Injectable dual-network hydrogel for phototherapy and immunomodulation in the treatment of MRSA-infected and diabetic wound

• Synthesis of a porphyrin-based cationic organic polymer nanoparticle with good PDT and PTT . • A dual-network hydrogel with easy injectability, good antibacterial, controllable release, and good immunoregulation. • Significant wound healing effect on both MRSA-infected and diabetic wounds . Continuous invasion and infection of drug-resistant bacteria leads to chronic inflammation and ulcers in skin wounds, which hinders wound healing and even results in sepsis. Here, we constructed a multifunctional injectable hydrogel (GA/PIOP/SF) that was composed of a synthesized porous ionic organic polymer (PIOP) with photothermal and photodynamic therapy (PDT/PTT) capacities to kill bacteria, a bioactive small molecule glycyrrhizinic acid (GA) to trigger macrophage polarization towards M2-type, and silk fibroin (SF) with excellent biocompatibility to facilitate cell proliferation. In vitro antibacterial and cellular experiments revealed that the GA/PIOP/SF hydrogel exhibited excellent bactericidal activity and induced M2-type macrophage polarization, promoting L929 fibroblast migration. In the methicillin-resistant Staphylococcus aureus (MRSA) infected wound model, GA/PIOP/SF hydrogel created a sterile microenvironment at the wound site by activating the PDT/PTT properties of PIOP through 660 nm laser irradiation, which could destroy the MRSA structure, and combined GA to regulate the immune microenvironment of the wound site. Moreover, in chronic diabetic wound models, the photothermal activity of PIOP promoted the disintegration of self-assembled GA nanofibers. It released the GA small molecules from the GA/PIOP/SF double network, facilitating macrophage polarization from M1-type to M2-type and alleviating inflammation. There two animal experimental results presented that the GA/PIOP/SF hydrogel could accelerate the recovery of both MRSA-infected wound and diabetic wounds through its antibacterial activity and improved fibroblast migration, M2-type macrophage polarization, as well as angiogenesis, demonstrating its excellent application potential as wound dressing in the treatment of chronic infected diabetic wound.