Research into the application of regenerative medicine techniques to regrowth of hair has been ongoing for some time. In principle, the hair follicle is a structure that could be engineered and implanted, or existing follicles induced to restored activity in some way. In practice this is challenging, and most forms of progressive hair loss are far from fully understood at the level of cellular biochemistry in the hair follicle: there is no great guarantee that generating or providing new follicles would have the desired effect, given the surrounding environment and its signaling.

Up to date, treatments for hair loss (alopecia) include pharmacological and surgical (autologous hair transplant) interventions. Although hair restoration surgery is nowadays the most effective method, donor hair follicles (HFs) scarcity is often its major limitation. Besides, pharmacological treatments still not fully satisfy the patient's needs and entail drastic side effects. Thus, the limited efficacy and possible side effects of the current treatments have fostered the search for alternative therapeutic solutions, capable of generating unlimited number of HFs de novo.

Of note, stem cell-based tissue engineering is emerging as the most thriving approach, aiming to reconstruct HFs in vitro to replace lost or damaged HFs as a consequence of disease, injury, or aging. HF bioengineering approaches are based on the accumulated knowledge on reciprocal epithelial-mesenchymal (EM) interactions controlling embryonic organogenesis and postnatal HF cyclic growth. However, despite recent progress in the field, clinical applications of tissue engineering strategies for hair loss are still missing. Neogenesis of human follicles derived from cultured HF dermal cells has not been successfully achieved yet.

A regenerative medicine therapy for human hair loss will only be successfully achieved when HF are formed de novo following implementation of in vitro bioengineered structures into the patient's bald scalp. Importantly, although from a scientific perspective studies have achieved and reported HF regeneration from human cells, the caveats are whether (a) there is any mouse contribution in HF neogenesis from human bioengineered structures transplanted into mouse skin, and (b) human bioengineered structures will generate HF that besides growing/cycling also mimetic natural hair type and are responsive to physiological stimuli.

Moreover, significant limitations may further hamper an operational clinical solution for hair loss. First, bioengineered hair reconstruction will imply large-scale production of cell-based structures and the development of well-defined culture expansion media for clinical usage. Robust culture systems that allow stem cell expansion while maintaining their intrinsic properties are still missing. Second, even if generation of functional and cycling HF units is achieved, a huge gap still exists until the conception of a clinically relevant bioengineered product that responds to physiological stimuli (eg, neuronal stimuli) and aesthetic context (hair type, density, pigmentation, and orientation).