iProXProteomicsRui GuoHomo Sapienshttp://www.iprox.org/page/project.html?id=IPX0013054000rguo@hbu.edu.cnHebei UniversityiProXfalseCathepsin K inhibitor and hUMSC-EVs synergistically promote diabetic wound healing by suppressing ferroptosisRefractory chronic diabetic wounds severely threaten patient survival, yet current treatments fail to adequately promote healing or prevent amputations. Cathepsin K (CTSK), a collagen-degrading protease upregulated in early diabetic wounds, presents a potential therapeutic target, while human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUMSC-EVs) show promise in regeneration but are limited by high costs and instability. This study hypothesizes that combining a stable, cost-effective CTSK inhibitor with hUMSC-EVs could enhance therapeutic efficacy and overcome these challenges. The hypothesis was tested using diabetic wound models in db/db mice and high glucose-exposed human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). The combination of CTSK inhibitor and hUMSC-EVs at half doses outperformed full-dose monotherapies, accelerating wound healing through synergistic effects on collagen synthesis, cell proliferation, migration, and angiogenesis.Mon Aug 18 00:00:00 GMT+01:00 2025PXD0674449606