Extracellular matrix-inspired natural polymer-based composite hydrogel dressings for infected wound healing

Developing an effective hydrogel dressing to protect against bacterial infection and exhibit synchronously integrated mechanical robustness and self-healing properties is highly desirable for infected wound healing in clinical practice. Inspired by the extracellular matrix (ECM), we constructed a dynamic and nondynamic synergy network to prepare a natural polymer-based composite hydrogel dressing for infected wound healing. The aldehyde groups of oxidized hyaluronic acid were bonded with amino groups of carboxymethyl chitosan and polyacrylamide (PAAm) <i>via</i> the Schiff base reaction to form a dynamic crosslinked network, mimicking the dynamically reversible glycosaminoglycan network in the ECM. A nondynamic PAAm network was created <i>via</i> UV-irradiated free radical polymerization, analogous to the covalently crosslinked collagen network in the ECM. The elaborate dynamic and nondynamic synergy network enabled the resultant hydrogel dressing to exhibit high mechanical strength and fatigue resistance, excellent self-healing properties and the remarkable antibacterial activity. An <i>in vivo Staphylococcus aureus</i>-infected full-thickness wound model revealed that our natural polymer-based composite hydrogel dressing significantly reduced inflammation and promoted the formation of granulation tissues and angiogenesis to achieve accelerated infected wound healing. This study offers a valuable reference for designing and fabricating multifunctional hydrogel dressings for treating wound infection.