Improving osteogenesis of three-dimensional porous scaffold based on mineralized recombinant human-like collagen via mussel-inspired polydopamine and effective immobilization of BMP-2-derived peptide

Abstract

An ideal bone substitute should be biocompatible, biodegradable, osteoinductive and osteoconductive. In our previous work, we fabricated a three-dimensional porous scaffold based on mineralized recombinant human-like collagen, nano-hydroxyapatite/recombinant human-like collagen/poly(lactic acid) (nHA/RHLC/PLA). Like other HA/collagen scaffolds, the nHA/RHLC/PLA scaffold lacked osteoinductive bioactivity. The purpose of the present study was to develop a polydopamine (pDA)-assisted BMP-2-derived peptide (designated as P24) surface modification strategy for improving the osteogenesis of the nHA/RHLC/PLA scaffold. The immobilization efficiency and release kinetics of P24, and in vitro osteoinductive activity of the nHA/RHLC/PLA-pDA-P24 scaffold were examined. The in vivo osteoinductive activity of the scaffold was evaluated usinga rat criticalsize calvarial defect model. Our results showed that pDA-assisted surface modification could more efficiently mediate the immobilization of P24 peptide onto the scaffold surfaces than physical adsorption. The in vitro release study showed that the P24 peptide was released slowly and steadily from the nHA/RHLC/PLA-pDA-P24 scaffold in a sustained manner, with a short initial burst release only during the first day, while the physisorbed nHA/RHLC/PLA-P24 group showed a sharp burst P24 release followed by a plateau phase. In vitro osteogenesis assay, the ALP activitiy and mRNA expression of osteo-specific markers of rat-derived mesenchymal stem cells (rMSCs) in the nHA/RHLC/PLA-pDA-P24 group were significantly higher than those of the nHA/RHLC/PLA-P24 and non-P24-loaded nHA/RHLC/PLA groups. In vivo, three-dimensional CT evaluation and histological examination demonstrated the nHA/RHLC/PLA-pDA-P24 scaffolds significantly enhanced bone regeneration of rat cranial defects to a much greater extent than physisorbed nHA/RHLC/PLA-P24 and non-P24-loaded nHA/RHLC/PLA scaffolds. Our findings indicated that the pDA-assisted surface modification method could significantly improve the osteogenesis activity of the nHA/RHLC/PLA scaffold and the new nHA/RHLC/PLA-pDA-P24 scaffold was a promising scaffold biomaterial for bone tissue regeneration.