Spatiotemporally responsive hybrid hydrogels for sequential therapy and visualized monitoring of multidrug-resistant bacterial wound infections.

Abstract

Infectious wounds pose a persistent clinical challenge, further aggravated by the rising prevalence of antibiotic-resistant pathogens, which significantly impair therapeutic efficacy and patient prognosis. Addressing the pressing need for effective interventions against multidrug-resistant (MDR) bacterial infections necessitates the development of next-generation therapeutic platforms capable of simultaneously achieving infection control, immune modulation, tissue regeneration, and real-time therapeutic monitoring. Herein, we report the rational design of an A-π-D-π-A conjugated hybrid photosensitizer (TPAB-Cu²⁺) with potent photodynamic antibacterial activity and fluorescence responsiveness to the infectious microenvironment. By incorporating natural herbal emodin and modified hyaluronic acid, a spatiotemporally responsive hybrid hydrogel (EM@mHA-TPAB-Cu²⁺) is fabricated via dynamic Schiff base crosslinking. Upon light activation, the hydrogel generates abundant reactive oxygen species (ROS), enabling efficient eradication of MDR bacteria and disruption of mature biofilms. Moreover, the sustained release of emodin scavenges excessive ROS and reprograms the immune microenvironment, thereby facilitating the transition from inflammation to cellular proliferation and tissue remodeling. In vivo studies confirm that this intelligent hydrogel effectively eliminates MDR bacteria, mitigates inflammation, accelerates tissue regeneration, and enables real-time fluorescence monitoring of the therapeutic process. This spatiotemporally responsive hydrogel dressing system, integrating therapeutic and monitoring capabilities, offers significant promise for advanced management of infected wounds.