Multifunctional nanofiber-based dressings in coordination with adipose-derived stem cells for accelerated burn wound healing

• The tri-layered, adipose-derived stem cell-based wound dressing achieves multifunctional burn repair, offering a highly promising solution. • Nanofiber-structured outer layer creates EGF gradient, boosting keratinocyte migration via chemotaxis. • Middle methacrylate-chitosan/gelatin nanofiber layer inhibits E. coli and S. aureus growth. • Nanofiber/adermal inner layer boosts stem cell paracrine function, increasing EGF/FGF secretion to enhance angiogenesis and wound healing. Burn wound healing remains a significant clinical challenge due to infections and poor tissue regeneration. To address this issue, we developed a tri-layered wound dressing (TLWD) integrated with adipose-derived stem cells (ADSCs, TLWDA) to accelerate burn wound repair. The outer layer consists of radially aligned nanofibers coated with a gradient of epidermal growth factor (EGF) to promote epidermal regeneration. The middle layer is composed of dense gelatin nanofibers coated with methacrylate-chitosan hydrogel, providing mechanical support and antimicrobial properties. The inner layer features mesh-structured nanoyarns coated with gelatin nanofibers, which can regulate the paracrine secretion of ADSCs. Antibacterial assay and live/dead bacterial staining confirmed that the TLWDA scaffold exhibits excellent antimicrobial activity. Scratch assays demonstrated that TLWDA enhances the migration of keratinocytes, fibroblasts, and endothelial cells. Additionally, TLWDA markedly improves angiogenesis and upregulates the secretion of EGF and fibroblast growth factor (FGF2) from ADSCs. In vivo experiments, compared to TLWD or ADSCs alone, TLWDA significantly accelerates the healing process of burn wounds, while improving the thickness of the regenerated epidermal layer, collagen deposition, and vascularization. The synergistic effect of this multifunctional nanofiber-based composite scaffold with ADSCs offers a highly promising strategy for the effective repair of burn wounds.