SCHEDULED MAINTENANCE
Nanohydroxyapatite/polyamide 66 crosslinked with QK and BMP-2-derived peptide prevented femur nonunion in rats
†*ab
and
Jinglong
Yan
†*a
Abstract
Active interventions should be made to avoid delayed bone union and nonunion during fracture treatment. Nanohydroxyapatite/polyamide 66 (nHA/PA66), a simulated bioactive bone substitute with great biocompatibility and mechanical properties, has been widely used in bone regeneration. However, the limited bioactivity of nHA/PA66 has impeded its further application in tissue engineering. In this study, BMP-2-derived peptide and QK (a VEGF mimetic peptide) were dually grafted to PA66 polymer chains to prepare peptide-decorated HA/PA66-BMP-2-QK scaffolds to enhance bone formation after severe femoral fracture (periosteum scraped off) in SD rats. Fourier transform infrared spectroscopy (FTIR) confirmed that the BMP-2-derived peptide and QK were covalently bonded onto the surface of nHA/PA66. In vitro, BMP-2- and QK-modified scaffolds promoted the adhesion and proliferation ability of rBMSCs. After loading onto peptide-modified scaffolds, both BMP2-derived peptide and QK showed sustainable release and preserved bioactivity, improving the osteogenic differentiation ability of BMSCs. The combined ability of these factors to promote osteogenicity was better than that of a single peptide. Furthermore, the QK released from nHA/PA66-BMP-2-QK scaffolds improved the proliferation and tube formation ability of HUVECs. In vivo, femur nonunion in SD rats was successfully prevented by implanting HA/PA66-BMP-2-QK scaffolds into the fracture gap: the fracture line disappeared, the cortical bone showed continuity, the scaffolds were completely embedded and more vessels formed in the nonunion area than observed in other groups. Overall, the nHA/PA66-BMP-2-QK scaffolds simultaneously facilitated angiogenesis and osteogenesis, providing a promising method for reinforcing bone regeneration in nonunion treatment.
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