Abstract

Treating bone defects complicated by bacterial infections remains a significant clinical challenge. Drawing inspiration from the human body’s bone repair mechanisms, the use of biomimetic methods to design tissue engineering scaffolds is 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 hydrogel achieves multi-modal bone tissue biomimicry: (i) GelMA/gelatin mimics the matrix components in bone ECM, ensuring biocompatibility 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 structural and mechanical biomimicry to provide necessary support for bone defects; (iii) The elemental biomimicry of Si and Cu in Cu@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 that the 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 and vivo 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-regulating properties can serve as a multifunctional scaffold, offering antimicrobial properties for infected bone regeneration, and guide for future research in bone regeneration and three-dimensional printing.