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The dermal papilla dilemma and potential breakthroughs in bioengineering hair follicles

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Abstract

The generation and growing of de novo hair follicles is the most daring hair replacement approach to treat alopecia. This approach has been explored at least since the 1960s without major success. Latest in the 1980s, the realization that the mesenchymal compartment of hair follicles, the dermal papilla (DP), is the crucial signaling center and element required for fulfilling this vision of hair follicle engineering, propelled research into the fibroblasts that occupy the DP. However, working with DP fibroblasts has been stubbornly frustrating. Decades of work in understanding the nature of DP fibroblasts in vitro and in vivo have led to the appreciation that hair follicle biology is complex, and the dermal papilla is an enigma. Functional DP fibroblasts tend to aggregate in 2D culture, while impaired DP cells do not. This fact has stimulated recent approaches to overcome the hurdles to DP cell culture by mimicking their natural habitat, such as growing DP fibroblasts in three dimensions (3D) by their self-aggregation, adopting 3D matrix scaffold, or bioprinting 3D microstructures. Furthermore, including keratinocytes in the mix to form hair follicle-like composite structures has been explored but remains a far cry from a useful and affordable method to generate human hair follicles in sufficient quantity and quality in a practical time frame for patients. This suggests that the current strategies may have reached their limitations in achieving successful hair follicle bioengineering for clinical applications. Novel approaches are required to overcome these barriers, such as focusing on embryonic cell types and processes in combination with emerging techniques.

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Funding

This work was supported by NIH 1R21AR073380-01 (YZ), 1R21AR078976-01 (YZ), and 1R01AR077238-01A1 (YZ).

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Authors and Affiliations

  1. Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA

    Thomas Andl

  2. Division of Pharmaceutical Science, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA

    Linli Zhou & Yuhang Zhang

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  1. Thomas Andl
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  2. Linli Zhou
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  3. Yuhang Zhang
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All authors wrote the main manuscript text, and L. Z and Y.Z. prepared the figures. All authors reviewed and approved the final version to be published. All authors agree to be accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; furthermore, the authors have confidence in the integrity of the contributions of their coauthors.

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Correspondence to Yuhang Zhang.

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TA is a consultant for Stemson Therapeutics, LLC. All other authors declare no competing interests.

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Andl, T., Zhou, L. & Zhang, Y. The dermal papilla dilemma and potential breakthroughs in bioengineering hair follicles. Cell Tissue Res 391, 221–233 (2023). https://doi.org/10.1007/s00441-022-03730-w

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