Injective Programmable Proanthocyanidin‐Coordinated Zinc‐Based Composite Hydrogel for Infected Bone Repair

Abstract Effectively integrating infection control and osteogenesis to promote infected bone repair is challenging. Herein, injective programmable proanthocyanidin (PC)‐coordinated zinc‐based composite hydrogels (ipPZCHs) are developed by compositing antimicrobial and antioxidant PC‐coordinated zinc oxide (ZnO) microspheres with thioether‐grafted sodium alginate (TSA), followed by calcium chloride (CaCl 2 ) crosslinking. Responsive to the high endogenous reactive oxygen species (ROS) microenvironment in infected bone defects, the hydrophilicity of TSA can be significantly improved, to trigger the disintegration of ipPZCHs and the fast release of PC‐coordinated ZnOs. This together with the easily dissociable PC‐Zn 2+ coordination induced fast release of antimicrobial zinc (Zn 2+ ) with/without silver (Ag + ) ions from PC‐coordinated ZnOs (for Zn 2+ , > 100 times that of pure ZnO) guarantees the strong antimicrobial activity of ipPZCHs. The exogenous ROS generated by ZnO and silver nanoparticles during the antimicrobial process further speeds up the disintegration of ipPZCHs, augmenting the antimicrobial efficacy. At the same time, ROS‐responsive degradation/disintegration of ipPZCHs vacates space for bone ingrowth. The concurrently released strong antioxidant PC scavenges excess ROS thus enhances the immunomodulatory (in promoting the anti‐inflammatory phenotype (M2) polarization of macrophages) and osteoinductive properties of Zn 2+ , thus the infected bone repair is effectively promoted via the aforementioned programmable and self‐adaptive processes.