title: Bone induction by biomimetic PLGA copolymer loaded with a novel synthetic RADA16-P24 peptide in vivo.
abstract: Bone morphogenetic protein-2 (BMP-2) is a key bone morphogenetic protein, and poly(lactic-co-glycolic acid) (PLGA) has been widely used as scaffold for clinical use to carry treatment protein. In the previous studies, we have synthesized BMP-2-related peptide (P24) and found its capacity of inducing bone regeneration. In this research, we have synthesized a new amphiphilic peptide Ac-RADA RADA RADA RADA S[PO4]KIPKASSVPTELSAISTLYLDDD-CONH2 (RADA16-P24) with an assembly peptide RADA16-Ion the P24 item of BMP2 to form divalent ion-induced gelatin. Two methods of physisorption and chemical cross-linking were used to bind RADA16-P24 onto the surface of the copolymer PLGA to synthesize RADA16-P24-PLGA, and its capacity of attaching bone marrow stromal cells (BMSCs) was evaluated in vitro and inducing ectopic bone formation was examined in vivo. In vitro our results demonstrated that RADA16-P24-PLGA copolymer prepared by physisorbing or prepared by chemical cross-linking had a peptide binding rate of (2.0180±0.5296)% or (10.0820±0.8405)% respectively (P<0.05). In addition the BMSCs proliferated vigorously in the RADA16-P24-PLGA biomaterials. Significantly the percentage of BMSCs attached to RADA16-P24-PLGA composite prepared by chemical cross-linking and physisorbing were (71.4±7.5) % or (46.7±5.8) % (P<0.05). The in vivo study showed that RADA16-P24-PLGA chemical cross-linking could better induce ectopic bone formation compared with RADA16-P24-PLGA physisorbing and PLGA. It is concluded that the PLGA copolymer is a good RADA16-P24 carrier. This novel RADA16-P24-PLGA composite has strong osteogenic capability.
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Pan
authors.forename: Shaofei
authors.initials: S
authors.lastname: Hao
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zheng
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Hu
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008969:Molecular Sequence Data; D010012:Osteogenesis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds
chemical_list: D055396:Bone Morphogenetic Protein 2; D010455:Peptides; C546681:RADA16-I; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid