研究背景和目的：冻伤是常见的冷损伤，是组织器官暴露于寒冷环境中所致的组织缺血、细胞坏死以及局部炎症而引起的损伤。全层皮肤冻伤所导致的皮肤溃疡常发展为慢性难愈性皮肤溃疡。这种皮肤溃疡往往会导致瘢痕的形成，影响外观和功能，给患者造成生理和心理双重负担，而且这种溃疡容易继发皮肤癌变。因此，亟需一种快速治愈冻伤所致溃疡的方法。

研究方法：我们使用裸鼠全层皮肤冻伤模型来评估冻伤后的皮肤溃疡的恢复过程。此外，我们还揭示了冻伤期间皮肤中表皮细胞、成纤维细胞以及炎症细胞的变化模式。最重要的是，我们首次使用明胶水凝胶包被人诱导多能干细胞来源的皮肤类器官治疗冻伤所致皮肤溃疡。

研究结果：通过皮肤类器官治疗可以减少冻伤后的早期炎症水平，增加表皮干细胞的比例，显著加速了冻伤所致溃疡的愈合。此外，在伤口愈合的后期，皮肤类器官降低了冻伤所致溃疡皮损中成纤维细胞的整体比例，显著减少皮肤中的成纤维细胞向着肌成纤维细胞的转变，并通过细胞外基质（Extracellular Matrix, ECM）降解和重塑机制重塑细胞微环境，促进生理性ECM的恢复，减少异常ECM的聚积，从而减少皮肤瘢痕的形成。

结论：皮肤类器官可促进冻伤所致皮肤溃疡快速愈合和促进皮肤功能恢复。本研究为冻伤及其他原因所引起的慢性皮肤溃疡和皮肤功能障碍患者提供了一种全新的治疗方法。

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.