An injectable and photocurable methacrylate-silk fibroin/nano-hydroxyapatite hydrogel for bone regeneration through osteoimmunomodulation

Tissue engineering has emerged as a promising approach for addressing bone defects. Most of the traditional 3D printing materials predominantly relying on polymers and ceramics. Although these materials exhibit superior osteogenic effects, their gradual degradation poses a limitation. Digital light processing (DLP) 3D bioprinting that uses natural biomaterials as bioinks has become one of the promising strategies for bone regeneration. In this study, we introduce a hydrogel biomaterial derived from silk fibroin (SF). Notably, we present the novel integration of nano-hydroxyapatite (nHA) into the hydrogel, forming a composite hydrogel that rapidly cross-links upon initiation. Moreover, we demonstrate the loading of nHA through non-covalent bonds in SilMA. In vitro experiments reveal that composite hydrogel scaffolds with 10 % nHA exhibit enhanced osteogenic effects. Transcriptomic analysis indicates that the composite hydrogel promotes bone regeneration by inducing M2 macrophage polarization. Furthermore, rat femoral defect experiments validate the efficacy of SilMA/nHA10 in bone regeneration. This study synthesis of a simple and effective composite hydrogel bioink for bone regeneration, presenting a novel strategy for the future implementation of digital 3D printing technology in bone tissue engineering.