Single-cell analysis reveals Cxcl14+ progenitor fibroblast accumulation in regenerating diabetic wound after carbon monoxide-releasing hydrogel therapy

Chronic and non-healing skin wound is one of grievous complications of diabetes. In this study, we demonstrated a gas (carbon monoxide)-releasing hyaluronic acid hydrogel (i.e. COHAG) in promoting diabetic wound healing. Our results show that the COHAG significantly accelerated the healing process in diabtic rat full-thickness skin defect model, as compared with hydrogel without gas-releasing molecule and untreated group. Single-cell analysis of regenerating skin samples revealed that Cxcl14-overexpressing (Cxcl14+) fibroblast with progenitor properties are abundantly accumulated at the wound site after COHAG therapy.慢性难愈性皮肤创面是糖尿病的严重并发症之一。本研究中，我们证实了一种可释放一氧化碳（carbon monoxide）的透明质酸（hyaluronic acid）水凝胶（即COHAG）可促进糖尿病创面愈合。我们的研究结果显示，与未负载释气分子的水凝胶组及未处理组相比，COHAG可显著加速糖尿病大鼠全层皮肤缺损模型的创面愈合进程。对再生皮肤样本进行的单细胞分析（single-cell analysis）显示，经COHAG治疗后，具备祖细胞特性的Cxcl14过表达（Cxcl14+）成纤维细胞（fibroblast）在创面部位大量富集。