Abstract

The hair follicle (HF) is an exquisite skin appendage endowed with cyclical regenerative capacity; however, de novo follicle formation does not naturally occur. Consequently, patients suffering from extensive skin damage or hair loss are deprived of the HF critical physiological and/or aesthetic functions, severally compromising skin function and the individual's psychosocial well‐being. Translation of regenerative strategies has been prevented by the loss of trichogenic capacity that relevant cell populations undergo in culture and by the lack of suitable human‐based in vitro testing platforms. Here, we provide a comprehensive overview of the major difficulties associated with HF regeneration and the approaches used to overcome these drawbacks. We describe key cellular requirements and discuss the importance of the HF extracellular matrix and associated signaling for HF regeneration. Finally, we summarize the strategies proposed so far to bioengineer human HF or hair‐bearing skin models and disclose future trends for the field.

Highlights

  • The hair follicle (HF) is an exquisite skin appendage endowed with cyclical regenerative capacity; de novo follicle formation does not naturally occur

  • Cell culture is typically performed under atmospheric O2 levels (21% O2, normoxia) but in vivo physiological levels usually range between 1 and 11% O2.57 Comparably to cells cultured under normoxia, human DP (hDP) cells cultured in 2% O2 showed a significant increase in alkaline phosphatase (ALP) activity, a recognized dermal papilla (DP) cell inductive marker,[50,58] suggesting improved hair inductive capacity

  • We have recently demonstrated that human interfollicular epidermis (IFE) epithelial cells with stem-like features, isolated by fluorescenceactivated cell sorting based on their α6-integrinbri/CD71dim expression, were capable of supporting the formation of immature HFs and sebaceous gland (SG) when co-transplanted with hDP cells in mice,[84] representing a promising epithelial cell source for HF regeneration

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Summary

REVIEW ARTICLE

Recreation of a hair follicle regenerative microenvironment: Successes and pitfalls. 13B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark–Parque de Ciência e Tecnologia, University of Minho, Guimar~aes, Portugal 2ICVS/3B's–PT Government Associate Laboratory, Guimar~aes, Portugal. Recreation of a hair follicle regenerative microenvironment: Successes and pitfalls. 13B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark–Parque de Ciência e Tecnologia, University of Minho, Guimar~aes, Portugal 2ICVS/3B's–PT Government Associate Laboratory, Guimar~aes, Portugal. Funding information Consolidator grant “ECM_INK”, Grant/Award Number: ERC-2016-COG-726061; Fundaç~ao para a Ciência e a Tecnologia, Grant/Award Numbers: PD/59/2013, PD/ BD/113800/2015, IF/00945/2014

In vivo outcomes
Dermal fibroblasts were mixed with collagen I and
DP or DS cells were encapsulated in a collagen I gel
Folliculoid microsphere
Follicular DP structures
In vitro structures HF organoid model
Epidermal invaginations or folliculoid structures
HF generation within reconstructed skin
Findings
| CONCLUSION AND FUTURE TRENDS
Full Text
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