Integration of chitosan-derived carbon dots and Carbomer hydrogel for sustained antibacterial and immunomodulatory efficacy in treating MRSA-infected diabetic wounds.

Bacterial infection and insufficient angiogenesis caused by immune dysregulation pose significant challenges to diabetic wound healing. Effectively combating bacterial infection and modulating endothelial function through the polarization of M2 macrophages to promote angiogenesis are considered as effective strategies for treating diabetic wounds. However, local treatment that achieves dual effects of antibacterial and immunomodulation through simple pathways remains limited. There is a critical need for the development of a wound dressing that possesses both antimicrobial activity and the ability to modulate the immune response within the wound microenvironment. Herein, the positively charged chitosan-derived carbon dots (CCDs) with excellent antibacterial activity were synthesized by a one-step hydrothermal method, demonstrating significant efficacy against methicillin-resistant Staphylococcus aureus (MRSA). The carbomer hydrogel (CH) was designed for loading CCDs to be the hybrid hydrogel (CCDs@CH). CCDs@CH not only possessed pH responsiveness and enhanced mechanical properties that enabled adaptation to the wound microenvironment, but also exhibited pronounced immunomodulatory and pro-angiogenic activities. In a rat model of MRSA-infected skin wound, CCDs@CH significantly accelerated wound healing, resulting in a healing rate of 72.3 % on day 7 and 98.7 % on day 14. Furthermore, a reduction in bacterial load at the wound site by over 90 % was observed in CCDs@CH group, whose cure was also confirmed by histological examination. This topical hydrogel provides a straightforward and effective approach for treating infectious wounds and offers new insights into treating diabetic wounds.