The repair of large bone defects remains a challenging problem in bone tissue engineering. Ischemia and hypoxia in the bone defect area make it difficult for seed cells to survive and differentiate, which fail to perform effective tissue regeneration. Current oxygen-producing materials frequently encounter problems such as a rapid degradation rate, insufficient mechanical properties, difficult molding, and cumbersome fabrication. Here, a novel three-dimensional (3D) printed integrated bionic oxygenated scaffold was fabricated with gelatin-CaO2 microspheres, polycaprolactone (PCL), and nanohydroxyapatite (nHA) using low-temperature molding 3D printing technology. The scaffold had outstanding mechanical properties with bionic hierarchical porous structures. In vitro reports showed that the scaffold exhibited excellent cytocompatibility and could release O2 sustainably for more than 2 weeks, which significantly enhanced the survival, growth, and osteogenic differentiation of bone marrow mesenchymal stem cells under hypoxia. In vivo experiments revealed that the scaffold facilitated efficient bone repair after it was transplanted into a rabbit calvarial defect model. This result may be due to the scaffolds reducing hypoxia-inducible factor-1α accumulation, improving the expression of osteogenic regulatory transcription factors, and accelerating osteogenesis. In summary, the integrated bionic PCL/nHA/CaO2 scaffold had excellent capabilities in sustainable O2 release and bone regeneration, which provided a promising clinical strategy for bone defect repair.
Keywords: 3D printed scaffolds; bone regeneration; hypoxia; large bone defects; oxygenated.