Abstract: Treating bone defects complicated by bacterial infections remains a significant clinical challenge. Drawing inspirationfrom the human body’s bone repair mechanisms, the use of biomimetic methods to design tissue engineering scaffoldsis of great significance for bone repair. This study synthesized copper (Cu)-doped mesoporous silica nanoparticles (Cu@MSN) modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN (Cu@MSNMA). Furtheremore, biomimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution. This hydrogelachieves multi-modal bone tissue biomimicry: (i) GelMA/gelatin mimics the matrix components in bone ECM, ensuringbiocompatibility while promoting cellular behavior (such as adhesion, proliferation, and differentiation); (ii) GelMA/gelatin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure, achieving structuraland mechanical biomimicry to provide necessary support for bone defects; (iii) The elemental biomimicry of Si and Cu inCu@MSNMA achieves efficient osteogenic induction. The effect of different proportions of Cu@MSNMA on the physical properties of the composite hydrogels was investigated to determine the optimal proportion. The results indicated thatthe mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio. Notably, 5% NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel. In vitro andvivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition. In conclusion, the proposed nanocomposite hydrogel with biomimetic components and ion-regulatingproperties can serve as a multifunctional scaffold, offering antimicrobial properties for infected bone regeneration, andguide for future research in bone regeneration and three-dimensional printing.

Key words: Bone defect repair, Methacrylated gelatin, Copper-doped mesoporous silica nanoparticles, Bionicstrategy, Bone tissue engineering')">Bone defect repair, Methacrylated gelatin, Copper-doped mesoporous silica nanoparticles, Bionicstrategy, Bone tissue engineering