Carbomol hydrogels integrating chlorogenic acid-loaded exosomes promote diabetic wound healing through antibacterial and immunomodulatory activities.

Diabetic wounds represent a significant global clinical challenge, exacerbated by persistent bacterial infection and a dysregulated inflammatory microenvironment. Effective strategies for diabetic wounds are absent. Here, we found that NOD-like receptor thermal protein domain associated protein 3 (NLRP3) is an important regulating molecule associated with inflammatory microenvironment. We engineered Carbomol hydrogels integrating chlorogenic acid-loaded exosomes (Exo-CA@CB) to address both infection and NLRP3-mediated inflammation. The Carbomol hydrogel (CB) matrix provides biocompatibility, adhesion, self-healing properties, and sustained release, while the encapsulated Exo-CA deliver bioactive cargo. In vitro studies demonstrated the potent antibacterial activity of Exo-CA@CB against common wound pathogens. Crucially, Exo-CA@CB effectively promoted macrophage polarization towards the regenerative M2 phenotype. In the infected diabetic wound model, topical application of Exo-CA@CB hydrogels significantly accelerated healing. This study validates a new approach, initiated by single-cell analysis, for developing Exo-CA@CB hydrogels as a promising platform to manage infected diabetic wounds by concurrently tackling infection and NLRP3-driven inflammation.