Effect of rhBMP-2 and VEGF in a vascularized bone allotransplant experimental model based on surgical neoangiogenesis

Department of Orthopedics, University of São Paulo, Rua Dr Ovídio Pires de Campos, 333, Cerqueira Cesar, São Paulo, SP 05403-010, Brazil.
Journal of Orthopaedic Research (Impact Factor: 2.99). 04/2013; 31(4). DOI: 10.1002/jor.22277
Source: PubMed


We have demonstrated survival of living allogeneic bone without long-term immunosuppression using short-term immunosuppression and simultaneous creation of an autogenous neoagiogenic circulation. In this study, bone morphogenic protein-2 (rhBMP-2), and/or vascular endothelial growth factor (VEGF), were used to augment this process. Femoral diaphyseal bone was transplanted heterotopically from 46 Dark Agouti to 46 Lewis rats. Microvascular repair of the allotransplant nutrient pedicle was combined with intra-medullary implantation of an autogenous saphenous arteriovenous (AV) bundle and biodegradable microspheres containing buffer (control), rhBMP-2 or rhBMP-2 + VEGF. FK-506 given daily for 14 days maintained nutrient pedicle flow during angiogenesis. After an 18 weeks survival period, we measured angiogenesis (capillary density) from the AV bundle and cortical bone blood flow. Both measures were greater in the combined (rhBMP-2 + VEGF) group than rhBMP-2 and control groups (p < 0.05). Osteoblast counts were also higher in the rhBMP-2 + VEGF group (p < 0.05). A trend towards greater bone formation was seen in both rhBMP2 + VGF and rhBMP2 groups as compared to controls (p = 0.059). Local administration of VEGF and rhBMP-2 augments angiogenesis, osteoblastic activity and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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    • "In this regard, co-delivery of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) synergistically facilitates segmental bone healing [4] [5]. To repair massive bone defects , various tissue engineering approaches such as the use of osteoconductive scaffolds, osteoinductive growth factors and osteogenic cells have been explored alone or in combination. "
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