gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie, 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie

25. - 28.10.2011, Berlin

Osteoinductive potential and periimplant bone formation of immobilized rhBMP-2 on titanium implants in a gap healing model in sheep

Meeting Abstract

  • H.P. Jennissen - Institut für Physiologische Chemie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany
  • M. Chatzinikolaidou - Institute of Molecular Biology & Biotechnology, University of Crete, Heraklion Crete, Greece
  • T.K. Lichtinger - Orthopädische Universitätsklinik St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 75. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 97. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 52. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 25.-28.10.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocGR13-1113

doi: 10.3205/11dkou463, urn:nbn:de:0183-11dkou4638

Published: October 18, 2011

© 2011 Jennissen et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Questionnaire: Periimplant bone formation in vivo by recombinant human bone morphogenetic protein 2 (rhBMP-2) applied together with diverse carriers has only been variably successful or negative. These unsatisfactory results indicate that the mechanisms underlying bioactive BMP-2 coatings are yet only poorly understood. The present work attempts to shed some light on the mechanisms involved.

Methods: Ti-alloy-miniplates (Ti-6Al-4V, 10 x 5 x 1.6 mm) plated with cp titanium by plasma vapor deposition (PVD) and cylindrical PVD-plated Ti-alloy dumbbell shaped implants (length 10 mm) with a bar (length 7.5 mm, diam. = 5.0 mm) and a disk for fixation (diam. = 7 mm) at each end were used. rhBMP-2 was expressed in and prepared from E.coli. The surfaces were functionalized either with aminopropyltriethoxysilane (APS) alone or with APS followed by 1,1“-carbonyl diimidazole (CDI). The functionalized surfaces were then incubated for 12-14 h either in 2 ml 125I-rhBMP-2 (ca. 10 µCi/mg) or unlabelled rhBMP-2 (0.25-0.30 mg/ml). Three sheep (§8 of the Animal Protection law observed) received a total of 24 implants into the left and right distal femur condylus leaving a circular gap of ~1000 µm circumferentially around the bar. They were sacrificed after 4 and 9 weeks.

Results and Conclusions: rhBMP-2 (5-8 µg/cm2) was immobilized by two methods on porous PVD titanium surfaces (miniplates, dumbbell implants). Release of the immobilized 125I-rhBMP-2 from the surface occurred as an exponential decay in two-phases: a first rapid phase (ca. 15% of immobilized BMP-2) with half-lives of 1-2 days and a second slow sustained release phase (ca. 85% of immobilized BMP-2) with half-lives of 40-60 days. In spite of the very high binding constant (KA) of adsorbed rhBMP-2 estimated to be in the range of 1012 M-1 , the released rhBMP-2 was biologically active in vitro and in vivo. Osteoinductivity of rhBMP-2 coated implants was tested in vivo in a gap-healing model in the trabecular bone of the distal femur condylus of sheep. Neither inflammation nor capsule formation occurred during healing. The concentration of released rhBMP-2 in the 1 mm gap was calculated to 20-98 mM, well above the half-maximal response concentration (K0.5) of rhBMP-2 for inducing alkaline phosphatase in vitro in MC3T3-E1 cells. The bone density (BD) and bone-to-implant contact (BIC) of the implants explanted after 4 and 9 weeks were assessed histomorphometrically. Control implants without rhBMP-2 were not osseointegrated. Implants with immobilized rhBMP-2 displayed a significant 2-4 fold increase in BD and BIC values versus negative controls after 4-9 weeks. Integration of implants by trabecular bone was achieved after 4 weeks, indicating a mean "gap-filling rate" of ~250 µm/week. Integration of implants by cortical bone was observed after 9 weeks. We conclude that the enhancement of periimplant osseointegration and gap bridging by immobilized rhBMP-2 on implant surfaces is feasible and may serve as a model for future clinical applications.