The Extracellular Matrix Promotes Diabetic Oral Wound Healing by Modulating the Microenvironment

Oral wounds in diabetes mellitus (DM) often delay healing due to reduced angiogenesis and increased inflammatory response in the local microenvironment, even leading to graft necrosis and implant failure. Therefore, developing an effective program to promote healing is of great clinical value. Much of the current research is focused on promoting wound healing through surface adhesive materials that exert a pro-angiogenic, anti-inflammatory effect. However, the application of surface bonding materials in the oral cavity is very limited due to the humid and friction-prone environment. Decellularized extracellular adipose tissue (DAT) is an easily accessible and biocompatible material derived from adipose tissue. To further explore the potential of DAT, we used multi-omics to analyze its composition and possible mechanisms. Proteomic studies revealed that DAT contains anti-inflammatory, pro-angiogenic proteins that promote DM tissue regeneration. To adapt to the moist and chewing friction environment of the mouth, we modified DAT into a temperature-sensitive hydrogel material that can be injected intramucosally. DAT hydrogel has been verified to promote angiogenesis and exert anti-inflammatory effects through macrophage phenotypic transformation. Meanwhile, transcriptome analysis suggested that the inhibitory effect of DAT on the interleukin 17 signaling pathway might be a key factor in promoting DM oral wound healing. In conclusion, after multi-omic analysis, DAT hydrogel can exert good pro-angiogenic and anti-inflammatory effects through the interleukin 17 signaling pathway and can be adapted to the specific environment of the oral cavity. This provides a potential way to promote DM oral wound healing in a clinical setting.