3D printed topologically adjustable oxygen-supply scaffolds for angiogenesis and bone regeneration

Abstract

Degradation of Silk fibroin (SF) provides essential nutrients such as amino acids and peptides for cell proliferation, but cannot provide a slow and sustained O₂ release for osteoblastogenesis, which limits the bone repair effects. For the fabrication of highly personalized and complex bone repair scaffolds, 3D printing technology acts as a tailored tool for the clinical challenge. Therefore, we designed a SilMA/XLG/CaO₂ scaffold system for O₂ supply, which consists of modified photo-crosslinking SF (SilMA), lithium magnesium silicate (XLG) and CaO₂. The combination of modified SF (SilMA) and lithium magnesium silicate (XLG) improves the printability and topological controllability, promoting vascularization and osteogenesis differentiation. Besides, the multi-dimensional modification of CaO₂ enhances the mechanical properties of the scaffolds as well as the adjustability of the O₂ release, providing favorable conditions for osteoblastogenesis. Most importantly, the topology and oxygen release of the 3D printed scaffolds synergistically induced neovascularization and osteoblast differentiation with Mg²⁺ generated by scaffold degradation. Mechanistically, SilMA/XLG/CaO₂ upregulates of angiogenic factors VEGF, CD31, and key osteogenesis proteins RUNX2 and BMP-2, resulting in collagen production and calcium deposition. Overall, our study provides a new strategy for bioactive scaffold preparation that exhibits significant clinical potentials for complex bone defects.