For patients with extensive skin defects, loss of sweat glands (SwGs) greatly decreases their quality of life. Indeed, difficulties in thermoregulation, ion reabsorption, and maintaining fluid balance might render them susceptible to hyperthermia, heatstroke, or even death. Despite extensive studies on the stem cell biology of the skin in recent years, in-situ regeneration of SwGs with both structural and functional fidelity is still challenging because of the limited regenerative capacity and cell fate control of resident progenitors. To overcome these challenges, one must consider both the intrinsic factors relevant to genetic and epigenetic regulation and cues from the cellular microenvironment. Here, we describe recent progress in molecular biology, developmental pathways, and cellular evolution associated with SwGdevelopment and maturation. This is followed by a summary of the current strategies used for cell-fate modulation, transmembrane drug delivery, and scaffold design associated with SwGregeneration. Finally, we offer perspectives for creating more sophisticated systems to accelerate patients’ innate healing capacity and developing engineered skin constructs to treat or replace damaged tissues structurally and functionally.

对于皮肤严重缺损的患者，汗腺（SwGs）的丢失会大大降低其生活质量。确实，温度调节，离子重吸收和维持体液平衡方面的困难可能使它们容易遭受体温过高，中暑甚至死亡。尽管近年来对皮肤的干细胞生物学进行了广泛的研究，但是具有结构和功能保真性的SwGs的原位再生仍然具有挑战性，因为其再生能力和驻体祖细胞的细胞控制能力有限。为了克服这些挑战，必须同时考虑与遗传和表观遗传调控有关的内在因素以及来自细胞微环境的线索。在这里，我们描述了与SwG发育和成熟相关的分子生物学，发育途径和细胞进化的最新进展。接下来是对目前用于细胞命运调节，跨膜药物递送以及与SwGregeneration相关的支架设计的策略的概述。最后，我们提供了创建更复杂的系统以加速患者的先天治愈能力以及开发工程皮肤构造以治疗或替换受损组织的结构和功能的观点。