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

Abstract

Abstract 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. Significance statement Hair loss (alopecia) affects a growing number of people worldwide. Limited efficacy and side effects of current pharmacological and surgical treatments have fostered the search for alternative therapeutic solutions. Great expectation has been recently put on hair follicle bioengineering, which is based on the development of functional hair follicles from an expanded population of hair-inductive cells. However, human follicle neogenesis resorting to patient's cells was not successfully achieved yet. Based on recent advances in the field, this review on cell-based hair follicle tissue engineering systematically compiles the emerging strategies while disclosing the hurdles that still limit translation into the clinics.