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Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect
Affiliation:1. Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China;2. Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China;3. CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168, Australia;4. Department of Prosthodontics, College of Stomatology, Ninth People''s Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, PR China;1. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;2. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;3. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;4. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical sciences, Mashhad, Iran;5. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. Department of Biomedical Engineering, University of South Dakota, BioSNTR, Sioux Falls, SD 57107, USA;2. School of Ophthalmology and Optometry, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, China;3. Institute of Advanced Materials for Nano-Bio Applications, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;4. Department of Chemistry, University of South Dakota, 414 E. Clark Street, Vermillion 57069, SD, USA
Abstract:There is an urgent need to develop biomimetic bone tissue engineering scaffolds for the repair of critical-sized calvarial defect. In this study, we developed a new nanoparticle-embedded electrospun nanofiber scaffold for the controlled dual delivery of BMP-2 and dexamethasone (DEX). The scaffold was achieved by (1) the encapsulation of BMP-2 into bovine serum albumin (BSA) nanoparticles to maintain the bioactivity of BMP-2 and (2) the co-electrospinning of the blending solution composed of the BSA nanoparticles, DEX and the poly(ε-caprolactone)-co-poly(ethylene glycol) (PCE) copolymer. The in vitro studies showed that the bioactivity of DEX and BMP-2 was preserved in the dual-drug-loaded nanofiber scaffold, and a sequential release pattern in which most of the DEX was released in the original eight days and the BMP-2 release lasted up to 35 days was achieved. The in vitro osteogenesis study demonstrated that the drug-loaded groups exhibited a strong ability to induce differentiation toward osteoblasts. In vivo osteogenesis studies also revealed that the degrees of repair of rat calvarial defect achieved with the drug-loaded nanofiber scaffolds were significantly better than those obtained with the blank materials; in particular, the dual-drug-loaded nanofiber scaffold manifested the best repair efficacy due to a synergistic effect of BMP-2 and DEX. Therefore, the dual-drug-loaded nanofiber scaffold is deemed a strong potential candidate for the repair of bone defects in bone tissue engineering.
Keywords:Nanofiber  Electrospinning  Critical bone defect  Nanoparticle  Drug delivery  Tissue engineering
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