Tailored bioabsorbable implants and scaffolds for biomedical and tissue engineering applications

Tailored bioabsorbable implants and scaffolds for biomedical and tissue engineering applications Minna Kellomäki Professor, Dr Tech, FBSE BioMediTech and Department of Electronics and Communications Engineering Tampere University of Technology, Finland

Tekes review 289/2012, p. 63 History of biomaterials research in Finland

4.9.2013 1 st in the world innovations and products 1st in the world several surgical implant families introduced to clinical studies, examples: Ultra-high strength pins and screws for bone fracture fixation Membranes for guided tissue regeneration Arrows for closing of knee meniscus ruptures Stents for urological and gastro-enterological applications Malleable plates for craniomaxillofacial, spine and thoracic surgical applications Antibiotic releasing screws for prophylactic applications Bioreconstructive scaffolds for finger and toe joint regeneration 3

Biomaterials research areas Leader: Minna Kellomäki Prof, Dr Tech, FBSE Processing, microstructures and properties of: Bioabsorbable, synthetic polymers Hydrogels Modified natural organic materials Polymer-ceramic composites Bioceramics and bioactive glasses Development of: Surgical implants and implantable measuring devices Scaffolds for tissue engineering Drug releasing biomaterials Biocompatible surfaces and electrical properties of biomaterials

Advanced Tissue Regeneration Technology; Osteopromotive Composite Scaffolds and Cellular Response with Human Adipose Stem Cells KURKO

Requirements for TE-scaffold technology Requirements for a tissue engineering scaffold: Biocompatible Optimal pore size Interconnected pore structure Bioabsorbable Requirements for a technology transfer from the lab to the clinics: Better functionality or activity compared to the existing technology High manufacturing rate and yield Low manufacturing costs Easy to use

Scaffold structures PLCL: Porosity up to 70 % Average pore size 500-1000 µm Max pore size 1300-2300 µm PLCL-β-TCP 40 wt-%: Porosity up to 70 % Average pore size 300-800 µm Max pore size 600-2300 µm Scaffold + water PLCL-β-TCP 60 wt-%: Porosity up to 60 % Average pore size 300-600 µm Max pore size 600-1500 µm Scaffold phase Water phase Pore interconnectivity 98-99 %

In vitro cytocompatibility Seeding with human adipose stem cells (660 cells/ mm 3 ) Cell attachment and viability Live/dead-fluorescent probes Cell proliferation Quantitative DNA analysis (CyQuant) Early stage osteogenic differentiation Quantitative alkaline phosphatase activity Adipose stem cells have been used successfully for clinical bone regeneration [2,3] [2] Mesimaki K, et al. Int J Oral Maxillofac Surg, 2009. [3] Thesleff T, et al. Neurosurgery, 2011.

Conclusions ScCO 2 -processing enables effective manufacturing of porous and biodegradable scaffolds without harmful solvents The scaffolds mechanical properties enable cyclic loading and easy tailoring of the scaffolds to the desired shape PLCL 70/30 β-tcp scaffolds support the attachment and stimulate the proliferation of hascs Preliminary results show also that the scaffolds induce the early osteogenic differentiation

The Team and Acknowledgements Scientific team: Tampere University of Technology Professor Minna Kellomäki Kaarlo Paakinaho Niina Ahola Professor Mika Valden Leena Vuori Professor Jari Hyttinen Markus Hannula Tampere University Doc. Susanna Miettinen Suvi Haimi Laura Tirkkonen Sanna Huttunen Funding and collaboration: The Finnish Funding Agency for Technology and Innovation Industrial collaboration: Aalto University Professor Jukka Seppälä Laura Elomaa International collaboration with: Professor Dirk Grijpma, University of Twente, The Netherlands Professor Marcy Zenobi-Wong, ETH Zürich, Switzerland Professor Maria Rita Passos-Bueno, University of Sao Paulo, Brazil

Biomaterials for regenerative medicine - Human Spare Parts project http://www.biomeditech.fi/research/human_spare_parts_program.php

In the picture 1990 s human spare parts Scientific teams: Tampere University of Technology Professor Minna Kellomäki (Biomaterials) Professor Jari Hyttinen (Imaging and image analysis) Ptofessor Jukka Lekkala (Biosensors and measurements) Professor Pasi Kallio (Biomimetic environments) Tampere University Doc. Susanna Miettinen (Adipose stem cells) Doc. Susanna Narkilahti (Neuro) Doc. Heli Skottman (Ophthalmology) Doc. Katriina Aalto-Setälä (Cardiac cells and tissues) Main funding: The Finnish Funding Agency for Technology and Innovation http://www.biomeditech.fi/research/human_ spare_parts_program.php

Biomaterials research themes in HSP 1. Fibers and 2D & 3D textiles 2. Hydrogels and functionalization of materials 3. Biodegradable sensors Application areas: 1. Regenerative medicine 2. Cell culture surfaces and devices 3. Material development and characterization 13 4.9.2013

Melt-spun biodegradable fibers 4.9.2013 Melt processing of biodegradable polymers tools - Design and manufacturing of the equipment and - Optimization of parameters for spinning of fibers Coarse Fine Ultra fine Nano & Hollow fibers > 100 µm 100-30 µm 30-1 µm < 1 µm > 60 µm Slide by Ville Ellä / TUT BME

From fibers different textile structures 4.9.2013 From fibers production of multiple textile structures from textiles scaffolds and implants e.g. Knits Braids Non-wovens Wovens Slide by Ville Ellä / TUT BME

PLA96 + fibrin hybrids 16 Tschoeke B et al. Tissue Engineering 2009 Koch et al, Biomaterials 2010

Two photon polymerization 4.9.2013 - structures and functionalization - (additional partner: VTT) (a) (b) (c) Neurocages (2PP) Protein structures: BSA (left) and avidin (right) (2PP) Designed scaffold; close-up of nanostructure; cultured ASCs(2PP) Miniaturized 17 trabecular bone replica (2PP)

Shift of Frequency (MHz) Embedded measuring circuits - Measuring circuit embedded inside polymer foils - Distant reader system - Detection of water diffusion into the polymer structure - We can use this information to e.g. - Understand material behavior more deeply - Enhance material selection process for applications - By improving models how polymers degrade (collaboration prof Pan, Univ Leicester) 0-0.5-1 Salpavaara et al, 2012 PCL 2,40 mm PLCL 2,09 mm PDMS 2.19 mm -1.5 0 20 40 60 80

Biomaterial requests in HSP 4.9.2013 Permanent > temporary Biostabile bioabsorbable > bioactive Replacement - repair > tissue engineering Solid -> porous Hard/rigid & soft/flexible & hydrogel/gel 2D & 3D Macro & micro & nano Basic research > R&D > commercialization/products 19