Cyclodextrin-based self-assembling hydrogel for Photothermal-controlled nitric oxide release in stage-specific treatment of MRSA-induced arthritis.

MRSA-induced arthritis is a prevalent and highly debilitating orthopedic condition. The inflammatory response induced by bacterial infection hinders tissue repair and exacerbates bone loss. Traditional antibiotic therapies are limited by low bioavailability, substantial side effects, and narrow efficacy, rendering them inadequate for comprehensive treatment of arthritis. Nitric oxide (NO) has demonstrated considerable potential in overcoming bacterial resistance, modulating immune responses, and facilitating tissue repair. Therefore, a stage-specific NO release strategy, tailored to the distinct phases of bacterial arthritis, is essential for effective treatment. In this study, mesoporous polydopamine nanoparticles were utilized as NO donors (mPDA/NONOate) and encapsulated within a supramolecular hydrogel formed via the host-guest interaction between α-cyclodextrin (α-CD) and Pluronic F127. The injectable nature of the resulting NO/PDA-Gel hydrogel ensured uniform distribution within irregular bone joint infection sites, minimizing NO donor loss and enhancing local bioavailability. Notably, upon near-infrared (NIR) irradiation, the hydrogel induces a rapid increase in local temperature, facilitating rapid NO release. At the same time, the synergistic photothermal effect effectively kills bacteria and rapidly controls the infection. Without light irradiation, NO is sustainably and stably released from the NO/PDA-Gel, modulating the bone immune microenvironment, alleviating inflammation, promoting chondrocyte proliferation and differentiation, and accelerating bone tissue repair, thus significantly shortening the healing time of MRSA-induced arthritis. In conclusion, the injectable self-assembled NO/PDA-Gel offers a precise, stage-matched therapeutic approach for MRSA-induced arthritis and holds promise for the treatment of deep-seated infections caused by other multidrug-resistant pathogens.