Sodium alginate oxide/methacrylic anhydride gelatin dual network nano-enzymatic hydrogel promotes bone repair by modulating the microenvironment

• Hydrogel exhibits both ZIF-8/Fe-based enzyme-like activity and TAX sustained-release functionality. • Dual-network nanozyme hydrogel efficiently scavenges ROS and inhibits bacterial biofilm formation. • Dual-network nanozyme hydrogel synergistically modulates the bone repair microenvironment by activating the PI3K/AKT pathway. Bone defects caused by disease or trauma pose significant challenges for clinical treatment, necessitating the development of innovative therapeutic agents to promote bone repair. Currently, in hydrogel systems used to treat bone defects, drug release rates are relatively fast and fail to balance the microenvironment following bone defect formation, thereby failing to achieve optimal bone repair outcomes. A dual-network hydrogel composed of methyl acrylate gelatin and sodium alginate loaded with Taxifolin was obtained through UV curing technology and applied to tibial defects. Experimental results showed that the Zeolitic Imidazolate Framework-8/Fe@Taxifolin (ZIF-8/Fe@TAX) hydrogel not only exhibited excellent peroxidase (POD) activity and catalase (CAT) activity but also demonstrated stable, sustained-release effects and inhibited the formation and proliferation of bacterial biofilms, thereby reducing the risk of infection. Transcriptomic analysis indicated that bone defect formation is associated with the activation of the PI3K/AKT signalling pathway. In vivo experiments confirmed that this composite hydrogel activates the pathway, significantly upregulating osteopontin expression in rat tibial tissue, thereby accelerating bone defect repair. In summary, this composite hydrogel provides a theoretical basis and a highly promising candidate material for bone defect repair.