Journal
BIOMATERIALS
Volume 31, Issue 6, Pages 1242-1250Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2009.10.059
Keywords
Bone tissue regeneration; Human bone marrow stromal cells; Supercritical CO2; Critical sized femur defect; VEGF; BMP-2
Funding
- Engineering and Physical Sciences Research Council [GR/S27276/01]
- Engineering and Physical Sciences Research Council [EP/C534247/1, GR/S27276/01, GR/S27269/01] Funding Source: researchfish
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Regenerating bone tissue involves complex, temporal and coordinated signal cascades of which bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF(165)) play a prominent role. The aim of this study was to determine if the delivery of human bone marrow stromal cells (HBMSC) seeded onto VEGF(165)/BMP-2 releasing composite scaffolds could enhance the bone regenerative capability in a critical sized femur defect. Alginate-VEGF(165)/P(DL)LA-BMP-2 scaffolds were fabricated using a supercritical CO2 mixing technique and an alginate entrapment protocol. Increased release of VEGF(165) (750.4 +/- 596.8 rho g/ml) compared to BMP-2 (136.9 +/- 123.4 rho g/ml) was observed after 7-days in culture. Thereafter, up till 28 days, an increased rate of release of BMP-2 compared to VEGF(165) was observed. The alginate-VEGF(165)/P(DL)LA-BMP-2 + HBMSC group showed a significant increase in the quantity of regenerated bone compared to the alginate-VEGF(165)/P(DL)LA-BMP-2 and alginate/P(DL)LA groups respectively in a critical sized femur defect study as indices measured by mu CT. Histological examination confirmed significant new endochondral bone matrix in the HBMSC seeded alginate-VEGF(165)/P(DL)LA-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. (C) 2009 Elsevier Ltd. All rights reserved.
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