Theranostics 2020; 10(3):1454-1478. doi:10.7150/thno.39566

Research Paper

Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth

Yuxin Chen1*, Junfei Huang1*, Ruosi Chen1, Lunan Yang1, Jin Wang1, Bingcheng Liu1, Lijuan Du1, Yanhua Yi1, James Jia1, Yanwei Xu2, Qian Chen1, Djakaya Guydidier Ngondi1, Yong Miao1✉, Zhiqi Hu1✉

1. Department of Plastic and Aesthetic Surgery Nanfang Hospital of Southern Medical University Guangzhou, Guangdong Province, 510515, China.
2. Central laboratory of the Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
*These authors contributed equally to this work.

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Citation:
Chen Y, Huang J, Chen R, Yang L, Wang J, Liu B, Du L, Yi Y, Jia J, Xu Y, Chen Q, Ngondi DG, Miao Y, Hu Z. Sustained release of dermal papilla-derived extracellular vesicles from injectable microgel promotes hair growth. Theranostics 2020; 10(3):1454-1478. doi:10.7150/thno.39566. Available from http://www.thno.org/v10p1454.htm

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Abstract

Hair regeneration has long captured researchers' attention because alopecia is a common condition and current therapeutic approaches have significant limitations. Dermal papilla (DP) cells serve as a signaling center in hair follicles and regulate hair formation and cycling by paracrine secretion. Secreted EVs are important signaling mediators for intercellular communication, and DP-derived extracellular vesicles (DP-EVs) may play an important role in hair regeneration. However, the instability of EVs in vivo and their low long-term retention after transplantation hinder their use in clinical applications.

Methods: Human DP-EVs were encapsulated in partially oxidized sodium alginate (OSA) hydrogels, yielding OSA-encapsulated EVs (OSA-EVs), which act as a sustained-release system to increase the potential therapeutic effect of DP-EVs. The ability of the OSA-EVs to protect protein was assessed. The hair regeneration capacity of OSA-EVs, as well as the underlying mechanism, was explored in hair organ culture and a mouse model of depilation.

Results: The OSA-EVs were approximately 100 μm in diameter, and as the hydrogel degraded, DP-EVs were gradually released. In addition, the hydrogel markedly increased the stability of vesicular proteins and increased the retention of EVs in vitro and in vivo. The OSA-EVs significantly facilitated proliferation of hair matrix cells, prolonged anagen phase in cultured human hairs, and accelerated the regrowth of back hair in mice after depilation. These effects may be due to upregulation of hair growth-promoting signaling molecules such as Wnt3a and β-catenin, and downregulation of inhibitory molecule BMP2.

Conclusion: This study demonstrated that OSA hydrogels promote the therapeutic effects of DP-EVs, and indicate that our novel OSA-EVs could be used to treat alopecia.

Keywords: extracellular vesicles, oxidized sodium alginates, dermal papilla, hair regrowth, sustained release.