Polydopamine-assisted BMP-2-derived peptides immobilization on biomimetic copolymer scaffold for enhanced bone induction in vitro and in vivo

Abstract

In this study, a polydopamine (pDA)-coated PLGA-[Asp-PEG]n scaffold was developed for sustained delivery of bone morphogenetic protein-2 (BMP-2)-derived peptide (designated as P24), and then used to address the hypothesis that P24 peptides delivered from the scaffolds could enhance bone induction in vitro and in vivo. We found pDA coating as compared with physical adsorption could more efficiently mediate the grafting of peptides onto polymer surfaces, and the release of P24 peptides from PLGA-[Asp-PEG]n-pDA-P24 was sustained for about 21 days, while a burst P24 release was observed in initial 4h and almost all peptides were released within 24h in physisorbed PLGA-[Asp-PEG]n-P24 group. In vitro, significantly greater ALP activity and mRNA expressions of osteo-specific markers of rat-derived mesenchymal stem cells (rMSCs) were observed in the sustained delivery system than those in physisorbed PLGA-[Asp-PEG]n-P24 and unmodified PLGA-[Asp-PEG]n groups. In vivo, ectopic bone formation studies showed that the sustained delivery system could induce bone formation to a much greater extent than physisorbed PLGA-[Asp-PEG]n-P24. Meanwhile, there were no evidences of bone formation in non-P24-loaded PLGA-[Asp-PEG]n. It is concluded that PLGA-[Asp-PEG]n-pDA-P24 biomaterial can delivery bioactive P24 peptides in a sustained manner, which can more efficiently promote osteogenic differentiation of rMSCs in vitro and induce ectopic bone formation in vivo, as compared with PLGA-[Asp-PEG]n-P24 delivering P24 in a burst manner. This pDA-coated PLGA-[Asp-PEG]n-pDA-P24 composite promises to be an excellent biomaterial for inducing bone regeneration. Moreover, pDA-mediated catechol functionalization can be an effective, simple technique for developing sustained delivery systems.