01832nas a2200301   4500000000100000000000100001008004100002260001500043653002700058653001800085653001600103100002200119700002000141700001700161700001500178700001900193700001700212700001600229700001700245700002000262700002500282245008900307856005500396300000900451490000600460520105000466022001401516       2018                            d  c2018-12-1310aBiomedical Engineering10aOrganogenesis10aSkin models1 aHasan Erbil Abaci1 aAbigail Coffman1 aYanne Doucet1 aJames Chen1 aJoanna Jacków1 aEtienne Wang1 aZongyou Guo1 aJung U. Shin1 aColin A. Jahoda1 aAngela M. Christiano00aTissue engineering of human hair follicles using a biomimetic developmental approach  uhttps://www.nature.com/articles/s41467-018-07579-y  a53010 v93 aHuman skin constructs (HSCs) have the potential to provide an effective therapy for patients with significant skin injuries and to enable human-relevant drug screening for skin diseases; however, the incorporation of engineered skin appendages, such as hair follicles (HFs), into HSCs remains a major challenge. Here, we demonstrate a biomimetic approach for generation of human HFs within HSCs by recapitulating the physiological 3D organization of cells in the HF microenvironment using 3D-printed molds. Overexpression of Lef-1 in dermal papilla cells (DPC) restores the intact DPC transcriptional signature and significantly enhances the efficiency of HF differentiation in HSCs. Furthermore, vascularization of hair-bearing HSCs prior to engraftment allows for efficient human hair growth in immunodeficient mice. The ability to regenerate an entire HF from cultured human cells will have a transformative impact on the medical management of different types of alopecia, as well as chronic wounds, which represent major unmet medical needs.  a2041-1723