Abstract
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 invivo, 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 osteo-conductive 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 invivo, 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.
Original language | English (US) |
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Pages (from-to) | 5025-5035 |
Number of pages | 11 |
Journal | Biomaterials |
Volume | 34 |
Issue number | 21 |
DOIs | |
State | Published - Jul 2013 |
Externally published | Yes |
Keywords
- Angiogenesis
- Bone tissue engineering
- Mesenchymal stem cell
- Osteoclast
- Silicate-substituted apatite
- VEGF
ASJC Scopus subject areas
- Biophysics
- Bioengineering
- Ceramics and Composites
- Biomaterials
- Mechanics of Materials