SFB 599:  Sustainable Bioresorbable and Permanent Implants of Metallic and Ceramic Materials

• Subject Area: Medicine ; Materials Science and Engineering
• Term: from 2003 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485789

• Final Report Year: 2017

Final Report Abstract

The Collaborative Research Center SFB 599 was a transdisciplinary research alliance of the Hannover Medical School, the Leibniz University of Hannover, the University of Veterinary Medicine Hannover, the Laser Zentrum Hannover e.V., the Technische Universität Braunschweig and the Helmholtz Centre for Infection Research in Braunschweig. The SFB 599 was dedicated to basic research for sustainable medical implants of metallic and ceramic materials during the period of 2003 to 2014 covering different clinical application areas such as otorhinolaryngology, othopaedics, trauma surgery, cardiac surgery and dental prosthetics. The research alliance adressed a multitude of scientific issues around the development chain of medical implants: Functional design, material science, manufacturing technology, simulation and testing (in vitro and in vivo). Improvement of biocompatibility, biofunctionality and biointegration were important goals of the research. For permanent implants, the focus was on the improvement of the interface between implant surface and biological tissue. A variety of surface functionalizations of physical, chemical, biochemical and cellular nature have been developed in order to reduce the trauma reaction (fibrosis), avoid postoperative infections and formation of detrimental biofilms and to stimulate the integration into the target tissue. Further, resorbable implants based on magnesium alloys have been investigated for aplications (e.g. bone fractures) for which the implant has to fulfill its function only for a limited period of time. until the body has recovered. Transdisciplinary imteraction between nature sciences, material sciences, production technology, cell biology, human and veterinary medicine was a striking feature of the SFB 599 which was reflected in the thematic variety of the participating clinics and (universitary) research institutes. This way, the whole process and innovation chain was represented by the research partners reaching from basic research to translational projects. The SFB 599 was a nucleus for sustainable interdisciplinary implant research in Hannover, linking together Hannover´s the three universities and other excellent regional research partners.

Publications

• Synthesis and Characterization of Biocompatible Polymer Interlayers on Titanium Implant Materials, Biomacromolecules 7, 2552 -2559 (2006)
  N. Adden, L. J. Gamble, D. G. Castner, A. Hoffmann, G. Gross, H. Menzel
  (See online at https://dx.doi.org/10.1021/bm060473j)
• (2009): “Numerical investigations on the strain-adaptive bone remodelling in the periprosthetic femur: influence of the boundary conditions” Biomedical Engineering online 8, S. 7
  Behrens, B.-A.; Nolte, I.; Wefstaedt, P.; Stukenborg-Colsman, C.; Bouguecha, A.
  
• System for the determination of molecules altering the function of interferon, method therefore and compounds altering interferon activity. EP2138185 A1. Anmeldung, Veröffentlichungsdatum 30.12.2009
  Pulverer J, Köster M, Sasse, F, Hauser H
  
• (2010) Electromagnetic induction heating of an orthopaedic nickel-titanium shape memory device. J Orthop Res 28:1671-6
  Müller CW, Pfeifer R, El-Kashef T, Hurschler C, Herzog D, Oszwald M, Haasper C, Krettek C, Gösling T
  
• Ductile and brittle material removal mechanisms in natural nacre—A model for novel implant materials, Journal of Materials Processing Technology 210 (2010) 1827-1837
  B. Denkena, J. Koehler, A. Moral
  (See online at https://dx.doi.org/10.1016/j.j matprotec.2010.06.014)
• Mesenchymal Stem Cell-Dependent Formation of Heterotopic Tendon-Bone Insertions (Osteotendinous Junctions). Stem Cells. 28, 1590-1601 (2010)
  S. Shahab-Osterloh, F. Witte, A. Hoffmann, A. Winkel, S. Laggies, B. Neumann, V. Seiffart, W. Lindenmaier, A.D. Gruber, J. Ringe, T. Häupl, F. Thorey, E. Willbold, P. Corbeau, G. Gross
  
• (2011) A preliminary study of bending stiffness alteration in shape changing nitinol plates for fracture fixation. Annals of biomedical engineering 39:1546-54
  Ölender G, Pfeifer R, Müller CW, Gösling T, Barcikowski S, Hurschler C
  
• (2011) Determination of dynamically adapting anisotropic material properties of bone under cyclic loading. J Biomech 44:272-276
  Besdo S
  
• (2011) The use of an in vitro-cultured porcine nasal mucosa model for the biocompatibility assessment of biodegradable magnesium. ATLA 39(3):261-71
  Schumacher S, Stahl J, Bäumer W et al.
  
• Amino-modified silica surfaces efficiently immobilize bone morphogenetic protein 2 (BMP2) for medical purposes, Acta Biomater. 7 (2011) 1772-1779
  N. Ehlert, A. Hoffmann, T. Luessenhop, G. Gross, P.P. Mueller, M. Stieve, T. Lenarz, P. Behrens
  
• Coating of titanium implant materials with thin polymeric films for binding the signaling protein BMP2 Macromol. Biosci. 11, 234-244 (2011)
  C. Lorenz, A. Hoffmann, G. Gross, H. Windhagen, P. Dellinger, K. Möhwald, W. Dempwolf, H. Menzel
  (See online at https://dx.doi.org/10.1002/mabi.201000342)
• Mechanical Characterization of Nacre an as Ideal-Model for Innovative new Endoprothesis Materials Arch. Ortho. Trauma Surgery 131 (2), 191-196 (2011)
  B. I. Richter, C. Hurschler, S. Kellner, H. Menzel, P. Behrens, B. Denkena, S. Ostermeier
  (See online at https://dx.doi.org/10.1007/s00402-010-1118-z)
• Mesoporous Silica Coatings for Controlled Release of the Antibiotic Ciprofloxacin from Implants, J. Mater. Chem. 21 (2011) 752-760
  N. Ehlert, M. Badar, A. Christel, S.J. Lohmeier, T. Luessenhop, M. Stieve, T. Lenarz, P.P. Mueller, P. Behrens
  
• Supporting element for tissue implants, WO 2011/101142 A1. Anmeldung, Veröffentlichungsdatum 25.8.2011
  Bach F-W, Haverich A, Cebotari S, Biskup C, Schuster B
  
• (2012) Histological and molecular evaluation of iron as degradable medical implant material in a murine animal model. J Biomed Mater Res A 100(11):2881-9
  Mueller PP, Arnold S, Badar M et al.
  (See online at https://doi.org/10.1002/jbm.a.34223)
• (2012) Low temperature degradation of different zirconia ceramics for dental applications. Acta Biomater 8:1213-1220
  Kohorst P, Borchers L, Strempel J, Stiesch M, Hassel T, Bach Fr-W, Hübsch C
  (See online at https://doi.org/10.1016/j.actbio.2011.11.016)
• (2012): Characterization of MgNd2 alloy for potential applications in bioresorbable implantable devices, In: Acta Biomaterialia 8 (10), S. 3852-3864
  Seitz, J.-M.; Eifler, R.; Stahl, J.; Kietzmann, M.; Bach, Fr.-W.
  (See online at https://doi.org/10.1016/j.actbio.2012.05.024)
• (2012): “Bone remodeling after total hip arthroplasty with a short stemmed metaphyseal loading implant: Finite element analysis validated by a prospective DEXA investigation” J Orthop Res 30:1822-1829, 2012
  Lerch, M.; Kurtz, A.; Stukenborg-Colsman, C.; Nolte, I.; Weigel, N.; Bouguecha, A.; Behrens, B.-A.
  (See online at https://doi.org/10.1002/jor.22120)
• Fabrication and characterization of nacre like structures from a-Zirconium hydrogenphosphate hydrate and chitosan J. Colloid Interface Sci. 367 (1), 74-82 (2012)
  S. Waraich, B. Hering, Z. Burghard, J. Bill, P. Behrens, H. Menzel
  (See online at https://doi.org/10.1016/j.jcis.2011.10.042)
• (2013) A Roughness Model for the Machining of Bio-medical Ceramics by T oric Grinding Pins. CIRP J Manuf Sci Technol 6(1):22-33
  Denkena B, Köhler J, van der Meer M
  (See online at https://dx.doi.org/10.1016/j.cirpj.2012.07.002)
• (2013) Development, Simulation-Based Design and Metal Forming Production of Patient-Individual Hip Cups. In: Schuh G, Neugebauer R, Uhlmann E (Hrsg) Future Trends in Production Engineering. Springer Berlin Heidelberg, Berlin, Heidelberg, S 307-314
  Behrens B, Weigel N, Escobar SB, Stukenborg-Colsman C, Lerch M, Nolte I, Wefstaedt P, Bouguecha A
  
• (2013) Long term in vivo degradation behaviour and biocompatibility of the magnesium alloy ZEK100 for use as biodegradable bone implant. Acta Biomat 9:8548-8560
  Dziuba D, Meyer-Lindenberg A, Seitz JM, Waizy H, Angrisani N, Reifenrath J
  (See online at https://doi.org/10.1016/j.actbio.2012.08.028)
• (2013) Manufacturing conditioned roughness and wear of biomedical oxide ceramics for all-ceramic knee implants. Biomed Eng Online 12(84)
  Turger A, Köhler J, Denkena B, Correa TA, Becher C, Hurschler C
  (See online at https://doi.org/10.1186/1475-925X-12-84)
• (2013) Noninvasive induction implant heating: An approach for contactless altering of mechanical properties of shape memory implants. Med Eng Phys 35:54-62
  Pfeifer R, Hustedt M, Wesling V, Hurschler C, Olender G, Mach M, Gösling T, Müller CW
  (See online at https://doi.org/10.1016/j.medengphy.2012.03.010)
• (2013) The formation of an organic coat and the release of corrosion microparticles from metallic magnesium implants. Acta Biomater 9(7):7580-9
  Badar M, Lünsdorf H, Evertz F et al.
  (See online at https://doi.org/10.1016/j.actbio.2013.03.012)
• (2013), 'Evaluation of single-cell force spectroscopy and fluorescence microscopy to determine cell interactions with femtosecond-laser microstructured titanium surfaces', Journal of Biomedical Materials Research Part A 101A(4), 981-990
  Aliuos, P.; Fadeeva, E.; Badar, M.; Winkel, A.; Mueller, P. P.; Warnecke, A.; Chichkov, B.; Lenarz, T.; Reich, U. & Reuter, G.
  (See online at https://doi.org/10.1002/jbm.a.34401)
• (2013), 'Topography and Coating of Platinum Improve the Electrochemical Properties and Neuronal Guidance', ACS Applied Materials & Interfaces 5(3), 1070-1077
  Schlie-Wolter, S.; Deiwick, A.; Fadeeva, E.; Paasche, G.; Lenarz, T. & Chichkov, B. N.
  (See online at https://doi.org/10.1021/am3028487)
• Adaptations in muscle activity to induced, short-term hindlimb lameness in trotting dogs. PlosOne 8(11): e80987, 2013
  Fischer S, Nolte I, Schilling N
  (See online at https://doi.org/10.1371/journal.pone.0080987)
• Efficacy of nanoporous silica coatings on middle ear prostheses as a delivery system for antibiotics: An animal study in rabbits, Acta Biomater. 9 (2013) 4815-4825
  R. Lensing, A. Bleich, A. Smoczek, S. Glage, N. Ehlert, T. Luessenhop, P. Behrens, P.P. Müller, M. Kietzmann, M. Stieve
  (See online at https://doi.org/10.1016/j.actbio.2012.08.016)
• Light activated hearing aid device. US8545383 B2 Prioritätsdatum: 30.1.2009, Veröffentlichungsdatum 1.10.2013
  Wenzel G, Lim H, Lenarz T, Lubatschowski H:
  
• Mesoporous silica films as a novel biomaterial: applications in the middle ear, Chem. Soc. Rev. 42 (2013) 3847-3861
  N. Ehlert, P.P. Mueller, M. Stieve, T. Lenarz, P. Behrens
  (See online at https://doi.org/10.1039/c3cs35359a)
• The selective role of extracellular matrix components on cell adhesion, morphology, proliferation and communication in vitro. Exp. Cell Research 319: 1553-1561 (2013)
  S. Schlie-Wolter, A. Ngezahayo, B. Chichkov
  
• Verfahren zur Herstellung eines Elements aus einem Magnesiumwerkstoff und so herstellbares Element. EP20080866172 B1. Erteilung, Veröffentlichungsdatum 22.5.2013
  Bach F-W, Kucharski R, Bormann D
  
• (2014) Biodegradation of metallic magnesium elicits an inflammatory response in primary nasal epithelial cells. Acta Biomater 10(2):996-1004
  Schumacher S, Roth I, Stahl Jet al.
  (See online at https://doi.org/10.1016/j.actbio.2013.10.030)
• (2014) Biodegradation of metallic magnesium elicits an inflammatory response in primary nasal epithelial cells. Acta Biomater 10:996-1004
  Schumacher S, Roth I, Stahl J et al
  (See online at https://doi.org/10.1016/j.actbio.2013.10.030)
• (2014) Comparative in vitro study and biomechanical testing of two different magnesium alloys. J Biomat Appl 28(8):1264-1273
  Weizbauer A, Modrejewski C, Behrens S, Klein H, Helmecke P, Seitz JM, Windhagen H, Möhwald K, Reifenrath J, Waizy H
  (See online at https://doi.org/10.1177/0885328213506758)
• (2014), 'Impact of laser-structured biomaterial interfaces on guided cell responses', Interface Focus 4, 20130048
  Fadeeva, E.; Deiwick, A.; Chichkov, B. & Schlie-Wolter, S.
  (See online at https://doi.org/10.1098/rsfs.2013.0048)
• (2014): Geometric adaption of biodegradable magnesium alloy scaffolds to stabilise bio-logical myocardial grafts. Part I, Journal of Materials Science: Materials in Medicine (Springer Verlag), Volume 25, S. 909-916
  M. Bauer, T. Schilling, M. Weidling, D. Hartung, Ch. Biskup, P. Wriggers, F. Wacker, Fr. -W. Bach, A. Haverich, T. Hassel
  (See online at https://doi.org/10.1007/s10856-013-5100-5)
• (2014):”Production of patient-individual hip cups by sheet metal forming: Simulation-based planning and metal forming adapted design method“ AMR907, S.253-264
  Behrens, Bernd Arno; Betancur Escobar, Stefanie; Almohallami, Amer; Weigel, Nelly; Vucetic, Milan; Stukenborg-Colsmann, Christina; Lerch, Matthias; Nolte, Ingo; Lucas, Karin; Wefstaedt, Patrick; Bouguecha, Anas
  (See online at https://doi.org/10.4028/www.scientific.net/AMR.907.253)
• 2014. In vivo degradation effects of alloy MgNd2 in contact with mucous tissue. J Biomed Mater Res Part A 2014
  Seitz, J.-M., Eifler, R., Weber, C., Lenarz, T.H., Maier, H.J., Durisin, M.
  (See online at https://doi.org/10.1002/jbm.a.35382)
• (2015) Degradation behaviour of LAE442-based plate-screw-systems in an in vitro bone model. Mat Sci Eng C 49:305-315
  Wolters L, Besdo S, Angrisani N, Wriggers P, Hering B, Seitz JM, Reifenrath J
  (See online at https://doi.org/10.1016/j.msec.2015.01.019)
• (2015) Protection of yttria-stabilized zirconia for dental applications by oxidic PVD coating. Acta Biomater 11:488-493
  Hübsch C, Dellinger P, Maier HJ, Stemme F, Bruns M, Stiesch M, Borchers L
  (See online at https://doi.org/10.1016/j.actbio.2014.09.042)
• (2015): Development of Magnesium Alloy Scaffolds to Support Biological Myocardial Grafts: A Finite Element Investigation, Lenarz, T.; Wriggers, P. (Hg.): Biomedical Technology, Publishing Lecture Notes in Applied and Computational Mechanics 74, Springer International Publishing, Switzerland, S. 81-100
  Weidling, M.; Besdo, S.; Schilling, T.; Bauer, M.; Hassel, T.; Bach, F.-W.; Maier, H. J.; Lamon, J.; Haverich, A.; Wriggers, P.
  (See online at https://dx.doi.org/10.1007/978-3-319-10981-7_6)
• Biocompatibility of MgF2-coated MgNd2 specimens in contact with mucosa of the nasal sinus - A long term study. Acta Biomater (2015)
  Weber, C.-M., Eifler, R., Seitz, J.-M., Maier, H. J., Reifenrath, J., Lenarz, T., Durisin, M.
  (See online at https://dx.doi.org/10.10167j.actbio.2015.03.003)
• Verfahren zur Herstellung eines Bauteils und Abutment. DE102014113177 B4. Erteilung, Veröffentlichungsdatum 7.4.2016
  Stiesch M, Borchers L, Hübsch C, Dellinger P, Möhwald K, Maier HJ