Photothermal-Immunomodulatory Hydrogel Reinforced by Ti3C2/ZnAl-LDH Nanoplatform for Eradicating MRSA and Promoting Diabetic Wound Healing.

MRSA infections give rise to chronic cutaneous and advance into profound tissue invasions, including osteomyelitis and sepsis-conditions for which existing clinical interventions offer only limited efficacy. The utility of broad-spectrum antibiotics has become increasingly compromised by escalating drug resistance, inadequate tissue targeting, and deleterious side effects. Neutrophil extracellular traps (NETs) have emerged as a compelling immunotherapeutic avenue for eradicating multidrug-resistant pathogens. Inspired by the bactericidal and immunoregulatory functions of NETs, we developed a photothermal-immunomodulatory hydrogel reinforced by a Ti3C2/ZnAl-LDH nanoplatform to mimic NETs-like antimicrobial defense while overcoming their inherent limitations. Hollow photothermal nanoparticles were fabricated from 2D Ti3C2 and ZnAl-LDH (TiZ) nanosheets and infused with chlorogenic acid, forming CTiZ. These were cloaked in membranes derived from apoptotic neutrophils to create a NETs-mimetic functional bacterial trapper (CTiZM), which was then encapsulated within a thermoresponsive dopa-poly(N-isopropylacrylamide) hydrogel (dopa-PNIPAm, DP), yielding a composite hydrogel system designated CTiZM@DP. This sophisticated platform amplifies antibacterial potency through effective microbial entrapment and the generation of reactive oxygen species, while simultaneously orchestrating the polarization of macrophages toward a reparative M2 phenotype under the influence of gentle photothermal stimulation. Collectively, this integrative strategy heralds a promising therapeutic modality for the eradication of multidrug-resistant infections and the enhancement of wound healing in individuals with diabetes.