Tissue engineering of human hair follicles using a biomimetic developmental approach

Nat Commun. 2018 Dec 13;9(1):5301. doi: 10.1038/s41467-018-07579-y.


Human 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / pathology
  • Alopecia / therapy*
  • Animals
  • Biomimetics
  • Cell Differentiation
  • Cells, Cultured
  • Dermis / cytology*
  • Hair Follicle / cytology
  • Hair Follicle / growth & development*
  • Hair Follicle / transplantation*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / biosynthesis
  • Male
  • Mice
  • Mice, Nude
  • Tissue Engineering / methods*
  • Transplantation, Heterologous


  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1