AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4
Wenzhang Liu, Hongchao Huang, Futing Shu, Yingying Liu, Jiezhi Lin, Lu Yang, Wei Zhang, Luofeng Jiang, Tianyi Liu, Chaoran Xie, Lei Li, Yin He, Shichu Xiao, Yongjun Zheng, Zhaofan Xia
Abstract
Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired keratinocyte function, both of which are key factors contributing to delayed healing. In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing. We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues, with detrimental effects on keratinocyte proliferation, migration, and apoptosis. Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4 (OLFM4), a key gene associated with cell proliferation, adhesion and migration. To optimize delivery and therapeutic efficacy, we engineered MSC-derived exosomes loaded with antagomiR-192-5p (ant-192; Final content: 2 nmol per wound; Loading efficiency: 35.22 ± 0.34 %) and then encapsulated into a composite hydrogel composed of GelMA and MXene (Ti 3 C 2 Tx) nanosheets, forming a multifunctional dressing (Exo-ant-192@M-Gel). It achieved sustained release of ant-192, delay its degradation, and exert anti-inflammatory properties, thus promoting epithelization and burn wound healing. This study offered a novel therapeutic approach for burn wound closure.