Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients

• DOI: 10.1016/j.xcrm.2024.101588
• Publication Date: 2024-05-22T14:31:16Z
• Authors: Jing Xie; Xuhua Liu; Biaoliang Wu; Bochong Chen; Qiancheng Song; Yuan Guan; Yuanxun Gong; Chengliang Yang; Jinbo Lin; Mingfeng Huang; Xinyu Tan; Ruijun Lai; Xiaozhen Lin; Sheng Zhang; Xiaoling Xie; Xiaoli Chen; Chunyuan Zhang; Mei Yang; Huijiao Nong; Xiaoyang Zhao; Laixin Xia; Weijie Zhou; Guozhi Xiao; Qing Jiang; Weiguo Zou; Di Chen; Di Lu; Jia Liu; Xiaochun Bai
• Keywords: Regenerative Medicine

Tibial cortex transverse distraction is a surgical method for treating severe diabetic foot ulcers (DFUs), but the underlying mechanism unclear. We show that antioxidant proteins and small extracellular vesicles (sEVs) with multiple-tissue regenerative potential are released during bone transport (BT) in humans rats. These accumulate wounds enriched microRNAs (miRNAs) (e.g., miR-494-3p) have high activities improve circulation of ischemic lower limbs while also promoting neovascularization, fibroblast migration, nerve fiber regeneration. Deletion miR-494-3p rats reduces beneficial effects BT on wounds, hydrogels containing reduced glutathione (GSH) effectively repair them. Importantly, ginsenoside Rg1 can upregulate miR-494-3p, randomized controlled trial verifies regimen oral GSH accelerates wound healing refractory DFU patients. findings identify functional factors tissue regeneration suggest therapy DFUs.