Adelmidrol: A novel osteogenic mineralization regulator for bone defect repair via activating the Notch pathway with drug-loaded hydrogel.

Bone defect, irreversible bone loss impairing physiological functions, raises complication risks, lowers life quality and burdens healthcare, demanding effective novel repair strategies. This study aimed to screen candidate drugs promoting osteoblast (OB) osteogenic mineralization for bone defect repair. High-throughput screening identified adelmidrol from a phase 3 clinical drug library. In vitro experiments showed adelmidrol significantly upregulated RUNX2 and OSX expression, enhancing OB osteogenic mineralization by activating the Notch signaling pathway. In vivo, a methacrylated silk fibroin hydrogel scaffold loaded with aminated bioactive glass and adelmidrol (SFMA/GelMA/MBG-NH2-Ad) effectively promoted OB osteogenic mineralization, reduced bone defect area, and repaired mouse critical calvarial defects. In conclusion, this study clarifies adelmidrol's regulatory effect on OB osteogenic mineralization and its molecular mechanism, confirms the scaffold's efficacy in bone defect repair, providing a new candidate drug and experimental basis for clinical bone defect treatment.