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

作者:Pan, Haitao; Hao, Shaofei; Zheng, Qixin*; Li, Jingfeng; Zheng, Jin; Hu, Zhilei; Yang, Shuhua; Guo, Xiaodong; Yang, Qin
来源:Materials Science & Engineering C-Materials for Biological Applications, 2013, 33(6): 3336-3345.
DOI:10.1016/j.msec.2013.04.019

摘要

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.