Diabetic chronic wounds heal slowly due to persistent inflammation, impaired macrophage polarization, and compromised angiogenesis, while conventional therapies fail to effectively modulate the wound microenvironment. This study aimed to develop pagoda-like microneedle (MN) patches incorporating isoliquiritigenin (ISL)-loaded hollow mesoporous copper sulfide nanoparticles (HMCuS@ISL MNs) with near-infrared (NIR) photothermal functionality to achieve local immunometabolic regulation and promote angiogenesis, antibacterial activity, and wound repair. HMCuS@ISL nanoparticles were integrated into a collagen/hyaluronic acid matrix to form pagoda-like MN patches. Nanoparticles were characterized by TEM, DLS, and UV–vis–NIR spectroscopy, and their photothermal performance under 808 nm irradiation was evaluated. MN mechanical strength, dissolution, cytocompatibility, antibacterial activity, and in vitro angiogenesis were systematically assessed. ISL-mediated macrophage polarization was analyzed via RNA sequencing, qPCR, flow cytometry, and metabolic flux assays. In vivo efficacy and biosafety were evaluated in streptozotocin-induced diabetic mouse wound models. HMCuS@ISL nanoparticles displayed uniform hollow–mesoporous morphology with strong NIR absorption and efficient photothermal conversion. MN patches exhibited excellent mechanical strength, rapid dissolution, and good biocompatibility. ISL promoted M2 macrophage polarization by suppressing glycolysis and enhancing fatty acid oxidation. HMCuS@ISL MNs, especially under NIR irradiation, significantly enhanced fibroblast migration, angiogenesis, antibacterial activity, and accelerated wound closure. Histological and immunostaining analyses confirmed improved re-epithelialization, collagen deposition, vascularization, and immune microenvironment balance without systemic toxicity. HMCuS@ISL MN patches integrating metabolic immune modulation with photothermal therapy provide an effective, safe, and minimally invasive strategy for diabetic wound healing.
Liu et al. (Wed,) studied this question.