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Tissue Eng Part A. 2011 Dec;17(23-24):2911-8. doi: 10.1089/ten.tea.2010.0584. Epub 2011 Aug 26.

Antibody-mediated osseous regeneration: a novel strategy for bioengineering bone by immobilized anti-bone morphogenetic protein-2 antibodies.

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Laboratory of Immune Regulation and Tissue Engineering, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA.


Bone regeneration often requires harvesting of autologous bone with significant potential morbidity and cost. Recombinant human bone morphogenetic protein (rhBMP)-2 has been approved by the U.S. Food and Drug Administration for specific regenerative indications. However, administration of exogenous growth factors has many drawbacks. The objective of the present proof-of-concept study was to determine whether immobilized anti-BMP-2 antibodies (Abs) could capture endogenous BMP-2 in local sites to mediate osteogenesis, a strategy we refer to as antibody-mediated osseous regeneration (AMOR). We have generated a murine anti-BMP-2 monoclonal antibody library, which was tested along with commercially available Abs in vitro and in vivo for their ability to mediate AMOR. In vitro studies demonstrated that only some anti-BMP-2 Abs tested formed immune complexes with BMP-2, which can bind to BMP cellular receptor, whereas other BMP-2/anti-BMP-2 complexes failed to bind. To investigate whether anti-BMP-2 Abs were able to mediate AMOR in vivo, anti-BMP-2 Abs were immobilized on absorbable collagen sponge (ACS) and surgically placed in rat calvarial defects. Microcomputed tomography analysis of live animals at 2, 4, and 6 weeks demonstrated that some anti-BMP-2 Abs immobilized on ACS mediated significant bone regeneration, whereas other clones did not mediate any bone regeneration. In situ BMP-2 and osteocalcin expression was investigated by immunohistochemistry. Results demonstrated higher BMP-2 and osteocalcin expression in sites with increased bone regeneration. Results provide first evidence for the ability of anti-BMP2 Abs to form an immune complex with endogenous BMP-2 and mediate bone regeneration in vivo, suggesting a promising therapeutic method for tissue engineering.

[Indexed for MEDLINE]

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