respect to cytocompatibility. The cells had more tendency to interact with the SF coated microspheres than uncoated microspheres as SF coating add cell adhesive protein layer on hydrophilic hydrogel microspheres. Fig. 1. Fluorescence microscopy image of FITC labelled fibroin coated pullulan microspheres. Conclusions: We introduce data to demonstrate that hard tissue cells can be encapsulated in porous pullulan microspheres after coating with SF. The combination of the cell-seeded microspheres generates an injectable system that can be applied to osteochondral defect sites for an improved response by accelerating regeneration of both sites. 61

78 P-BM08 Synthesis, radiolabeling and bioevaluation of an imidazolium TFSI salt Onur Alp Ersöz 1, Hale Melis Soylu 2,*, Fatma Yurt Lambrecht 1, Kasim Ocakoglu 3 1 Department of Nuclear Applications, Institute of Nuclear Science, Ege University, Bornova, 35100, Izmir, Turkey. 2 Department of Biomedical Technologies, Institute of Natural and Applied Sciences, Ege University, Bornova, 35100, Izmir, Turkey. 3 Advanced Technology Research & Application Center, Mersin University, Ciftlikkoy Campus, TR Mersin, Turkey. Keywords: bis(trifluoromethane)sulfonimide, I-131, imidazolium salt, molecular imaging Introduction: There are three basic methods which are using generally for treatment cancer. These are surgery, chemotherapy and radiotherapy. Additionally, supporting medicine (immunotherapy and biologic therapy) uses for treatment of cancer. In the cell culture studies with bis(trifluoromethanesulfonyl)imide (TFSI) extract show that they have been employed in some tumor cell lines (mammalian cells including rat leukaemia cell line IPC-81, cell line HT-29 and CaCo-2 and HeLa). This study aims to investigate in vivo study about pharmacokinetics of octyl-bis(3- methylimidazolium)- di(bis(trifluoromethane)sulfonimide). Methods: In current study, octyl-bis(3- methylimidazolium)- di(bis(trifluoromethane) sulfonimide) was synthesized starting from 1- methylimidazole and 1,8-diiodooctane. After obtaining imidazolium-iodide salt, the anion (iodine) was exchanged with bis(trifluoromethane)sulfonimide (TFSI) in order to yield the final product, imidazolium-tfsi salt. And then the imidazolium-tfsi salt was radiolabeled with I-131 by using iodegen method. Optimization of parameters was investigated such as amount of oxidizing agent, ph and reaction time. Quality controls were performed by using radio thin layer chromatography (RTLC) method. After optimization of radiolabeling conditions of TFSI, serum stability study of radiolabeled compound was carried out. Results: According to results of efficiency of radiolabel compound was 91.7±5 %. The optimum conditions 62 were determined as amount of iodogen: 1mg, reaction ph: 7 and reaction time 30 min. On the other hand radiolabeled compound was observed to be stable in 4h. Discussion & Conclusions: The desired efficiency was obtained succesfully. The bioevaluation of radiolabeled compound and cell culture studies are continued. [1]Calin M A, Parasca SV, (2006) Mater, J. Optoelectronics Avdan, 8, [2]Salter R, Bosser I, (2003) J Label Compd Radiopharm, 46, [3]Lee J, Lim KT, (2012) Drug Chem Toxicol, 35(3), [4]Wang X, Ohlin CA, Lu Q, Fei Z, Hu J, Dyson PJ, 2007, Green Chem. 9,

79 P-BM09 Polyethylene oxide nanofibers: effects of electrospinning and crosslinking conditions Murat Şimşek *,1, Soner Çakmak 1, Menemşe Gümüşderelioğlu 1,2 Hacettepe University, Nanotechnology and Nanomedicine 1, Chemical Engineering 2, Ankara, Turkey Keywords: electrospinning, nanofiber, polyethlylene oxide, UV-crosslinking. Introduction: In electrospining method, many processing parameters must be considered to produce desirable polymeric nanofibers. Although various methods have been employed to crosslink PEO from different forms, UV induced crosslinking technique has many advantages [1, 2]. In this study, the effect of electrospinning conditions on morphology and diameter of electrospun PEO nanofibers were investigated. Crosslinking studies of PEO nanofibers including benzophenon (Bp) or pentaerythritol triacrylate (PETA) in the presence or absence UV irradiation were also performed. Methods: PEO nanofibers were obtained at given conditions in Table 1. The irradiation of PEO samples consisting of Bp or PETA was carried out at room temperature in dark with two different UV light sources emited a light at distinct wavelength. Dynamics swelling experiments were realised in order to determine the most appropriate crosslinking condition. Surface morphologies and chemical structure of fibers were analysed by SEM and ATR-FTIR. Results: Nanofibers obtained from all voltages had smooth and uniform morphology being similar to each other (Fig. 1 a). Fibers not exhibiting typical morphology were obtained with increasing polymer concentration up to 7% and flow rate up to 1 ml sa - 1 (Fig 1 b). Fiber diameters ranging from 156 to 412 nm decreased gradually with increasing voltage. There was an increase in fiber diameter with increasing flow rate. The effect of the distance on fiber diameter was not distinctive. The most appropriate crosslinking condition was gained with the nanofibers incorporating 10% (w/w) of PETA drying for 8 days. Besides PEO- PETA nanofibers could be crosslinked via UV12, they could be crosslinked directly by PETA in the absence of UV12 in room condition. Table 1. Electrospinning conditions investigated for obtaining PEO nanofibers. Discussion & Conclusions: In conclusion, this two step process including electrospinning and UVcrosslinking of PEO can be used as an effective coating method for minimizing metalic implantrelated infection risk. Figure 1. SEM images of fibers from %8 wt of PEO at 15 cm. (a) 0.5 ml sa -1,12 kv and (b) 1 ml sa -1, 14 kv. [1] Savaş H. Güven O International Journal of Pharmaceutics 224: [2] Doycheva M. Petrova E. Stamenova R. Tsvetanov C. Riess G Macromolecular Materials and Engineering 289:

80 P-BM10 Collagen chemical bonding of the silicone hollow fiber surface to enhance endothelial cell attachment Tohid Hajibabaei 1,2, Jhamak Nourmohammadi* 2,3, Ghassem Amoabediny 1,2, Nasim Salehi-Nik 2, Seyyed Hasan Jafari 1, Khosrow Mottaghy 4 1 Dept. of Polymer, Faculty of Engineering, University of Tehran, Tehran, Iran 2 Dept. of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, Iran 3 Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran 4 Dept. of Physiolology, RWTH Aachen University, Aachen, Germany Keywords : APTES, endothelial, hydrophobicity, PDMS, vascular tissue engineering. Introduction : Silicone rubbers are widely used in biomedical applications due to their good biocompatibility as well as mechanical properties [1, 2]. However, their high hydrophobicity caused poor cell attachment which limits their application in the biomedical engineering [3]. Methods : In this work, we modified (PDMS) small diameter hollow fibers (d=2mm) by firstly activated by using gentle treatment of O 2 plasma for 40s. Immediately, following the oxygen plasma activation, the amine groups were covalently bonded to the surface of hollow fibers by immersing the polymer in a (3-amino-propyl) trimethoxysilane (APTES) solution for 24h. Afterwards, the modified surface was covalently coated with collagen protein. Scanning Electron Microscopy (SEM) and contact angle (CA) were used to characterize the modified surface of PDMS hollow fibers and cell attachment. Results : The contact angle data from the virgin and modified specimens are shown in Fig.1. SEM images of endothelial cell attachment on the pristine and collagen coated PDMS surface are shown in Fig.2. It is clearly obvious that the endothelial cells attached and proliferated on the collagen coated surface. Fig. 2. (a) SEM of endothelial cell attachment on the not modified surface (b) SEM of endothelial cell attachment on the modified surface Discussion & Conclusions : The results of this study show that collagen protein was covalently bound to the silicon small diameter hollow fibers and consequently the human umbilical vein endothelial cells (HUVECs) were successfully attached to the hollow fiber surfaces. Accordingly, the modificated PDMS hollow fibers could be useful for applying in vascular tissue engineering. Fig. 1. water contact angle measurement of (a) not modified (b) modified surfaces As indicated in Fig.1, the untreated surface exhibited a hydrophobic nature (Ɵ=112 o ) Compared with the more hydrophilic treated surface (Ɵ=70 o ). : [1] Donghee Lee. (2012). Sensors and Actuators B: Chemical 162: [2] Hui Taek Kim. (2011). Microelectronic Engineering 88: [3] Joong Yull Park. (2012). Sensors and Actuators B: Chemical 173:

81 P-BM11 Effect of Mg addition on electrochemically deposited CaP coatings on Ti6Al4V substrates U. Tiric *,1, B. Bakın 1, G. Ungan 1, F. Ak Azem 2, I. Birlik 2 1 Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Buca, Izmir, Turkey 2 Dokuz Eylul University, Department of Metallurgical and Materials Engineering, Buca, Izmir, Turkey Keywords: Bioactivity; CaP coatings; electrochemical deposition; Ti alloy Introduction: Titanium and titanium based alloys are preferred materials for load bearing implants and the properties of titanium surface are important variable in implant design. Surface modifications are widely used to adjust the properties of titanium surface to the specific needs of the medical applications. In this study, surface modification of Ti6Al4V substrates was applied by electrochemical deposition of CaP coatings. Incorporation of Mg ions into the CaP structure is of great interest for the developing artificial bones [1]. The purpose of the study is to investigate bioactivity properties of produced CaP coatings in simulated body fluid (SBF). Methods: Brushite (DCPD) coatings on Ti6Al4V substrates were deposited in the mixed solution of calcium nitrate tetrahydrate (Ca(NO 3) 2.2H 2O), ammonium dihydrogen phosphate (NH 4H 2PO 4), magnesium chloride (MgCl 2) and distilled water. Coatings produced without Mg and with the amount of 10 wt%, 20 wt% and 40 wt% Mg content were named as Mg-0, Mg-1, Mg-2 and Mg-3, respectively. The simulated body fluid (SBF) was prepared according to Kokubo s recipe [2]. The samples were soaked in the SBF solution using the sterile polyethlene beaker for 1, 4, 7, 14 and 28 days at 36.5±1.5 C. Results: The deposited samples were soaked in SBF in order to observe apatite precipitation with time variation. The soaking period was varied from 0 day up to 28 days. The samples after soaking in SBF were examined by using SEM coupled with EDS. Results are shown in Fig. 1. Fig. 1. SEM images of sample Mg-2 (a) before and after soaking in the SBF solutions for (b) 1 day, (c) 4 days, (d) 7 days, (e) 14 days and (f) 28 days. The number of agglomerates increases with increased soaking time. Additionally, EDS results indicate that Ca/P ratios of the samples increases after soaking in SBF. Discussion & Conclusions: After 1 day of immersion plate-like structure was still partially obvious in the top view. But some floccules appeared on the surfaces. After 7 days of immersion these floccules amount increased greatly and the plate edge became blunt. They contacted each other with small gaps and plate-like structure characteristic disappeared completely [3]. These results are in agreement with the findings of Liu et al. study. Acknowledgements: This work was supported by TUBITAK (The Scientific and Technological Research Council of Turkey) (No. 112R020). [1] Kanchana P., Sekar., C., (2012). J. Min. & Mater. Character.& Eng. 11: [2] Kokubo T., Takadama H. (2006). Biomaterial 27: [3] Liu S., Liang C., Wang H., Qiao Z. (2012). Int. J. Electrochem. Sc. 7:

82 P-BM12 Corrosion properties of electrodeposited CaP coatings with different PVA addition T. Koc *,1, G. Ungan 1, F. Ak Azem 2, A. Cakır 2 1 Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Buca, Izmir, Turkey 2 Dokuz Eylul University, Department of Metallurgical and Materials Engineering, Buca, Izmir, Turkey Keywords: electrochemical deposition, hydroxyapatite, PVA, Ti alloy Introduction: Metallic biomaterials titanium and its alloys are widely used as implant materials in orthopedic and dental prosthesis because of their superior strength, biocompatibility, bioinertness, and corrosion resistance [1, 2]. Many surface treatment techniques have been used to improve their biocompatibility. Hydroxyapatite and some other calcium phosphate bioceramics have been widely used in biomedical field as implant materials due to its excellent biocompatibility and tissue bioactivity properties. The CaP bioceramic coatings on metal substrates have been studied by many methods. The electrochemical deposition of calcium phosphate bioceramic coating has currently attracted considerable attention because of the outstanding properties [3]. It is known that polymeric gels and films, such as polyvinyl alcohol (PVA), have attracted great attention for various applications because of their ease of preparation, excellent chemical resistance and physical properties, biocompatibility and low price. Methods: Electrochemical deposition of calcium phosphate coatings on titanium substrates was performed with current densities at -2.5, -5 and ma/cm² for 60 min, at 80 C. Different amounts polyvinyl alcohol (PVA) is added to the electrolyte during the deposition process (Table 1). Table 1. Abbreviation of the coatings. PVA Addition Current density (ma/cm 2 ) No addition S1 S2 S (vol. %) S4 S5 S (vol. %) S7 S8 S9 Results: Figure 1(a) and (b) show the cyclic polarization plots of Ti6Al4V substrate and produced coatings 66 XRD, FTIR and SEM were used to identify the chemical and morphological properties of coatings. Additionally, corrosion properties of the coatings were studied in Ringer s solution at 37 C. Results: The results showed that homogeneity of the coatings morphology improved with addition of PVA to the electrolyte (Fig. 1). (a) (b) (c) Fig. 1. SEM micrographs of the coatings in higher magnification (a) S1 (b) S3 (c) S9. Furthermore, addition of PVA changed the corrosion properties of coatings when compared to coatings produced without PVA addition (Fig. 2). Fig. 2. Cyclic polarization curves of Ti6Al4V alloy and (a) S3, S6, S9 and (b) S7, S8, S9. Discussion & Conclusion: As a result, when the current density changes from -2.5 ma/cm 2 to ma/cm 2 for each PVA addition conditions, improvements were observed in the corrosion resistance of the coatings. [1] Lopes M.F., Gutierrez A., Jemenez J.A. (2002). Electrochemica Acta 47: [2] Liu D-M, Yang Q., Troczynski T. (2002). Biomaterials, 23: [3] Rakngarm A., Mutoh Y. (2009) Materials Science and Engineering C, 29:

83 P-BM13 Investigation of corrosion properties of electrochemically deposited Mg substituted CaP coatings on Ti6Al4V substrates B. Bakın *,1, U. Tiric 1, G. Ungan 1, I. Birlik 2, F. Ak Azem 2 1 Dokuz Eylul University, The Graduate School of Natural and Applied Sciences, Buca, Izmir, Turkey 2 Dokuz Eylul University, Department of Metallurgical and Materials Engineering, Buca, Izmir, Turkey 1 Institution Name, State and Country Keywords: CaP coatings; corrosion; electrochemical deposition; Ti alloy Introduction: Titanium and its alloys are used as implant materials because of their excellent mechanical properties. Ti and its alloys are bioinert. Therefore, calcium phosphate coating has been widely applied on Ti and Ti alloys implants to improve their biocompatibility properties. Several calcium phosphate coating techniques have been used as plasma spraying, biomimetic deposition, sol-gel, and electrochemical deposition. The electrochemical deposition has a variety of advantages such as low process temperature, ability to deposit on porous or complex shape of substrate, low cost and easiness of thickness control [1]. Substitution of cations like K +, Na +, Zn 2+, Mn 2+ and Mg 2+ in the apatite structure to mimic natural bone has received much attention to take advantage of their roles in bone metabolism, promoting catalytic reaction and controlling biological functions [2]. Methods: CaP coatings were electrochemically deposited on Ti6Al4V substrates under -1 ma/cm 2 current density for 1 h by galvanostatic technique. Coatings produced without Mg and with the amount of 10 wt%, 20 wt% and 40 wt% Mg content were named as Mg-0, Mg-1, Mg-2 and Mg-3, respectively. The surface morphology investigation and the element analysis of the coatings were carried out by using a SEM coupled with EDS. The phase analyses of the coatings were analyzed by XRD. The chemical composition of the deposited coatings was analyzed by FTIR. The corrosion measurements were carried out using a potentiostat/galvanostat system in SBF (simulated body fluid) solution at 37 C. Results: Both needle-like and plate-like structures were observed in all coatings as shown Fig. 1. The cyclic polarization curves of substrate and all of the coatings were given in Fig. 2. The most important parameters such as corrosion potential (E cor), breakdown potential (E b) and current density (i cor) values obtained. (a) (b) (c) (d) Fig. 1. SEM micrographs of the produced coatings (a) Mg-0 (b) Mg-1 (c) Mg-2 and (d) Mg-3. Fig. 2. Polarization curves of the samples in SBF solution. Discussion & Conclusion: These results indicate that obtained brushite coatings on Ti6Al4V substrate improve corrosion performance. Acknowledgements: This study was supported by the TÜBİTAK (The Scientific and Technological Research Council of Turkey), (Project No. 112R020). [1] A. Kar, K.S. Raja, M. Misra. (2006). Surface & Coatings Technology. 201: [2] G. Qi, S. Zhang, K.A. Khor, C. Liu, X. Zeng, W. Weng, M. Qian (2008). Thin Solid Films. 516:

84 P-BM14 In vitro degradation and bioactivity of V +3 doped borate bioactive glass scaffolds Aylin M. Deliormanlı *,1,2, Mohamed N. Rahaman 1 1 Missouri University of Science and Technology, Department of Materials Science and Engineering, and Center for Bone and Tissue Repair and Regeneration, Rolla, Missouri USA 2 Celal Bayar University, Department of Materials Engineering, Turkey Keywords: Bioactive glass, vanadium, scaffolds, bone tissue engineering Introduction: Bioactive glasses are promising scaffold materials for bone regeneration because of their unique ability to convert to hydroxyapatite (HA) in vivo, and their ability to bond with bone and soft tissues [1-2]. Previous studies showed that vanadium can promote bone and teeth mineralization, stimulates osteoblast proliferation and differentiation, and increases mineralization of the matrix and collagen synthesis. It is also a wellknown antidiabetic metal [3]. The aim of this study was to investigate effect of vanadium additions on the in vitro bioactivity of borate based bioactive glass scaffolds. Methods: Un-doped and V +3 doped ( 0.15, 1, 3 wt%) 13-93B3 glasses were prepared by melting related reagent-grade chemicals in a platinum crucible in air for 2 h at 1100 ºC and quenching between cold stainless steel plates. Particles attrition-milled for 2.5 hours using ethanol as the solvent and zirconia balls as the milling media. Porous scaffolds were prepared using a polymer foam replication technique. A slurry containing 35 vol % glass particles was prepared by dispersing the particles in ethanol. A polymer foam with a pore architecture similar to that of dry human trabecular bone was immersed in the slurry to coat the walls of the foam with the slurry. The coated foam was dried and subjected to a controlled heat treatment to decompose the foam and sinter the glass particles into dense network. In vitro degradation and bioactivity of the sintered scaffolds were studied in simulated body fluid (SBF) at 37 C up to 30 days. Results: Figure 1 shows the SEM images of the scaffolds fabricated by polymer foam replication method. Results : Figure 1 shows the images of the scaffolds fabricated by polymer foam replication method. 68 Results : Figure 1 shows the images of the scaffolds fabricated by polymer foam replication method. Results : Figure 1 shows the images of the scaffolds fabricated by polymer foam replication scaffolds fabricated by polymer foam replication method before and after treatment in SBF. Accordingly, scaffolds has a porous structure (78%) and the pore width is in the range of 100 to 500 µm. Results showed that degradation rate of the doped scaffolds in SBF was similar to the undoped scaffolds. Crystalline HA formation was observed on the SBF treated samples. (a) 500 µm (b) Figure 1. SEM images of the sintered 3% V +3 doped scaffolds (a) before and (b) after treatment in SBF for 30 days. Experimental results confirmed that the substituted glasses at all V +3 concentrations maintained their in vitro HA forming ability. Discussion & Conclusions: Based on the degradation studies (weight loss measurements) and characterizations of the SBF treated scaffolds it is possible to conclude that substitutions of vanadium in 13-93B3 glasses did not decrease their in vitro bioactive response. Therefore, borate based bioactive glass scaffolds containing V +3 ions are promising canditates for bone tissue engineering applications. [1] LL. Hench (1998) J Biomed Mater Res. 15: [2] MN. Rahaman, DE Day,BS Bal, Q Fu, SB Jung, LF Bonewald (2011) Acta Biomater 7: [3] V.Mouriño, JP. Cattalini, A R. Boccaccini (2011) J. R. Soc. Interface.

85 P-BM15 Preparation and characterization of electro-spun 45S5 glass nanofibers Aylin M. Deliormanlı *,1 1 Celal Bayar University, Department of Materials Engineering, Manisa, Turkey Keywords: Bioactive glass, electrospinning, nanofibers, tissue engineering applications Introduction: Electrospinning is a unique approach using electrostatic forces to produce fine fibers from solutions or melts. This method has emerged a widespread technology to produce nanofibrous structures for tissue engineering applications [1-2]. Bioactive glasses are promising scaffold materials for bone and soft tissue regeneration. To date, clinical applications of bioactive glasses are limited to those materials synthesized by melting processes. Recently, some bioactive glass compositions including 45S5 Bioglass was synthesized by sol-gel method [3]. However, production of sol-gel derived 45S5 bioactive glass as a nanoscale fiber by means of electrospinning technique has not been reported yet. Therefore, the aim of this study was to prepare 45S5 bioactive glass electro-spun nanofibers for tissue engineering applications. Methods: The composition of the 45S5 bioactive glass is (in mol%) : 46.1% SiO 2, 24.4 % Na 2O, 26.9% CaO and 2.6% P 2O 5. Following chemicals were used as precursors for the sol preparation: tetraethyl orthosilicate (TEOS), triethyl phosphate (TEP), sodium nitrate and calcium nitrate. Each chemical (in the sequence) was added slowly into HNO 3 aqueous solution at room temperature. Prior to electrospining aqueous polyvinyl alcohol solution containing 1% surfactant was added to the sol. The solution was injected at a rate of 1 ml/h to a target plate at 18 kv voltage. Fibers were subsequently heat treated at 700 C for 2 hours. In vitro degradation and bioactivity of the sintered scaffolds were studied in simulated body fluid (SBF) at 37 C up to 30 days. Results: XRD analysis showed that heat treatment temperature was high enough to eliminate the nitrates in the structure of as-spun fibers eliminate the nitrates in the structure of as-spun fibers (see Fig.1) and it did not cause crystalline HA formation on the as prepared glass. Fig. 1. SEM image of the as-prepared fibers. Depending on the processing conditions the electrospun 45S5 glass fibers possessed a range of diameters (150 nm to 600 nm). The sol viscosity and hydrophobicity were the most dominant factors in controlling the fiber diameter and the morphology. In vitro bioactivity studies showed that fibres immersed in SBF was converted to crystalline hydroxyapatite phase. Discussion & Conclusions: Compared to conventional techniques used for the producing microscale bioactive glass fibers, the electrospinning technique allowed the generation of 45S5 nanofibers with much smaller diameters and high surface area. Acknowledgements: The financial support for this research was provided by TÜBİTAK (project 111M766). [1] A. Martins, JV.Araujlo, RL.Reis,NM.Neves (2007) Nanomedicine 6: [2]H-W Kim, H-E Kim, JC.Knowles (2006) Adv Funct.Mater.16: [3]H Pirayesh, J.Nychka (2013) J Am Ceram Soc

86 P-BM16 Use of Bacterial Cellulose Membranes Produced in Static Culture as a Tissue Engineering Scaffold for Dermal Fibroblasts and Mechanical Characterization Zalike Keskin, O. Mert Duman, Mehmet Özgun Özen, E. Esin Hameş Kocabaş, Aylin Şendemir Ürkmez * 1 Ege University, Department of Eng.,Bioengineering Dep. Izmir,Turkey Keywords :Acetobacter xylinum,bacterial Cellulose, Mechanical Strenght, Scaffold Introduction : Cellulose is the most abundant biopolymer on earth, recognized as the major component of plant biomass, and a representative of microbial extracellular polymers. Bacterial cellulose (BC) microfibrils differ from plant cellulose with their high crystallinity, high water absorption capacity and mechanical strength in the wet state with good permeability through porous structure [1,2]. An efficient producer of cellulose is acetic acid bacteria Acetobacter xylinum. Methods: Acetobacter xylinum ATCC strain cultivated on the Hestrin & Schramm (1954) [3] medium (ph ) with static incubation conditions and incubated at 30 C for 7-14 days. Bacterial cellulose membranes were harvested with average 1-3 mm thickness. BS Purification: Bacterial cellulose membranes were washed with distilled water, boiled with 0.1 M NaOH at 70 o C for 2 hours and this process was repeated with distilled water. Finally, membranes were treated with 5% acetic acid for 2-3 seconds to balance ph. Preparation of bacterial cellulose for in vitro applications: Potential tissue scaffolds produced in glass petri dish with distilled water were sterilized by autoclaving at 121 C for 20 minutes. In vitro studies: Dermal fibroblastic Detroit cells (P/3-5) were cultured in EMEM (containing 10% FBS, 1 % Sodium Pyruvate, 1% L-Glutamine, 1 % Peniciline-Streptomycine) on bacterial cellulose membranes and 37 C, 5% CO 2. Expected Results: Mechanical strength of BC membranes with cultured Detroit cells and without cells will be compared by using a specifically designed and produced mechanical testing device. We expect an increase in mechanical strength of BC due to penetration of extracellular collagen produced by cells on the BC nano-fibrils. Cell viability, cell adhesion to cellulose and porous structure of cellulose will be evaluated by MTT analysis and SEM images. Acknowledgement I would like to thank Tuğçe DEMİR for her valuable comments and suggestions about my experimental studies.. Fig.1. Static incubation of culture and purified BC membrane [1]Klemm D, Schumann D, Udhardt U, Marsch S. Bacterial synthesized cellulose artificial blood vessels for microsurgery. Prog Polym Sci 2001;26: [2]Scionti.,G.,(2010),Mechanical Properties of Bacterial Cellulose Implants,Technical Report n.366 Dep. of Che. and Biological Eng., Biopolymer Technology, Chalmers Univ. of Technology [3]Hestrin S, Schramm M. Synthesis of cellulose by Acetobacter xylinum. Biochem J 1954;58:

87 P-BM17 Synthesis And Characterization Of Polyurethanes For Biomedical Applications Filiz Kara 1, Eda Ayşe Aksoy 2,3, Nesrin Hasırcı 3,4, Serpil Aksoy*,1 1 Gazi University, Department of Chemistry, Ankara, Turkey 2 Central Laboratory, Middle East Technical University, Ankara, Turkey 3 BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara, Turkey 4 Middle East Technical University, Department of Chemistry, Ankara, Turkey Keywords: biomaterial, polyurethane, synthesis Introduction: Polyurethanes (PUs) are one of the most biocompatible and hemocompatible class of materials which are widely used in biomedical applications such as coatings for electrical devices, catheters, arteries, scaffolds, etc. in different forms such as sponge, foam, fiber, film, tube etc. They are generally obtained by condensation reaction of diisocyanates and polyols forming domains of hard and soft segments. Presence of soft segment is contributed by polyols and provides elasticity, while isocyanates form hard segments and give the strength of the material. Type (aromatic or aliphatic isocyanates, polyester or polyether based polyol) and size of the components (molecular weight of polyols) and the production process control the mechanical and thermal properties of the final product. Methods: PU films were synthesized in medical purity by using excess toluene diisocyanate (TDI) or hexamethylene diisocyanate (HDI) and polypropylene ethylene glycol via one-shot polymerization without using any other ingredients such as catalyst, chain extender or solvent at 90 C and under vacuum [1,2]. TDI and HDI based PUs were coded as PUt and PUh, respectively. Chemical compositions of the prepared films were determined by solid state 13 C-NMR and FTIR-ATR; surface hydrophilicity and roughness were examined by goniometer and AFM; thermal and mechanical properties were evaluated by TGA, DSC and a mechanical testing machine, respectively. The effect of composition on the properties were examined. Results: All FTIR-ATR spectra of PUs showed characteristic PU bonds, N-H stretching vibration at 3300 cm -1 and carbonyl stretching vibration at 1720 cm -1. DSC results showed that Tg values were - 50 C for PUt and -58 C for PUh. These results indicated that extent of hard and sort segment phase mixing of TDI based films were better than that of HDI because of the segmental hexamethylene contribution. Mechanical properties such as elastic modulus, tensile strength, and elongation at break for PUt were 2.98 MPa, 1.95 MPa and 130%, respectively and for PUh 2.64 MPa, 0.72 MPa and 40%, respectively. PUt demonstrated higher tensile strength and modulus in comparison to PUh, most probably due to the aromatic structure of TDI which leads to high rigidity. Discussion & Conclusions: PU films were synthesized in medical purity without using any other ingredients such as catalyst, chain extender, or solvent. Results indicated that both TDI and HDI based PUs have elastomeric properties and aromatic diisocyanate compound improved mechanical properties. [1] N. Hasirci and E.A. Aksoy (2007). High Perform Polymer 19: 621 [2] E. A. Aksoy, N. Hasirci (2012) J Biomat. Tissue Eng. 2;

88 P-BS01 Design of an ultrasensitive impedimetric biosensor using anti-pth for quantification of parathyroid hormone Burçak Demirbakan 1, Burcu Özcan 1, Gülden Yeşiller 1, Münteha Nur Sonuç *,2, Mustafa Kemal Sezgintürk 1 1 Namik Kemal University Faculty of Science, Biochemistry, Tekirdağ Turkey 2 Namik Kemal University, School of Health Tekirdağ Turkey Keywords: cancer biomarker, impedimetric biosensor, PTH Introduction: The changes in secretion of parathyroid hormone should be recognized as causes of serious diseases such as hyperparathyroidism due to a parathyroid tumor which secretes PTH without regulation [1,2], or hypoparathyroidism which results in lowered levels of calcium[3]. Electrochemical impedance spectroscopy (EIS) is a powerful method to analyze interfacial properties of biosensor systems for significant biomarkers. We aimed to construct new biosensor system to detect this marker sensitively and selectively. Methods: A three-electrode system, consisting of a gold working electrode, a Ag/AgCl reference electrode and a Pt counter electrode were used. EIS and CV were applied to monitore binding events of biosensor. To obtain self assembled monolayers cysteine solution was used. For anti-pth immobilization, EDC was used as a heterobifunctional cross-linker. The performance of the biosensor was evaluated in terms of linearity, sensitivity, repeatability and reproducibility, after important optimization studies were carried out. Finally, the biosensor was applied to the artificial serum samples spiked with PTH. Results: Fig 1A and B show CV and EIS results of Au, Au/Cys, Au/Cys/Anti-PTH/, Au/Cys/Anti-PTH/BSA, and Au/Cys/Anti- PTH/BSA/PTH. Optimal Anti-PTH concentration and incubation period were found 5 ng/ L and 60 min. respectively. The increment of PTH concentration 72 increased the charge transfer resistance achieving a linear range between 10 and 60 fg/ml. The reproducibility of system was approved by using different biosensors that Fig 1A and 1B. CV and EIS of different layers of biosensor analysis for ten times. For the present anti-pth based biosensor, performing for Kramers-Kronig Transforms the real part of the experimental data was used to calculate the imaginary part of a linear, stable, and causal circuit. Discussion & Conclusions: We reported a simple electrochemical biosensor for detection of PTH with ultrahigh sensitivity. Anti-PTH antibody was firstly utilized in this study to detect PTH. PTH levels of the artificial serum samples analyzed by the present biosensor were agreed with that of the spiked amount of it to the artificial serum samples. Acknowledgements: Scientific and Technological Research Council of Turkey (TÜBİTAK, Project number: 109 T 172). : [1] S.Yano, T. Sugimoto, T. Tsukamoto, et al. (2000) Kidney Int 58 [2] S. Cañadillas, A. Canalejo, R. Santamaría, et al (2005) J. Am. Soc. Nephrol 16:2190 [3] J.P. Bilezikian, A. Khan, J.T. Potts (2011) J. Bone Miner. Res. 26:

89 P-BS02 Electrochemical impedance spectroscopy based biosensor for the detection of cytochrome c Hüsniye Kahraman 1, Ayten Gizem Özbek 1,Çağrı Altuğ *,1 Umut Mengüllüoğlu 1, Erhan Dinçkaya 1 1 Ege University Faculty of Science Department of Biochemistry İzmir, Turkey Keywords: Affinity, apoptosis, biosensor, cytochrome c, EIS Introduction: Biosensors are an analytical devices, used for the detection of an analyte that combines a biological component with a physicochemical detector [1]. Cytochrome c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It is a component of the electron transport chain in mitochondria. Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. Cytochrome c release from the mitochondria is a sentinel signal initiating apoptosis and serum levels of cyt-c have been used as a marker of apoptosis. Methods: The aim of this work is to develop biosensor technology for determination of cytochrome c in blood serum quickly, practically and accurately. In this scope, it is planned to develop the biosensors utilizing electrochemical impedance spectroscopy (EIS) for analyzing of the compounds that has a restricted catalytic interaction activity such as cytochrome c. In recent years, EIS becomes a power tool for examining many chemical and physical processes. Conversely, of enzyme-substrate interactions, biomolecule interactions which have no reaction sequence after binding like antigen-antibody, DNA etc, charge transfer changes occurred after affinity interactions can also be monitored by the help of EIS. In the presented project, development of the biosensor technologies based on electrochemical impedance spectroscopy using specific antibodies to cytochrome c and the analyses of cytochrome c by the developed biosensor technologies are conceived. Results: In this work here described it was developed a biosensor which is based electrochemical impedance spectroscopy. This affinity based biosensor was constructed colloidal gold and anticytochrome c antibody which specific bind with cytochrome c. We developed the electrode and optimized the measurement conditions. Optimization studies of the immobilized anti-cytochrome c antibody electrode were executed. Optimum specific bind time was detected 30 minutes, optimum temperature was established 350C and optimum stirring velocity was detected as 100 rpm. Discussion & Conclusions: Description of conclusions, recommendations, and limitations based on findings. Acknowledgements: This work was supported by TÜBİTAK (The Scientific and Technical Research Council of Turkey) Project Number: SUPPORT PROGRAM OF NATIONAL /ABROAD UNDERGRADUADE RESEARCH PROJECTS UNDERGRADUADE [1] Turner, Anthony; Wilson, George and Kaube, Isao (1987). Biosensors:Fundamentals and Applications. Oxford, UK: Oxford University Press. p [2] Tafani M, Karpinich NO, Hurster KA, Pastorino JG, Schneider T, Russo MA, Farber JL (March 2002). J. Biol. Chem. 277 (12): [3] Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2008). Molecular Biology of the Cell (textbook) (5th ed.). Garland Science. p

90 P-BS03 Storage stability of electrochemical DNA biosensors Filiz Kuralay 1,2, Susana Campuzano 1,3, Joseph Wang*,1 1 Department of Nanoengineering, University of California San Diego, La Jolla, CA, United States 2 Department of Chemistry, University of Ordu, Ordu, Turkey 3 Department of Analytical Chemistry, Universidad Complutense de Madrid, Madrid, Spain Keywords: Dithiols, DNA, Storage Stability Introduction: In this work ternary thiolated monolayers impart dramatic improvement in the storage stability of DNA electrochemical biosensors. Highly stable interfaces are prepared by co-immobilizing the thiolated capture probe (SHCP) with 1,6-hexanedithiol (HDT) on gold substrates, followed by the incorporation of 6- mercaptohexanol (MCH) diluent. The resulting DNA recognizition platform (SHCP/HDT+MCH) offers higher storage stability compared to conventional monolayers (SHCP/MCH). Methods: For the preparation of SHCP/HDT+MCH, a mixture of SHCP and freshly prepared HDT, with appropriate concentrations, was prepared and allowed to stand for 10 min. Aliquots of 6 L of this mixture were cast over each electrodes and incubate overnight. After washing with water and drying with nitrogen, the mixed monolayer-modified Au sensors were subsequently treated with 6 L of a MCH solution. Results: The prolonged stability of the ternary DNA recognition platform was compared with that of conventional monolayer [1]. An extended period of 3 months was employed to examine and compare the long term-stability of both interfaces in dry conditions. To examine the role of the linear dithiol compound, HDT, the performance and the prolonged stability of the SHCP/HDT was also assessed. Fig. 1 shows the schematic presentation of the monolayer-modified Au sensors. Fig. 1. Schematic presentation of the monolayer-modified Au sensors. Discussion & Conclusions: The enhanced stability may lead to improved stability of DNA biosensors based on other transduction modes that rely on selfassembled monolayers. Acknowledgements: Financial support from the National Institutes of health (Award U01 AI075565) is gratefully acknowledged. [1] F. Kuralay, S. Campuzano, J. Wang. (2012). Talanta 99:

91 P-BS04 Electrochemical determination of homocysteine at disposable graphite electrodes Ece Eksin 1, Arzum Erdem*,1 Ege University, Faculty of Pharmacy, Analytical Chemistry Department, Bornova, Izmir Turkey Keywords: Amino acids, Electrochemistry, Homocysteine, Pencil graphite electrode. Homocysteine (Hcy) is an endogenous sulfhydryl amino acid (shown in Fig. 1), which is generated by the demethylation of methionine. Once formed, Hcy is either irreversibly catabolized by transsulfuration to cysteine or remethylated to methionine (Met). These transformations are controlled by enzymatic reactions [1,2]. Fig. 1. The chemical structure of Homocysteine (Hcy) The plasma homocysteine level is regulated and the normal basal concentration ranks from 5 to 15 µm with a mean level of about 10 µm [1]. For upper Hcy levels, hyperhomocysteinemia is described. Every 3 µm plasma increase at the Hcy level contributes to a 10 % increased risk of stroke. Additionally, in the case of high blood level of Hcy causes particularly cancer, dementia and Parkinson s disease [3]. Because of its high importance, the determination of Hcy levels in biological fluids has recently received a great attention. The analysis of Hcy has been performed by using various methods; capillary electrophoresis [4], gas chromatography [5], fluorescence [6] mass spectroscopy [7] and high performance liquid chromatgraphy [8-10]. These methods are mostly time consuming by requiring expensive chemicals and expensive equipments for electrochemical monitoring of Hcy. Therefore, it is aimed in our study to develop a novel, simple, sensitive and selective detection method for Hcy using a singleuse pencil graphite electrode (PGE) in combination with differential pulse voltammetry (DPV) technique. Compared to the results obtained by traditional methods in literature, more sensitive Hcy analysis was performed herein using more practical and cost-effective protocol by using DPV and PGE technology. Acknowledgements: A.E. acknowledges the financial support from the Turkish Scientific and Technological Council (TUBITAK, Project No. 212T082) and Ege University Science and Technology Research and Application Center (EBILTEM) Project No. 2013/BIL/006). E.E acknowledges a master project scholarship through by TUBITAK (TUBITAK, Project No. 212T082). : [1]V. Ducros, K. Demuth, M.P. Sauvant, M. Quillard, E. Causse, M. Candito, M.H. Read, J. Drai, I. (2002) J. Chrom. B 781: [2] S.E.S. Miner, J. Evrovski, D.E.C. Cole. (1997). Clin. Biochem. 30: [3]S.T. Koz, N. T. Gouwy, N. Demir, V. S. Nedzvetsky, E. Etem, G. Baydas. (2010). Int. J. Devl. Neurosci. 28: [4]N. Maeso, D. G. Martinez, F.J. Ruperez, A. Cifuentes, C. Barbas. (2005). J. Chromatogr. B 822: [5]Y. Shinohara, H. Hasegava, K. Tagoku, T. Hashimoto. (2001). J. Chromatogr. B 758: [6]Y. Mukai, T. Togawa, T. Suzuki, K. Ohata, S. Tanabe. (2002). J. Chromatogr. B 767: [7] K. Tuschl, O.A. Bodamer, W. Erwa, A. Mühl. (2005). Clin. Chim. Acta. 351: [8] A. Khan, M.I. Khan, Z. Iqbal, Y. Shah, L. Ahmad, S. Nazir, D.G. Watson, J.A. Ahan, F. Nasir, A. Khan A., Ismail. (2011). Talanta 84: [9] J. Deramo, A.E. Finkelstein, F.O. Boccazzi, O. Fridman. (1998). J. Chromatogr. B 720: [10] L. Agui, C. Pena-Farfal, P. Yanez-Sedno, J.M. Pingarron. (2007). Talanta 74:

92 P-BS05 Electrochemical investigation of Topotecan-DNA interaction by using carbon nanotubes modified pencil graphite electrodes Gulsah Congur 1, Fehmi Mese 1 and Arzum Erdem *,1 Ege University, Faculty of Pharmacy, Analytical Chemistry Department, Bornova, Izmir, Turkey Keywords : Carbon nanotubes, drug-dna interaction, electrochemical DNA biosensor, Topotecan Topotecan (TPT, shown in Fig. 1) is a semi synthetic analog of the plant alkaloid camptothecin and known with commercial name, Hymcantin. It has been widely used as topoisomerase I inhibitor for the purpose of treatment of ovarian and cervical cancers [1,2]. TPT induces DNA lesions via the formation of stable cleavable complexes of topoisomerase I and DNA in vitro and in vivo [3]. Fig. 1. The molecular structure of Topotecan. There have been numereous studies in literature for the detection of TPT, by using conventional techniques; such as HPLC [4], LC MS [5] and fluorescence [6]. Electrochemical (bio)sensing techniques [7-9] can provide more sensitive, cost effective and selective detection protocols for drug, DNA and protein monitoring including their interactions in comparison to other techniques. In the present study, disposable pencil graphite electrodes (PGE) were firstly modified with single walled carbon nanotubes (SWCNT). The SWCNT-PGEs were tested for voltammetric detection of TPT and DNA compared to unmodified electrodes, and consequently, the enhanced oxidation signals for TPT and DNA were recorded using SWCNT-PGEs by using differential pulse voltammetry (DPV) technique. The changes at the oxidation signals of TPT and guanine were examined in order to understand the interaction process. Acknowledgements: A.E would like to express her gratitude to the Turkish Academy of Sciences (TUBA) as an Associate member for its partial support. G.C. and F.M. acknowledge a master project scholarship through by project (TUBITAK Project no.111t073). [1] J.V. Fiorica (2003) Gynecol. Oncol. 90: S16. [2] D. Lorusso, A. Pietragalla, S. Mainenti, V. Masciullo, G. Di Vagno, G. Scambi (2010) Crit. Rev. Oncol.Hematol. 74:163. [3] D. Subramanian, E. Kraut, A. Staubus, D.C. Young, M.T. Muller (1995) Cancer Res. 55:2097. [4] H. Rosing, E. Doyle, B.E. Davies, J.H. Beijnen (1995) J. Chromatogr. B 668:107. [5] C. Arellano, P. Gandia, L. Bettuing, J. Woodley, E. Chatelut (2010) J. Chromatogr. B 878:645. [6] T.G. Burke, H. Malak, I. Gryczynski, Z. Mi, J.R. Lakowicz (1996) Anal. Biochem. 242:266. [7] Erdem, Chapter 19: Genosensor technology for electrochemical sensing of nucleic acids by using different transducers, Comprehensive Analytical Chemistry, Electrochemical Sensor Analysis, Ed. S. Alegret and A. Merkoci, vol. 49, Elsevier, (2007), pp [8] Erdem, M. Ozsoz (2002) Electroanalysis 14: 965. [9] E. Palecek, M. Fojta (2007) Talanta 74:

93 P-RM01 Three Dimensional Cross-linked Collagen Skin Equivalent Model Begüm Zeybek 1, Cemile Kılıç 3,5,6, A. Şendemir Ürkmez 1,2, Nesrin Hasırcı 4,5,6, Vasıf Hasırcı 3,5,6* 1 Ege University, Department of Material Sciences and Engineering 1, Bioengineering 2, Izmir, Turkey METU, Departments of 3 Biological Sciences, 4 Chemistry, and 5 Biotechnology, Ankara, Turkey 6 BIOMATEN, METU CoE in Biomaterials and Tissue Engineering, Ankara, Turkey * Keywords: Collagen, cross-linking, porosity, scaffold, skin Introduction: Skin is the largest organ in the human body and serves as a barrier between the human body and environment. In the past 30 years, great efforts have been spent in order to develop substitutes which can mimic human skin [1, 2]. In this study construction of a bilayer tissue engineered skin substitute is aimed. This substitute is planned to be constituted of collagen and natural polysaccharides to fulfill the hydration, microbial and physical barrier, moisture controlling requirements of a natural skin. Methods: Scaffolds were prepared by freezedrying, and crosslinked either physically or chemically. The required collagen porosity was achieved by controlling the production parameters such as concentration, freezing temperature, crosslinking, and material composition. Results: The stability of the collagen foams prepared by lyophilization was tested in PBS at 37 o C (Figure 1). While uncrosslinked foams lost all their weight within 3 days, the physically crosslinked (DHT) and chemically crosslinked (glutaraldehyde) foams retained 80% of their weight indicating that the crosslinked forms of the foams are needed for in vitro studies. This was also checked by compression testing of the foams and while the Young's modulus and the compressive strength of the uncrosslinked foams were 5.28 and kpa, respectively, upon crosslinking they were significantly increased to and kpa, respectively, showing an increased mechanical strength due to crosslinking. Weigth Remained (%) In situ degradation of foams in PBS Time (Days) Fig. 1. The increased stability of the foams upon crosslinking with physical (DHT) and chemical (Glu) means. Fig 2. Collagen foam SEM image Discussion & Conclusions: With all predefined properties, the skin is expected to allow cell ingrowth and proliferation and angiogenesis. The characterization studies (porosity, pore size distribution, SEM) are in progress (Figure 2) and will be followed by the in vitro studies involving a co-culture system. [1] MacNeil, S. (2007) Nature 445(7130): [2] Bottcher-Haberzeth, S., T. Biedermann. (2010). Burns 36(4): DHT DHT + V UXL 77

94 P-RM03 Evaluation of decellularized bovine cardiac tissue for cell culture and as a guiding template Hatice Ercan 1,2, A. Eser Elçin 1,2, Y. Murat Elçin *,1,2 1 Ankara University Stem Cell Institute, and 2 Ankara University Faculty of Science, Ankara 06100, Turkey Keywords : Cardiac tissue engineering, Decellularization, Extracellular matrix Introduction: The cause of most cardiovascular diseases is the decrease in both number and regenerative capacity of cardiomyocytes over time. Cardiac tissue engineering aims to repair, regenerate or replace damaged tissue, by creating functional tissue constructs that can repair cardiac tissue through vascularization or cell recruitment [1]. Scaffolds have been instrumental in promoting cell adhesion, growth, proliferation, and in providing a mechanical and instructive support. Decellularization offers a naturally derived biomaterial that provides several advantages such as biodegradability, biocompatibility, and remodeling, compared to synthetic biomaterials [2]. Here, we have evaluated the efficiency of decellularized bovine cardiac extracellular matrix (bc-ecm) as a natural scaffold for mesenchymal stem cell (MSC) culture and differentiation. Methods: In this study, bovine heart tissue was decellularized to obtain an acellular scaffold using a protocol that involves successive physical treatments (freezing/thawing), acid (peracetic acid) and detergent treatments (SDS), lyophilization and sterilization [3]. DNA content analyses were carried out to determine cellular remnants. SEM and histological analyses were performed to evaluate decellularization. Bone marrow mesenchymal stem cells (rbm-mscs) were isolated from the bone marrows of Wistar rats using standard technique. rbm-mscs (between P2-P5) were seeded onto decellularized bc-ecm scaffolds. MTT assay was performed to assess MSC viability and proliferation on decellularized scaffold. Differential scanning calorimetry (DSC) was performed to evaluate the thermal properties of native and decellularized tissue [4-5]. Results: SEM images showed that bc-ecm scaffold had a porous morphology allowing cells to attach and proliferate within the decellularized structure. DNA content analyses results showed a significant decrease in the DNA level in decellularized bc-ecm when compared to the native bc-ecm. Acellularity was also confirmed by histological analyses. MTT assay demonstrated that rbm-mscs could attach and proliferate on decellularized bc-ecm scaffolds. According to the DSC thermograms, no significant difference in the thermal properties of native and decellularized tissues was observed. Discussion & Conclusions: Findings demonstrated that decellularized bc-ecm scaffolds supported cell attachment and growth, and could be considered as a suitable regenerative environment during cardiac repair. Future work is planned to evaluate this potential. Acknowledgements: Ankara University Stem Cell Institute (Ankara, Turkey); Turkish Academy of Sciences (TÜBA; to YME). [[1] Chiu, L.LY., Radisic M Current Opinion in Chemical Engineering 2: [2] Novakovic, G. V., Tandon, N. At et al Tissue Engineering 16: [3] Gilbert, T.W., Sellaro T.L., Badylak S.F Biomaterials 27: [4] Samouillan, V., Delaunay, F. et al Journal of Functional Biomaterials 2: [5] Zhang, Y., Luo, H. et al Biomaterials 31:

95 P-RM04 Comparison of in vitro Three-Dimensional (3D) Microtissue Forming Potential of Different Cell Types for Regenerative Medicine Applications Şükrü Öztürk 1, Mehmet Özgun Özen 2, Müjde Kıvanç 3, H. Seda Vatansever 4, Aylin Şendemir Ürkmez 5* 1 Biomedical Technologies Division, Ege University, Izmir-Turkey 2,5 Bioengineering Department, Ege Üniversity, Izmir-Turkey 3,5 Histology-Embryology Division, Faculty of Medicine, Celal Bayar University, Manisa-Turkey Keywords: Microtissue, non-adhesive agar gel, regenerative medicine, three-dimesional culture Introduction: According to basic biology, cells come together to form tissues in vivo. For tissue formation in the body, cell-cell and cellextracellular matrix (ECM) interactions are very important [1]. Tissue engineers must use techniques which provide these interactions to mimic in vivo structure [2]. One of the most important methods that provide cell-cell and cell- ECM interactions is creation of microtissues using non-adhesive surfaces [3]. In this study we used 3D non-adhesive agar gels technique to compare the microtissue forming potential of different cell types for regenerative medicine applications. Methods: Non-adhesive agar gels were produced using 3D Petri Dish TM molds, and mouse fibroblasts cell line (3T3), human epithelial keratinocyte (HS2) rat bone marrow stem cells (BMSC), rat adipose mesenchymal stem cells (AdMSC), human breast cancer cell line (MCF-7), human osteosarcoma cell line (SaOS-2) and human neuroblastoma cell line (IMR-32) were cultured in these 3D agar gels. Hematoxyline & Eosin (H&E) staining and (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay were performed to determine cell presence and viability in microtissue structure. To calculate the mean diameter of microtissues, Image Processing and Analysis in Java (ImageJ) was used. Results: Our results showed that, while 3T3, AdMSC, MCF-7, SaOS-2 and IMR-32 cells could form microtissues, HS2 and BMSC could not. H&E staining showed that 3T3, SaOS-2, IMR-32 and AdMSC microtissues produced ECM and MTT showed that cell numbers increased in IMR-32 and AdMSC microtissues after 16 days. Image processing results indicated that, in time the diameter of SaOS-2 and IMR-32 microtissues increased significantly (156% for IMR-32 microtissues, 125% for SaOS-2 microtissues). Discussion & Conclusions: According to all of these results we concluded that, while the cells which created 3T3, MCF-7, AdMSC, SaOs-2 and IMR-32 microtissues could interact with each other spontaneously in a non-adhesive environment, HS2 and BMSC need additional factors such as growth factors, co-culturing with other cells like fibroblasts, etc. to form 3D microtissues mimicking in vivo for regenerative medicine applications. In addition, microtissue formation ability of cancer cell lines can be a good tool for drug screening or theranostic tests instead of 2D culture techniques. Acknowledgements: We thank the all members of Ege Research Group of Animal Cell Culture and Tissue Engineering (EgeREACT) for helpful thoughts and suggestions. [1] Rago P.A., Dean M.D., Morgan R.J., (2008), Biotecnology and Bioengineering: 102, [2] Kelm M. J., Fussenegger M., (2004). TRENDS in Biotechnology: 22: [3] Napolitano P.A., Chai P., Dean M.D., Morgan R.J. (2007). Tissue Engineering, 3:

96 P-RM05 Design of various hydrogels for 3D bioprinting method and investigation of cell viability Şeyma Bektaş 1, S. İsmet Deliloğlu Gürhan 1, Aylin Şendemir Ürkmez 1* 1 Ege University, Department of Bioengineering, Izmir, Turkey * Keywords: 3D bioprinting, alginate, chitosan, hydrogel, tissue engineering Introduction: 3D bioprinting is a new tissue engineering approach, where a homogeneous distribution and controlled positioning of cells in the scaffold is achieved. Hydrogels are used for carrying and mechanical protection of cells, while providing them opportunity to move and allowing the diffusion of oxygen and nutrients to keep the cells alive during the process[1]. In this study, chitosan, alginate and chitosan /alginate hydrogels are designed for 3D bioprinting. Methods: Alginate and chitosan was used to make 1%, 2%, 3%, chitosan and chitosan/alginate hydrogels for bioprinting purposes. Glycerol-2- phosphate disodium (GP) salt and Ca +2 ions were used to achieve physical cross-linking, and to slow down the rate of degredation. Degradation rate of hydrogels was determined spectrophotometrically. Direct contact cytotoxicity tests were applied on B35 rat central nervous system cell line, and the survival of cells was investigated by MTT test. Results: Microscopy images show that cells were maintained alive during the prosess (Fig 1). Cytotoxicity results conformed these data. It's thought that porosity of the hydrogel allow cell migration. FTIR spectra a peak at 1640 nm shows that bonding is comprised between chitosan and alginate. GP salt increased ph value of chitosan to neutral ph. This case is a key factor for both biocompatibility and homogenization of chitosanalginate hydrogels. Ca +2 ions achieved physical cross-linking, and slowed down the degradation of the hydrogel. Fig. 1. Microscope imagine of alginate/chitosan hydrogel Discussion & Conclusions: Chitosan/alginate hydrogels behaved as ECM-like, 3D reticulated structures that are able to support volumetric and mechanical protection to the cells, allowing the diffusion of oxygen and nutrients to keep the cells alive, while providing opportunities for the cells to move and maintain their cell-cell interactions. Also cross-linking has increased the mechanical strength of the hydrogels. Acknowledgements: This work was partially supported by TUBITAK (The Scientific and Technological Research Council of Turkiye) by undergraduate research support program. [1] Jakab, K., Norotte, C., Marga, F., Murphy, K., Vunjak- Novakovic, G., Forgacs, G., Biofabrication, 2(2010)22001:

97 P-TM01 Developing a Three-dimensional (3D) Cancer Tissue Model with Tissue Engineering Approach Müge Anıl 1, Aylin Şendemir Ürkmez 1, Gülperi Öktem 2 and S. İsmet Deliloğlu Gürhan*,1 1 Department of Bioengineering, Faculty of Engineering, Ege University, Bornova- Izmir, underlined) Turkey 2 Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova-Izmir, Turkey * Keywords: Breast cancer, cancer stem cell, three-dimensional cell culture, tissue scaffold Introduction: Traditional two-dimensional (2D) cell culture system was a convenient way to study cancer cells in vitro, but, 2D cell culture systems have serious limitations. 2D model is not successful to mimic the tumor niche such as cell-cell communications and cell-extracellular matrix (ECM) interactions, which play a key role in cancer tissue [1]. The three-dimensional (3D) cell culture system in vitro is closely related to tumorigenicity in vivo and the gap between 2D system and tumors in vivo can be bridged by a succesful 3D cell culture system. 3D scaffolds might provide a useful platform for research on anti-cancer therapeutics, theranostics and cancer stem cells (CSCs). Methods: In this study, breast cancer stem cells (BCSCs) were isolated from breast cancer cell line MCF 7. BCSCs which are CD44 (+) CD24 (-/low) cell population, were isolated by catcher-tube based cell sorter on flow cytometer machine. BCSCs and cancer cell population without CSCs were observed as in vitro spheres by using liquid overlay technique and colony formation efficiencies of these cells were investigated comparatively with MCF 7 cell line. As the 3D model, chitosan scaffold which is produced with lyophilization technique was used. Some scaffolds were coated with gelatin for enhancing cell adhesion. The morphologies of both CD44 (+) and CD44 (-) cells were also examined by scanning electron microscopy (SEM). Fig. 1. BCSCs on gelatin coated chitosan scaffold. Results: The results indicated that the CD44(+) CD24(-/low) cell population were capable of proliferation as adherent cells on chitosan and gelatin coated chitosan scaffolds. On scaffolds, cell spheres were morphologically similar to tumor tissue (Fig 1). Discussion & Conclusions: This study is seen as an introduction to develop a novel 3D scaffold model to study cancer stem cell behaviour and tumorigenesis in vitro. Developing a 3D tumor model which is originated from CSCs might be a fast and economical alternative to animal experimentation to study behavior of BCSCs and develop strategies for cancer treatment. Acknowledgements: This work was supported by Ege University Science and Technology Center (EBILTEM). [1] Kim, J.B. (2005). Seminars in Cancer Biology 15: [2] Verbridge, S.S., Chandler, E.M. and Fischbach, C. (2010) Tissue Engineering: Part A 16:

98 P-TM02 Hope of proton and hadron therapy in cancer treatment Esma Uzunhisarcıklı 1, Hatice Erkekoğlu 1, Seval Bülbül *,1 1 T.C. Erciyes University, Kayseri, Turkey Keywords: cancer, cancer patients,economy,health tourism,proton therapy Introduction: Cancer is one of the most important and dangerous diseases of our age. It is a disease which has the second highest mortality level coming after cardiovascular diseases in Turkey [1]. The facts that the disease may occur in different parts of the body or there is not a disease or symptom specific to tissue, the disease has a heavy material and moral burden, the diagnosis and treatment period of time of the disease take a long time and high number of mortality related to the disease necessitate leading and turning faces of professionals towards cancer researches and to take measures about this issue [2]. Methods: The facts that the disease may occur in different parts of the body or there is not a disease or symptom specific to tissue, the disease has a heavy material and moral burden, the diagnosis and treatment period of time of the disease take a long time and high number of mortality related to the disease necessitate leading and turning faces of professionals towards cancer researches and to take measures about this issue. Results : Even if setup costs and the greatness of the required area for establishing hadron and proton therapy centers are seen as a disadvantage, it's set forth that such therapy provides greater advantage than other methods by succeeding in diagnosis and treatment of many cancer types, determining the ranges of cancerous cells clearer than other imaging systems and minimizing the risk of being exposed to harmful rays for other organs thanks to its high focusing function. Discussion & Conclusions: There is no hadron therapy center in Turkey, yet. Developed countries use this method today and increase the number of their centers day by day. Establishing such therapy centers is important for Turkey to keep up with the developed countries in health issue. A hadron and proton therapy center in Turkey will be a source of hope for cancer patients as well as provide citizens of neighboring countries to visit our country for using this method. Thus, it will contribute to national economy in terms of health tourism. [1] [2]Kutluk Tezer, Kars Ayşe. (2001) Türk Kanser Araştırma Ve Savaş Kurumu, Ankara. 82

99 P-TM03 Effect of in vitro Mechanical Tension on Central Nervous System Neurons O. Mert Duman 1, Mehmet Sarıkanat 2,3, Aylin Şendemir Ürkmez 1,3* 1 Ege University, Departments of Bioengineering, Mechanical Engineering 2,3, Biomedical Technologies 1,3*, Turkey Keywords: PCL, CNS, PC12, electrospinning Introduction: Central nervous system damage has become one of the important health problems in developed countries because of the increasing life expectancy. Effects of mechanical loading on development of central nervous system (CNS) cells and neurite extension have been recognized recently. Effects of loading are very complicated since until a threshold, tension plays a positive role while after the threshold value, it is degenerative. There are some mechanical trauma models in the literature, but they usually employ hard and two dimensional culture substrates, which fail to mimic the natural niche of the cells. The aim of this project is to create an in vitro experimental model that can mimic the physiological habitat and normal loading conditions on CNS cells. Methods: 12% polycaprolactone (wt/v) is dissolved in 1:1 dimethylformamide and dichloromethane. Solution is produced as a nanofibrous scaffold by electrospinning. Cells are cultivated in RPMI1640 medium with 5% fetal bovine serum (FBS), 4ng/ml basic fibroblast growth factor (bfgf), 100 U/ml penicillin and 100 mg/ml streptomycin. Cell culture is incubated at 5% CO 2 and 37 C. The mechanical straining device consists of a moving upper part and stable base part. Nanofibrous tissue engineering scaffolds are fastened to the bottom of the upper cylinder and fixed with the grooves. By this set-up, a uniform, bi-axial strain is applied on attached cells. The displacement and frequency are computer controlled, and all experiments are carried out in a reservoir under sterile conditions. Figure 1: Tension application Results: Effects of different levels of mechanical strain on cell morphology, neurite elongation and cytoskeleton are under investigation. The strain threshold level for PC12 cells that the degenerative effects start and the apoptosis pathways will be determined. Discussion & Conclusions: Neuron growth and neurite elongation for the tissue engineering studies can be supported by this bi-axial straining technique. By this model, a powerful system is built to simulate traumatic brain injury due to falls, traffic accidents and battlefield explosions, etc. This model will also allow experimentation with new drugs and treatments in vitro. By increasing the variables, like co-culturing relevant cell types, modifying mechanical loading conditions, etc., trauma models closer to in vivo conditions can be generated. Acknowledgements: This work is funded by The Scientific and Technological Research Council of Turkey (TUBITAK) (111M605). [1]Chetta J et al, Cytoskeleton 2010;67(10): [2]Hengst U et al, Nature Cell Biology 2009;11(8): 1024-U

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