Abstract
Diabetic wounds, particularly combined with pressure ulcers, pose significant therapeutic challenges due to their complex pathophysiology. Conventional treatment strategies often fail to adequately address the multifactorial impairment of healing in these conditions. Here, we proposed and investigated a combinatory strategy employing human adipose-derived mesenchymal stem cell-derived exosomes (hADSC-Exos) with near-infrared-II (NIR-II)-responsive selenium telluride (TeSe) nanoparticle-mediated photothermal therapy (PTT). A full-thickness skin defect pressure ulcer model in diabetic mice was established to systematically evaluate different exosome administration regimens (single high-dose vs. multiple low-dose injections) and their combination effect with TeSe nanoparticle and NIR-II irradiation. We find that multiple low-dose subepidermal injections of hADSC-Exos resulted in more pronounced healing compared to a single high-dose strategy. The combination of low-dose exosomes with TeSe+NIR-II PTT markedly enhanced wound closure quality and stimulated hair follicle regeneration within 21 days. In vitro, TeSe nanoparticles demonstrated effective NIR-II photothermal conversion and antibacterial activity. Their integration with exosomes significantly boosted fibroblast migration and proliferation. Histological analysis confirmed that the combined therapy potently promoted angiogenesis (increased CD31 expression), reduced inflammation (decreased CD68 expression), and improved collagen remodeling (lowered collagen I/III ratio). This work presents an innovative therapeutic approach that synergizes bioactive exosome delivery with microenvironment modulation via antibacterial photothermal therapy, offering a promising prospective treatment for diabetic pressure ulcers.