Osteogenic/Angiogenic Dual Growth Factor Delivery Microcapsules for Regeneration of Vascularized Bone Tissue
- Authors
- Subbiah, Ramesh; Hwang, Mintai Peter; Van, Se Young; Do, Sun Hee; Park, Hansoo; Lee, Kangwon; Kim, Sang Heon; Yun, Kyusik; Park, Kwideok
- Issue Date
- 16-Sep-2015
- Publisher
- WILEY-BLACKWELL
- Keywords
- Bone regeneration; Dual growth factor delivery; Microcapsules; Nanoparticles; Umbilical cord, mesenchymal stem cells
- Citation
- ADVANCED HEALTHCARE MATERIALS, v.4, no.13, pp.1982 - 1992
- Journal Title
- ADVANCED HEALTHCARE MATERIALS
- Volume
- 4
- Number
- 13
- Start Page
- 1982
- End Page
- 1992
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10143
- DOI
- 10.1002/adhm.201500341
- ISSN
- 2192-2640
- Abstract
- Growth factors (GFs) are major biochemical cues for tissue regeneration. Herein, a novel dual GF delivery system is designed composed of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and alginate microcapsules (MCs) via an electrodropping method. While bone morphogenetic protein (BMP)-2 is encapsulated in the PLGA NPs, vascular endothelial growth factor (VEGF) is included in the alginate MCs, where BMP-2-loaded PLGA NPs are entrapped together in the fabrication process. The initial loading efficiencies of BMP-2 and VEGF are 78% +/- 3.6% and 43% +/- 1.7%, respectively. When our dual GF-loaded MCs are assessed for in vitro osteogenesis of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on 2D and 3D environment, MCs contribute to much better UCB-MSCs osteogenesis as confirmed by von Kossa staining, immunofluorescence (osteocalcin, collagen 1), calcium content measurement, and osteogenic markers expression. In addition, when dual GF-encapsulated MCs are combined with collagen and then applied to 8 mm diameter rat calvarial defect model, the positive effects on vascularized bone regeneration are much more pronounced; micro computed tomography (CT) and histology analyses exhibit 82.3% bone healing coupled with 12.6% vessel occupied area. Put together, current study indicates a synergistic effect of BMP-2/VEGF and highlights the great potential of dual GF delivery modality (PLGA NPs-in-MC) for regeneration of vascularized bone.
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