Orchestrating diabetic wound healing via a bio-inspired and dual-modal scaffold: integrating photothermal nanozymes and exosome-mediated immunomodulation

Diabetic chronic wounds (DCWs) remain a severe clinical challenge due to their prolonged inflammatory response, impaired tissue repair, high risk of bacterial infection, and limited angiogenesis. To address this, we developed a multifunctional dressing, HA-RHC-AP@MSC-Exo, integrating hyaluronic acid, recombinant human collagen, silver-containing apatite, and mesenchymal stem cell-derived exosomes (MSC-Exo). The dressing exhibits optimal hydrophilicity and degradation rates matching tissue repair. In vitro, it demonstrated potent antibacterial activity against S. aureus and E. coli, augmented by photothermal effects under NIR irradiation. Furthermore, HA-RHC-AP@MSC-Exo promoted the transition of macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes and enhanced fibroblast migration and angiogenesis. In vivo studies in diabetic rat confirmed accelerated wound closure with nearly complete healing by day 15. Histological and transcriptomic analyses revealed enhanced collagen deposition, vascularization, and regulation of key signaling pathways involved in tissue remodeling. Consequently, HA-RHC-AP@MSC-Exo offers a synergistic therapeutic strategy for effective DCW treatment.