The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to osteoprogenitor cell populations on bone formation

Kanczler, Janos, Ginty, P., White, L., Clarke, N., Howdle, S., Shakesheff, K. and Oreffo, R. (2010) The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to osteoprogenitor cell populations on bone formation. Biomaterials, 31 (6), 1241-1250. (doi:10.1016/j.biomaterials.2009.10.059).

Abstract

Regenerating bone tissue involves complex, temporal and coordinated signal cascades of which bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF165) play a prominent role. The aim of this study was to determine if the delivery of human bone marrow stromal cells (HBMSC) seeded onto VEGF165/BMP-2 releasing composite scaffolds could enhance the bone regenerative capability in a critical sized femur defect. Alginate-VEGF165/PDLLA-BMP-2 scaffolds were fabricated using a supercritical CO2 mixing technique and an alginate entrapment protocol. Increased release of VEGF165 (750.4 ± 596.8 ?g/ml) compared to BMP-2 (136.9 ± 123.4 ?g/ml) was observed after 7-days in culture. Thereafter, up till 28 days, an increased rate of release of BMP-2 compared to VEGF165 was observed. The alginate-VEGF165/PDLLA-BMP-2 + HBMSC group showed a significant increase in the quantity of regenerated bone compared to the alginate-VEGF165/PDLLA-BMP-2 and alginate/PDLLA groups respectively in a critical sized femur defect study as indices measured by ?CT. Histological examination confirmed significant new endochondral bone matrix in the HBMSC seeded alginate-VEGF165/PDLLA-BMP-2 defect group in comparison to the other groups. These studies demonstrate the ability to deliver a combination of HBMSC with angiogenic and osteogenic factors released from biodegradable scaffold composites enhances the repair and regeneration of critical sized bone defects.

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Contributors

Author: Janos Kanczler

Author: R. Oreffo

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