Polyhexamethylene guanidine derived carbon dots with antibacterial and immunoregulatory properties loaded on carboxymethyl chitosan and ε-poly-L-lysine hydrogel to achieve sustained drug release for treating Pseudomonas aeruginosa infected wound

The treatment of infectious wounds is confronted with the challenges of antibiotic-resistant bacterial infections and excessive inflammatory responses, significantly impacting the healing process. A multifunctional hydrogel dressing system used as local strategy is needed to address this clinical dilemma. Herein, a kind of carbon dots (P-CDs) were synthesized using polyhexamethylene guanidine (PHMG) and citric acid (CA) through a hydrothermal method, exhibiting excellent broad-spectrum antibacterial activity, including effective inhibition of clinically isolated resistant bacteria. The antibacterial mechanism of P-CDs involved the generation of reactive oxygen species, inhibition of ATP synthesis, and disruption of bacterial membrane integrity with the leakage of protein. Additionally, P-CDs demonstrate pronounced immunomodulatory properties by inducing macrophage polarization toward the M2 phenotype, thus modulating the inflammatory microenvironment. These functional components were incorporated into an intelligent hydrogel system (P-CDs@EPCS) constructed from ε-poly-L-lysine and carboxymethyl chitosan, resulting in a wound dressing with tissue adhesion, resilient maintenance of mechanical integrity, and favorable mechanical properties. P-CDs@EPCS exhibited a sustained pH-responsive drug release profile for up to 10 days, maintaining the stability of active constituents throughout the release period. <i>In vivo</i> experiments confirmed that P-CDs@EPCS significantly accelerated wound healing in infections caused by <i>Pseudomonas aeruginosa</i>, demonstrating a synergistic effect of antibacterial, anti-inflammatory, and repair-promoting actions. This study provides a promising solution for treating infectious wounds, integrating key advancements in the field of hydrogels, including dynamic crosslinking design and smart drug delivery systems.