Journal
BIOMATERIALS
Volume 34, Issue 21, Pages 5025-5035Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.03.040
Keywords
Angiogenesis; Bone tissue engineering; Mesenchymal stem cell; Osteoclast; Silicate-substituted apatite; VEGF
Funding
- Department of Surgery (Basel University Hospital)
- European Union [CP-IP 214685]
- Swiss National Science Foundation [127426, 143898, 120432, 138519]
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Rapid vascularisation of tissue-engineered osteogenic grafts is a major obstacle in the development of regenerative medicine approaches for bone repair. Vascular endothelial growth factor (VEGF) is the master regulator of vascular growth. We investigated a cell-based gene therapy approach to generate osteogenic grafts with an increased vascularization potential in an ectopic nude rat model in vivo, by genetically modifying human bone marrow-derived stromal/stem cells (BMSC) to express rat VEGF. BMSC were loaded onto silicate-substituted apatite granules, which are a clinically established osteoconductive material. Eight weeks after implantation, the vascular density of constructs seeded with VEGF-BMSC was 3-fold greater than with control cells, consisting of physiologically structured vascular networks with both conductance vessels and capillaries. However, VEGF specifically caused a global reduction in bone quantity, which consisted of thin trabeculae of immature matrix. VEGF did not impair BMSC engraftment in vivo, but strongly increased the recruitment of TRAP- and Cathepsin K-positive osteoclasts. These data suggest that VEGF over-expression is effective to improve the vascularization of osteogenic grafts, but also has the potential to disrupt bone homoeostasis towards excessive degradation, posing a challenge to its clinical application in bone tissue engineering. (C) 2013 Elsevier Ltd. All rights reserved.
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