Dose Effect of Dual Delivery of Vascular Endothelial Growth Factor and Bone Morphogenetic Protein-2 on Bone Regeneration in a Rat Critical-Size Defect Model
- 1 September 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 15 (9), 2347-2362
- https://doi.org/10.1089/ten.tea.2008.0510
Abstract
The dose effect of dual delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) on bone regeneration was investigated in a rat cranial critical-size defect (CSD). It was hypothesized that decreasing amounts of BMP-2 would result in a dose-dependent decrease in bone formation, and that this reduction in bone formation could be reversed by adding increasing amounts of VEGF. In vitro release kinetics of VEGF or BMP-2 were examined over 28 days. Next, scaffolds were implanted within a rat cranial CSD containing different combinations of both BMP-2 and VEGF. At 12 weeks, samples were analyzed using microcomputed tomography and histology. In vitro, VEGF and BMP-2 exhibited burst release in the first 24 h followed by a significant decrease in release rate over 27 days. Overall, BMP-2 had a more sustained release versus VEGF. An in vivo dose-dependent decrease in percentage of bone fill (PBF) was observed for BMP-2. The addition of VEGF was unable to reverse this decrease in PBF, although improvements in the number of bridged defects did occur in some groups. This suggests that for this particular model simultaneous release of BMP-2 and VEGF does not increase bone formation over BMP-2 alone at 12 weeks.Keywords
This publication has 65 references indexed in Scilit:
- Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect modelBone, 2008
- Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2Acta Biomaterialia, 2008
- Angiogenesis in bone fracture healing: A bioregulatory modelJournal of Theoretical Biology, 2008
- Muscle-derived stem cells for tissue engineering and regenerative therapyBiomaterials, 2007
- Endostatin inhibits endochondral ossificationThe Journal of Gene Medicine, 2007
- Fabrication of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineeringBiomaterials, 2007
- Solid lipid templating of macroporous tissue engineering scaffoldsBiomaterials, 2007
- A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE® Bone Graft)International Orthopaedics, 2007
- Segmental bone regeneration using a load-bearing biodegradable carrier of bone morphogenetic protein-2Biomaterials, 2007
- Synergistic enhancement of bone formation and healing by stem cell–expressed VEGF and bone morphogenetic protein-4JCI Insight, 2002