title: A composited PEG-silk hydrogel combining with polymeric particles delivering rhBMP-2 for bone regeneration.
abstract: Given the fabulous potential of promoting bone regeneration, BMP-2 has been investigated widely in the bone tissue engineering field. A sophisticated biomaterial loaded with BMP-2, which could avoid the required supraphysiological dose leading to high medical costs and risks of complications, has been considered as a promising strategy to treat non-healing bone defects. In this study, we developed a simple approach to engineer a composited hydrogel consisting polymeric particles (PLA/PLGA) used as a BMP-2 delivery vehicle. Compared with other groups, the introduction of PLA into PEG-silk gels endowed the hydrogel new physicochemical characteristics especially hydrophobicity which inhibited the burst release of BMP-2 and enhanced gel's structural stability. Moreover, such composited gels could stabilize entrapped proteins and maintain their bioactivity fully in vitro. In vivo, the bio-degradability experiment demonstrated this system was biocompatible and the reinforced hydrophobicity significantly decreased degradation rate, and in rat critical-sized cranial defects model, the gel containing PLA promoted the most bone formation. These findings demonstrated the introduction of PLA changed physicochemical features of gels more suitable as a BMP-2 carrier indicated by inducing bone regeneration efficiently in large bone defects at low delivered dose and this system may own translational potential.
authors.affiliation: Department of Spine Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Dakun
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Spine Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Orthopedic Surgery, Heilongjiang, Provincial Hospital, Harbin, 150001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Orthopedic Surgery, Affiliated Hospital of Hebei University of Engineering, Hebei, 056002, China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Hard Tissue Development and Regeneration, Harbin Medical University, Harbin 150001, China. Electronic address: zhangbhyd@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; Institute of Hard Tissue Development and Regeneration, Harbin Medical University, Harbin 150001, China; China Orthopedic Regenerative Medicine (CORMed), Hangzhou, Zhejiang 310058, China. Electronic address: wangyansong1975@163.com.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D047011:Silk / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D047011:Silk; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: BMP-2 sustained release; Bio-composite; Bone regeneration; Hydrogel