title: Chitosan/nHAC/PLGA microsphere vehicle for sustained release of rhBMP-2 and its derived synthetic oligopeptide for bone regeneration.
abstract: Both of the osteogenic factor and the suitable delivery system in bone tissue engineering are essential for bone regeneration. In this study, we manufactured two kinds of composite vehicles for sustained release of rhBMP-2 and its derived synthetic oligopeptide (Peptide-24, abbreviated as P24) for osteogenesis and bone defect repair. The composite vehicle was based on cross-linked chitosan, nano-hydroxyapatite/collagen (nHAC), and poly (lactide-co-glycolide) acid microsphere. The physicochemical properties of the composite vehicles (abbreviated as CS/nHAC/PLGA-MS) were investigated. The rhBMP-2 and P24 release kinetics from the vehicles were examined and the secondary structure of rhBMP-2 and P24 after 28 days' release process was analyzed. In vitro cell proliferation, osteogenic differentiation and rat calvarial defect repair were evaluated. The results proved that the composite vehicle had favorable compressive strength, elastic modulus, the porosity, and the bulk density. The secondary structures of rhBMP-2 and P24 kept stability during microencapsulation and release process. P24 from the vehicle kept a geared-up release and rhBMP-2 from the vehicle kept a three-stage mode release process. The results of in vitro cell detection showed that the composite vehicle had good biocompatibility and osteoinduction. In vivo rat calvarial defect repair demonstrated that both groups of vehicles with rhBMP2 and P24 exhibited satisfied bone defect repair. This research showed that the composite vehicle could exhibit sustained release of osteogenic factors. CS/nHAC/PLGA-MS loading rhBMP-2 or P24 could be a novel and ideal scaffold for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1593-1606, 2017.
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, China.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen, 518057, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Tingfang
authors.initials: T
authors.lastname: Sun
authors.affiliation: Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives*; D003094:Collagen / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000293:injuries; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D010455:Peptides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C509317:nano-hydroxyapatite-collagen; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D048271:Chitosan; D017886:Durapatite
keywords: CS/nHAC/PLGA-MS; bone regeneration; bone tissue engineering; rhBMP-2 derived peptide; sustained release