Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration |
| |
| Authors: | Diederik HR Kempen Lichun Lu Andras Heijink Theresa E Hefferan Laura B Creemers Avudaiappan Maran Michael J Yaszemski Wouter JA Dhert |
| |
| Institution: | 1. Department of Oral and Maxillofacial Surgery, Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Craniomaxillofacial Surgery, School of Medicine, University of Antwerp, Antwerp, Belgiumo;3. Marquette University School of Dentistry, Milwaukee, WI 53233, USA;4. Dental Biomaterials Department, School of Dentistry, Tehran University of Medical Scien?ces, Tehran, Iran;5. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biologyand Technology, ACECR, Tehran, Iran;6. Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran;7. Biomaterials Group, Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran;8. Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK;1. Center for Biomaterials, Korea Institute of Science & Technology, Seoul 130-650, Republic of Korea;2. Department of Biomolecular Science, University of Science and Technology (UST), Seoul 136-791, Republic of Korea;3. Department of Pharmacology and Dental Therapeutics, and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea |
| |
| Abstract: | Bone regeneration is a coordinated cascade of events regulated by several cytokines and growth factors. Angiogenic growth factors are predominantly expressed during the early phases for re-establishment of the vascularity, whereas osteogenic growth factors are continuously expressed during bone formation and remodeling. Since vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs) are key regulators of angiogenesis and osteogenesis during bone regeneration, the aim of this study was to investigate if their sequential release could enhance BMP-2-induced bone formation. A composite consisting of poly(lactic-co-glycolic acid) microspheres loaded with BMP-2 embedded in a poly(propylene) scaffold surrounded by a gelatin hydrogel loaded with VEGF was used for the sequential release of the growth factors. Empty composites or composites loaded with VEGF and/or BMP-2 were implanted ectopically and orthotopically in Sprague–Dawley rats (n = 9). Following implantation, the local release profiles were determined by measuring the activity of 125I-labeled growth factors using scintillation probes. After 8 weeks blood vessel and bone formation were analyzed using microangiography, μCT and histology. The scaffolds exhibited a large initial burst release of VEGF within the first 3 days and a sustained release of BMP-2 over the full 56-day implantation period. Although VEGF did not induce bone formation, it did increase the formation of the supportive vascular network (p = 0.03) in ectopic implants. In combination with local sustained BMP-2 release, VEGF significantly enhanced ectopic bone formation compared to BMP-2 alone (p = 0.008). In the orthotopic defects, no effect of VEGF on vascularisation was found, nor was bone formation higher by the combination of growth factors, compared to BMP-2 alone. This study demonstrates that a sequential angiogenic and osteogenic growth factor release may be beneficial for the enhancement of bone regeneration. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
