HAMA microneedles patch loaded with Three-Dimensional exosome and Mupirocin promote diabetic wound healing.

Diabetic wound healing impairment poses significant clinical challenges due to infection risks, poor angiogenesis, and chronic inflammation, often leading to amputation or death. Recently, mesenchymal stem cell-derived exosomes (Exos) exhibit potential in enhancing angiogenesis and suppressing inflammation, yet clinical application is limited by short half-life, low bioavailability, and high costs. Three-dimensional (3D) culture technology improves exosome yield and therapeutic efficacy, demonstrating superior performance in tissue regeneration. Concurrently, microneedle (MN) systems enable efficient transdermal drug delivery with minimal invasiveness. This study integrates 3d-Exo with Mupirocin into a hyaluronic acid methacrylate (HAMA)-based MN patch (3d-Exo MN) to enhance diabetic wound healing. The HAMA matrix ensures exosome stability and controlled release, while Mupirocin targets infection. In vitro and in vivo evaluations reveal that 3d-Exo MN significantly promotes cell proliferation, migration, and neovascularization, addressing key limitations of conventional therapies. By synergizing 3d-Exo advantages with MN-mediated delivery, this innovative platform offers a targeted, biocompatible strategy for diabetic wound management, bridging gaps in current treatment paradigms through enhanced drug efficacy and localized action.