title: Osteogenic/angiogenic dual growth factor delivery microcapsules for regeneration of vascularized bone tissue.
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.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-333, South Korea.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subbiah
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.
authors.forename: Mintai Peter
authors.initials: MP
authors.lastname: Hwang
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-333, South Korea.
authors.forename: Se Young
authors.initials: SY
authors.lastname: Van
authors.affiliation: Department of Veterinary Clinical Pathology, Konkuk University, Seoul, 143-701, South Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Do
authors.affiliation: School of Integrative Engineering, Chung-Ang University, Seoul, 156-756, South Korea.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Park
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-333, South Korea.
authors.forename: Kangwon
authors.initials: K
authors.lastname: Lee
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-333, South Korea.
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Bionanotechnology, Gachon University, Seongnam, 461-701, South Korea.
authors.forename: Kyusik
authors.initials: K
authors.lastname: Yun
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejon, 305-333, South Korea.
authors.forename: Kwideok
authors.initials: K
authors.lastname: Park
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001847:Bone Diseases / Q000628:therapy; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002214:Capsules / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D002214:Capsules; D004337:Drug Carriers; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid
keywords: bone regeneration; dual growth factor delivery; microcapsules; nanoparticles; umbilical cord, mesenchymal stem cells