Functional regeneration strategies of hair follicles: advances and challenges

Hair follicles are essential appendages of human skin that function in protection, sensation, thermoregulation and social interactions. The multicellular components, particularly the dermal papilla, matrix and bulge housing stem cells, enable cyclic hair growth postnatally. However, miniaturization and loss of hair follicles can occur in the context of ageing, trauma and various alopecia-related diseases. Conventional treatments involve the redistribution of existing follicles, which may not be viable in patients lacking follicular resources. Recent progress in the comprehension of morphogenesis and the development of biomaterials has significantly advanced follicle reconstruction, incorporating organ germ assembling, stem cell induction and bioprinting techniques. Despite these advancements, fully restoring hair follicles remains challenging due to the complexities of replicating embryonic signals and sustaining growth cycles. Identifying suitable cell sources for clinical applications also presents a hurdle. Here, we retrospect the progress made in the field of hair follicle regeneration, aiming to offer an exhaustive analysis on the benefits and limitations of these methods, and to foster the development of innovative solutions.