Self-healing quaternized chitosan-phenylboronic hydrogel with ceria nanozymes and stem-cell exosomes simultaneously eradicates MRSA biofilm and regenerates diabetic wounds.

Diabetic wounds represent a major clinical challenge due to their susceptibility to bacterial biofilm infections, persistent oxidative stress, and impaired tissue regeneration. Current therapeutic approaches typically address these pathological factors individually, limiting their overall efficacy in achieving complete wound closure. There is thus an urgent need for integrated platforms capable of simultaneously targeting multiple barriers to healing. Here we show that a self-healing hydrogel composed of quaternized chitosan-phenylboronic acid (QCSP), ceria nanoparticles (CeNPs), and embryonic stem cell-derived exosomes (ESC-Exo) effectively eradicates methicillin-resistant Staphylococcus aureus (MRSA) biofilms, scavenges reactive oxygen species, and promotes tissue regeneration in diabetic mice. The QCSP matrix provides inherent antibacterial activity and injectable, self-healing properties, while CeNPs function as catalytic antioxidants through reversible Ce3+/Ce4+ redox cycling. Incorporation of ESC-Exo further enhances angiogenesis and re-epithelialization. In an MRSA-infected diabetic wound model, this multifunctional hydrogel achieves near-complete wound closure within 12 days alongside significant biofilm clearance and collagen deposition. This work demonstrates that integrating natural polymer-based hydrogels with nanozymes and bioactive exosomes offers a promising strategy for managing complex chronic wounds.