Bone induction by biomimetic PLGA copolymer loaded with a novel synthetic RADA16-P24 peptide in vivo

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• 作者：Haitao Pan^a ; ¹ ; Shaofei Hao^a ; ¹ ; Qixin Zheng^a ; ^{zheng-qx@163.com} ; Jingfeng Li^a ; ^b ; Jin Zheng^a ; Zhilei Hu^a ; Shuhua Yang^a ; Xiaodong Guo^a ; Qin Yang^c
• 关键词：PLGA copolymer ; RADA16-P24 peptide ; Assembly ; Ectopic bone formation
• 刊名：Materials Science and Engineering: C
• 出版年：2013
• 出版时间：1 August, 2013
• 年：2013
• 卷：33
• 期：6
• 页码：3336-3345
• 全文大小：1659 K

文摘

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 ¡À 0.5296) % or (10.0820 ¡À 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 ¡À 7.5) % or (46.7 ¡À 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.