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1 In vivo Micro CT Evaluation of From Bioresorbable Material to Sensor Applications biodegradable Magnesium in Medical Technology Annelie-Martina Weinberg, Mathias-Spital Rheine Germany / TU Graz - Austria Implants BRIC - Bioresorbable Implants for Children 1
2 Medicine sensor technology Contact leses - Blood glucose 2
3 Medicine sensor technology Chronical disease acute disease/injury Online monitoring Patient individulized medicine Reducing resources Faster reintegration in normal life 3
4 For example: Fracture treatment Healing dynamic process Implants are to rigid Changes in healing are not defined Biomechanical changes during healing unclear Total hip arthroplasty no knowledge about patient individual biomechnical properties 4
5 For example: brain damage Healing dynamic process Online information in the area of injured brain Stimulation during healing Observing the function of new cells 5
6 For example: miniaturism brain damage Miniaturism perfect body with no artificial parts 6
7 Conventional materials Stain Titanium and its alloys Cobald-chrome alloys 7
8 Biodegradable materials Appropriate materials: Metals: Mg, Fe Ceramics Polymers: Polylactide acide (PLA), Poly(3hydroxybutyrate) (PHB) Prerequisite for biocompatibility: bone cell adhesion to implant surface 8
9 Drawbacks of conventional materials Through abrasion released toxic components can lead to inflammatory reactions (Allen, 1997) Rigidity of metal implants reduces micromovements essential for fracture healing ( stress shielding ) Long time application can lead to implant loosening (Jacobs, 1998) Current metallic implants need a second operation for implant removal 9
10 10
11 Bioresorbable materials - a new approach No second operation for implant/sensor removal is necessary reduced morbidity reduced patient stress cost reduction for health care system by modulating for example the healing process 11
12 Collaboration partners Heraeus Technical University Vienna University of Natural Resources and Life Sciences Vienna Wien Leoben ETH Zürich Innsbruck Graz AT&S Leoben Medical University Innsbruck Technical University Graz Medical University Graz 12
13 Development of biodegradable Materials ETH Zurich Development of biodegradable metals Magnesium Iron Technical University Graz Development of biodegradable polymers Polyhydroxyalkanoats (PHA) 13
14 In vitro material testing Technical University Graz in vitro degradation testing Medical University Graz Cyto-viability tests 14
15 Material characterization Technical University Vienna Testing of mechanical properties AT&S Leoben Surface characterization Perthometer REM 15
16 In vivo studies Medical University Graz Continuous µct monitoring Blood examinations 16
17 Medical University Innsbruck Histomorphological analysis PHA, 17
18 In vivo studies University of Natural Resources and Life Sciences Vienna Screening of degradation products (LA-ICP-MS) 18
19 In vivo testing Technical University Vienna Push-out tests 19
20 PHB Poly(3-hydroxybutyrat) same mechanical properties as PLAs less environmental ph changes than PLAs produced by procaryontes (e.g. Bacillus megaterium) high purification methods reduce amount of endotoxin
21 Material 6 groups (n=6) of cylindrical pins (length: 8mm, diameter: 1,6mm) PHB PHB + 3% ZrO 2 (added to improve visualization in µct) PHB + 3% ZrO % Herafill (alternative bone material) Coatings of Mg-Alloys: PHB PHB with TBA connected PLDLA (Heraeus )
22 Methods µct Scans Histological slices
23 Micro CT BRIC - Bioresorbable Implants for Children
24 PHB Zr BRIC - Bioresorbable Implants for Children
25 PHB Zr sagittal 1m 6m 3m 9m
26 PHB Zr + 30% Herafill sagittal 1m 6m 3m 9m
27 Calculation Degradation PHB + Zr PHB + Zr + 10%H PHB + Zr + 30%H % Decrease per month bis 2,48 1,55 3,37 1,77 3,17
28 µct Implant Visualisation & 3D bone formation (6m) PHB PHB + Zr PHB+ Zr+ Herafill
29 Results µct Significant decrease of bone volume with ZrO2 in month 1 and 6 PHB + ZrO 2 (p=0,013)
30 Histological Slices Percentage of bone adherence on the implant length Zoom PHB + Zr + Herafill (6m)
31 Results Histological Slices Tendency of increasing bone adherence in samples with ZrO2 + Herafill in month 6 (p=0,012) Significant decrease of bone adherence with ZrO2 in month 6 (p=0,024)
32 Coatings of Mg-Alloy PHB (1w) PHB/TBA (1w) PLDLA (1w) PHB (4w) PHB/TBA (4w) PLDLA (4w)
33 Summary Addendums enable µct visualisation of PHB implants ZrO 2 decreases osteoconductive properties of PHB significantly Bone tissue formation can be improved by adding Herafill Coating not appropiate enough after 1w degradation and gas formation of alloy visible No differences between coatings
34 On-going fields of work Material improvement (crosslinking of PHAs, new metal alloy compositions) Implant surface modification (Micro-arc oxidation, coatings) Combination with additives to improve bone tissue reaction (Heraeus) In vivo models (rats, sheep and trauma models on brain and bone) 34
35 Thanks for your kind attention Techniker: Leopold Berger, Masterstudent, TU Wien Dipl.-Ing. Anna Celarek,PhD Studentin, TU Wien Dipl.-Ing. Dr. techn. Martin Koller, TU Graz Dipl.Ing. Martin Meischel, BoKu Wien Univ.Prof. Dipl.-Ing. Dr.techn. Franz Stelzer, TU Graz Ao.Univ.Prof. Dipl.-Ing. Dr.techn. Elmar Tschegg, TU Wien Univ.-Prof. i.r. Dr.phil. Stefanie Tschegg; BoKu Wien Ass.Prof. Dr.rer.nat. Frank Wiesbrock, TU Graz Forschung: Dipl.Biol, Dr.rer.nat. Heidi Schmitt Materialwissenschaftler: Dr Anja Hänzi, ETH Zürich Prof. Dr Peter Uggowitzer, ETH Zürich, Prof. Dr. Jörg Löffler, ETH Zürich Industriepartner: Dr. Andre Kobelt, Heraeus Dr. Klaus-Dieter Kühn, Heraeus Dr. Mario Krassnitzer, ATS Dr. Hannes Voraberger, ATS Chemikerin: Mag. Lisa Martinelli, PhD-Student, Med Uni Graz Mediziner: PD Dr Christoph Castellani, Ass.-Arzt, Meduni Graz Dr Peter Ferlic, Ass.Arzt, Med Uni Graz Dr Michael Fiedler, Ass. Arzt UKH Graz Dr Stefan Fischerauer, PhD-Student, Med Uni Graz Dr Tanja Kraus, OÄ, Meduni GrazDr.med.univ. Dr Karin Pichler, PhD-Student, Med Uni Graz Gustav Schmöller, Medizinstudent, Med Uni Graz Dr Eva Widni, Ass Ärztin, Med Uni Graz Dr Silvia Zötsch, Med Uni Graz Prof. Dr. Annelie Weinberg
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