A novel, three-dimensional, porous, human-like collagen (HLC)/nano-hydroxyapatite (n-HA) scaffold cross-linked by 1,2,7,8-diepoxyoctane (DEO) was successfully fabricated, which showed excellent mechanical and superior biological properties for bone tissue regeneration in this study. The physicochemical characterizations of different n-HA/HLC/DEO (nHD) scaffolds were investigated by determining the morphology, compression stress, elastic modulus, Young’s modulus and enzymatic hydrolysis behavior in vitro. The results demonstrated that nHD-2 and nHD-3 scaffolds showed superior mechanical properties and resistance to enzymatic hydrolysis compared to nHD-1 scaffolds. The cell viability, live cell staining and cell adhesion analysis results demonstrated that nHD-2 scaffolds exhibited low cytotoxicity and excellent cytocompatibility compared with nHD-1 and nHD-3 scaffolds. Furthermore, subcutaneous injections of nHD-2 scaffolds in rabbits produced superior anti-biodegradation effects and histocompatibility compared with injections of nHD-1 and nHD-3 scaffolds after 1, 2 and 4 weeks. In addition, the repair of bone defects in rabbits demonstrated that nHD-2 scaffolds presented an improved ability for guided bone regeneration and reconstruction compared to commercially available bone scaffold composite hydroxyapatite/collagen (HC). Collectively, the results show that nHD-2 scaffolds show promise for application in bone tissue engineering due to their excellent mechanical properties, anti-biodegradation, anti-biodegradation, biocompatibility and bone repair effects.
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