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 (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 CO(2) 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 r hog/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 microCT. 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.
Kanczler
Janos M
JM
Bone & Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Developmental Origins of Health and Disease, Institute of Developmental Sciences, University of Southampton, General Hospital, Southampton, SO16 6YD, UK.
Ginty
Patrick J
PJ
White
Lisa
L
Clarke
Nicholas M P
NM
Howdle
Steven M
SM
Shakesheff
Kevin M
KM
Oreffo
Richard O C
RO
D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D005264:Femoral Fractures / Q000473:pathology / Q000601:surgery*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004338:Drug Combinations; D042461:Vascular Endothelial Growth Factor A