Multi-modular responsive hydroxypropyl chitosan-based hydrogel microspheres for stage-specific therapy in infected wounds.

Dysregulation between bacterial clearance and inflammation regulation leads to delayed healing of infected wounds. Conventional dressings lack the dynamic regulatory capacity and microscale shape adaptability to address this issue. Here, we developed core-shell hydrogel microspheres (HEA@AgM) based on hydroxypropyl chitosan via droplet microfluidics and electrostatic self-assembly. The system achieves stage-specific therapy by integrating a glutathione-responsive antibacterial shell and a ROS-responsive epigallocatechin gallate (EGCG)-loaded core. HEA@AgM precisely conforms to the shape of the wound and degrades in situ in response to ROS, reducing traumatic dressing removal. Microscale spatial compartmentalization enables the accurate release of therapeutic agents in response to different biochemical signals, accomplishing a dual-functional synergy of rapid infection control and sustained immunomodulation. It achieved rapid antibacterial activity (99.6% and 99.8% killing against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and 94.1% biofilm clearance against S. aureus) and sustained antioxidant regulation (DPPH scavenging efficiency of 87.9%), translating into anti-inflammatory efficacy. Hence, it efficiently reduced bacterial burden, suppressed inflammation, promoted tissue repair, and enhanced healing quality in a full-thickness methicillin-resistant S. aureus-infected wound model (70.9% residual area by Day 7). This multifunctional, environment-adaptive system provides guidance and support for developing adaptive wound healing and in situ biodegradable dressings.