Antibacterial, adhesive, and MSC exosomes encapsulated microneedles with spatio-temporal variation functions for diabetic wound healing

Chronic wounds affect healthcare systems and increase the risk of infection. Despite the clinical demand for improving healing, an effective and safe therapeutic approach is still lacking. Here, we present a novel spatio-temporal-varying adhesive microneedle (MN) patch encapsulated with mesenchymal stem cell-derived exosomes (MSC-exos) and antibacterial Ag nanoparticles (AgNPs) for improving wound healing. This MN patch is fabricated by replicating a predesigned flexible template. Consisting of porous methacrylate gelatin hydrogels, the MN tips can continuously deliver anti-inflammatory and pro-angiogenic MSC-exos to wound beds, which can accelerate healing by improving cell functions, remodeling blood vessels and restoring immune systems. Besides, the silk-fibroin-composed MN back enables the patch to stick to the skin well and fix at the wounded site, thus avoiding secondary bandage. By incorporating AgNPs in the MN back, the MN patch is endowed with the ability to efficiently resist microbial contamination and further benefits wound repair. Such a composite MN patch performs well in relieving inflammation, promoting angiogenesis, and suppressing wound-infecting bacteria during wound injury in diabetic rats, with no adverse effects observed. All the features make this multifunctional MN patch potentially valuable for clinical applications. • MSC-exos therapy show encouraging potential in diabetic wound treatment, but is hampered by insufficient delivery. • A novel spatio-temporal-varying adhesive microneedle patch that combines the advantages of MSC-exos and antibacterial AgNPs for improving wound healing. • Efficiency tissue repair and bacteria killing were achieved by the proposed MN patch.