Physiologically Responsive Nanocomposite Hydrogel for Integrative Antibacterial Therapy and Wound Regeneration via Cascaded Photothermal-Chemodynamic-Gas Therapy

Bacterial inhibition and tissue regeneration are two crucial challenges for infected wound healing. Herein, a biodegradable sodium alginate/hyaluronic acid hydrogel loaded with functional PSF NPs (Fe²⁺ and S-nitrosothiol co-modified polydopamine nanoparticles) is fabricated to perform integration of antibacterial activities and tissue regeneration promotion via cascaded photothermal-chemodynamic-gas therapy. After application, HS@PSF hydrogel is gradually decomposed in an infected environment with acidic and abundant hyaluronidase (HAase) via Schiff base cleavage and enzymatic hydrolysis to release the PSF NPs. Then the Fe²⁺ in these nanoparticles rapidly converts hydrogen peroxide at infected wound sites into hydroxyl radical via the Fenton reaction to achieve chemodynamic antibacterial therapy. Moreover, this process is significantly promoted by the excellent redox capacity of PDA, which continuously facilitates Fe³⁺ to Fe²⁺ to reproduce the catalysts. In addition, PDA serves as a photothermal agent to achieve anti-bacterial photothermal therapy under near infrared (NIR) irradiation. Notably, NIR irradiation further triggers the cleavage of S-nitrosothiol (SNO) on PSF nanoparticles, causing on-demand NO release at wound sites to inhibit inflammatory and promote tissue regeneration. Both in vitro and in vivo studies demonstrates that HS@PSF hydrogel exerted excellent antibacterial, anti-inflammatory, and pro-angiogenic activities to eliminate infection and promote skin regeneration, providing a promising strategy for infected wound treatment.