Bioinspired Growth of Hydroxyapatite Nanocrystals on PLGA- (PEG- ASP)n Scaffolds Modified with Oligopeptide Derived from BMP-2

Abstract

Natural bone is a typical example of an “organic matrix-mediated” biomineralization process which constituted of hydroxyapatite(HA) nanocrystals orderly grown in intimate contact with collagen fibers. Bone morphogenetic protein 2 (BMP2) is the most powerful osteogenic factor. But it is extremely difficult to be manufactured in large scale. In previous study, we have designed a novel oligopeptide (P24) derived from BMP2 knuckle epitope and it contained abundant Asp(aspartic acid) and phosphorylated Ser(serine) which may be helpful for self-assambly biomineralization and osteogenesis. Previous In vivo experiments have shown that this novel oligopeptide had excellent osteoinductive and ectopic bone formation property which was similar to that of BMP2. In this study, PLGA-(PEG-ASP)n scaffolds were modified with P24 and a new biomimetic bone tissue engineering scaffold material with enhanced bioactivity was synthesized by a biologically inspired mineralization approach. Peptide P24 was introduced into PLGA-(PEG-ASP)n scaffolds using cross-linkers. Then the P24 modified scaffolds and the simple PLGA-(PEG-ASP)n scaffolds were incubated in modified simulated body fluid (mSBF) for 10 days. Growth of HA nanocrystals on the materials was confirmed by observation SEM and measurements EDS and XRD. SEM analysis demonstrated the well growth of bonelike HA nanocrystals on P24 modified PLGA-(PEG-ASP)n scaffolds than that of the control scaffolds. The main component of mineral of the P24 modified scaffolds was hydroxyapatite containing low crystalline nanocrystals, and the Ca/P ratio was nearly 1.60, similar to that of natural bone, while that of the control scaffolds was 1.52. The introduction of peptide P24 into PLGA- (PEG- ASP)n copolymer provides abundant active sites to mediate the nucleation and self- ssembling of HA nanocrystals in mSBF. the resulted peptide P24 modified- HA/PLGA- (PEG- ASP)n composite shows some features of natural bone both in main composition and and hierarchical microstructure. This biomimetic treatment provides a simple method for surface functionalization and subsequent biomineralization on biodegradable polymer scaffolds for tissue engineering.