A Sprayable Temperature-Sensitive Hydrogel Promotes Oral Ulcer Healing through NGFR/ERK Signaling Pathway

Oral ulcer is a common oral mucosal injury disease that causes significant inconvenience and discomfort for patients. Traditional treatments, such as drugs, ointments, and patches, have limitations, including low local drug utilization, short residence time on the affected area, and the risk of secondary injury from manual application. To address these issues, this study developed a sprayable temperature-sensitive hydrogel (PEI/PAA/PF127-CHO/AA2G@MSN-NH₂ hydrogel, PMAG) without manual contact on injuryed mucosa by combining aldehyde-modified Pluronic F-127 (PF127-CHO), ascorbic acid 2-glucoside-loaded amino-mesoporous silica (AA2G@MSN-NH₂), polyethylenimine (PEI), and polyacrylic acid (PAA) through Schiff base reaction and physical crosslinking. When sprayed onto an oral ulcer, PMAG exhibits excellent temperature sensitivity and adhesion, rapidly adapting to oral temperature and forming a protective film that closely adheres to the ulcer surface. This creates a stable healing environment by isolating the wound from external stimuli. PMAG has demonstrated significant abilities in promoting epithelial cell proliferation and migration, as well as antioxidant, anti-inflammatory, and antibacterial properties. RNA sequencing revealed that the tissue repair-promoting effects of PMAG are primarily mediated by activating the nerve growth factor receptor/extracellular signal-regulated kinase (NGFR/ERK) signaling pathway. In summary, PMAG represents a significant advancement in improving the treatment of oral ulcers and offers a more convenient option for patients.