Antibacterial composite protein microneedle loaded with hypoxia-treated exosomes for oral ulcer healing

Oral ulcer treatment is challenging: various dressings have been developed, but they have poor efficacy. The efficacy of oral ulcer treatment depends on the local drug concentration; low drug concentrations result in slow wound healing. Therefore, the sustained release of active therapeutic ingredients from wound dressings with few administrations is promising. Hypoxic exosomes (Exos) can promote cell proliferation and angiogenesis. Further, silver nanoparticles (AgNPs) confer broad-spectrum antimicrobial effects. We prepared a light-cured composite microneedle (MN) patch based on bovine serum albumin methacryloyl (BSAMA) and methacrylic gelatin (GelMA) (the combination is denoted BG). Control, BG, BG@Exos, and BG@Exos&AgNPs were used to explore the therapeutic effects of hypoxic Exos and AgNPs on oral ulcers. In vitro experiments showed that BG@Exos&AgNPs MN patches effectively promoted cell migration, proliferation, and angiogenesis and significantly inhibited bacterial growth and expression of IL-2 and TNF-ɑ. We found that BG@Exos&AgNPs promoted the healing of oral ulcers in rats, demonstrated by rapid wound epithelial healing, downregulation of inflammatory factor expression, and increased macrophage polarization. Therefore, the designed BG@Exos&AgNPs MN patch is a valuable approach for treating oral ulcers.