Immunomodulatory Sr2+-crosslinked hydrogel with antibacterial, antioxidant, and anti-inflammatory activities for accelerated skin wound healing

• Sr 2+ -crosslinked alginate/carboxymethyl chitosan-based hydrogel promotes skin wound healing. • The hydrogel effectively induces macrophage polarization towards M2 phenotype. • The hydrogel exhibits excellent antibacterial and radical scavenging properties. • The hydrogel suppresses inflammation, promotes angiogenesis, and re-epithelization. Bacterial infection and persistent inflammation significantly impair skin wound healing. To address these problems, a multifunctional hydrogel biomaterial featuring immunomodulatory characteristics is desirable in wound management. Here, an M2 macrophage-polarized hydrogel exhibiting antibacterial, antioxidant, and anti-inflammatory functions was fabricated by simply mixing sodium alginate, carboxymethyl chitosan, 4-formylphenylboronic acid, naringin, and Sr 2+ . Sr 2+ and naringin are effectively loaded into gel networks via coordination reactions and borate esters, respectively. Carboxymethyl chitosan and naringin endowed the hydrogel with excellent antibacterial properties. Naringin also effectively scavenges radicals, thus alleviating oxidative stress. The hydrogel also promotes the reprogramming of macrophages from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory), collectively downregulating the level of pro-inflammatory TNF-α and MPO and upregulates anti-inflammatory IL-10 levels. Additionally, the hydrogel exhibits appropriate mechanical, tissue adhesive, and hemostatic properties. In view of combined therapeutic effects including killing bacteria, scavenging radicals, and macrophage polarization, the hydrogel can alleviate inflammation, promote angiogenesis, and collagen deposition, thereby promoting cutaneous repair in a murine full-thickness excisional wound model. It provides an innovative strategy to facilely prepare multifunctional hydrogel dressing materials with immunomodulatory properties for treating other complex wounds.