In vivo osteogenic response to different ratios of BMP-2 and VEGF released from a biodegradable porous system

Bone regeneration and vascularization with porous PLGA scaffolds loaded with VEGF (0.35 and 1.75 mu g) and BMP-2 (3.5 and 17.5 mu g), incorporated in PLGA microspheres, or the combination of either dose of BMP-2 with the low dose of VEGF were investigated in an intramedullary femur defect in rabbits. The system was designed to control growth factor (GF) release and maintain the GFs localized within the defect. An incomplete release was observed in vitro whereas in vivo VEGF and BMP-2 were totally delivered during 3 and 4 weeks, respectively. A weak synergistic effect of the dual delivery of VEGF and BMP-2 (high dose) was found by 4 weeks. However, the absence of an apparent synergistic long-term effect (12 weeks) of the combination over BMP-2 alone suggests that more work has to be done to optimize VEGF dose, sequential presentation, and the ratio of the two GFs to obtain a beneficial bone repair response. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 23822391, 2012.