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

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 ρg/ml) compared to BMP-2 (136.9 ± 123.4 ρg/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 μCT. 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.