A Bio‐Responsive Hydrogel with Spatially Heterogeneous Structure for Treating Infectious Tissue Injuries

Abstract Infectious tissue injuries, exacerbated by bacterial infections and antibiotic resistance, pose significant challenges for treatment and may lead to life‐threatening systemic infections. In this study, a bio‐responsive hydrogel system is developed, leveraging silver ions (Ag⁺) encapsulated in Preyssler‐type polyoxometalates (POMs). The Ag⁺ ions are selectively released in response to endogenous sodium ions (Na⁺) within the biological environment, enabling broad‐spectrum antibacterial activity. The POM serves as a protective matrix for Ag⁺, preserving its bioactivity while mitigating cytotoxicity and the reduction in antimicrobial efficacy associated with prolonged exposure. Additionally, a dual‐channel technique is employed to fabricate fiber membranes with controllable and continuously stacked chemical compositions, ensuring efficient and uniform POM incorporation via hydrogen bonding within the fiber matrix. Subsequently, in situ hierarchical cross‐linking process generated a spatially heterogeneous hydrogel with an interpenetrating network structure at multiple scales. This differentiated microstructure facilitates the controlled loading and release of diverse therapeutic components. Meanwhile, bioactive exosomes are integrated into the hydrogel, further enhancing its regenerative potential for treating infectious tissue injuries. In vitro and in vivo experiments demonstrated that the advanced hydrogel system provide a viable and efficient platform for addressing the challenges associated with infectious tissue injuries, offering a promising strategy for clinical applications.