Sweat gland regeneration: Current strategies and future opportunities

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.