Tissue engineering strategies for human hair follicle regeneration: How far from a hairy goal?

The demand for an efficient therapy for alopecia disease has fueled the hair research field in recent decades. However, despite significant improvements in the knowledge of key processes of hair follicle biology such as genesis and cycling, translation into hair follicle replacement therapies has not occurred. Great expectation has been recently put on hair follicle bioengineering, which is based on the development of fully functional hair follicles with cycling activity from an expanded population of hair-inductive (trichogenic) cells. Most bioengineering approaches focus on in vitro reconstruction of folliculogenesis by manipulating key regulatory molecular/physical features of hair follicle growth/cycling in vivo. Despite their great potential, no cell-based product is clinically available for hair regeneration therapy to date. This is mainly due to demanding issues that still hinder the functionality of cultured human hair cells. The present review comprehensively compares emergent strategies using different cell sources and tissue engineering approaches, aiming to successfully achieve a clinical cure for hair loss. The hurdles of these strategies are discussed, as well as the future directions to overcome the obstacles and fulfill the promise of a "hairy" feat.