Bioinspired engineering ADSC nanovesicles thermosensitive hydrogel enhance autophagy of dermal papilla cells for androgenetic alopecia treatment

Jiachao Xiong; Zhixiao Liu; Lingling Jia; Yulin Sun; Rong Guo; Tingting Xi; Zihan Li; Minjuan Wu; Hua Jiang; Yufei Li

doi:10.1016/j.bioactmat.2024.02.023

Bioinspired engineering ADSC nanovesicles thermosensitive hydrogel enhance autophagy of dermal papilla cells for androgenetic alopecia treatment

Bioact Mater. 2024 Mar 1:36:112-125. doi: 10.1016/j.bioactmat.2024.02.023. eCollection 2024 Jun.

Authors

Jiachao Xiong^{1

2}, Zhixiao Liu³, Lingling Jia¹, Yulin Sun^{1

2}, Rong Guo¹, Tingting Xi¹, Zihan Li⁴, Minjuan Wu³, Hua Jiang¹, Yufei Li¹

Affiliations

¹ Department of Plastic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
² Medical College, Tongji University, Shanghai, 200331, China.
³ Department of Histology and Embryology, Naval Medical University, Shanghai, 200433, China.
⁴ St Hugh's College, University of Oxford, OX2 6LE, United Kingdom.

Abstract

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-A^OE@NV). The incorporation of JAM-A^OE@NV into a thermosensitive hydrogel matrix (JAM-A^OE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-A^OE@NV, and resulted in the achievement of a sustained-release profile for JAM-A^OE@NV. The physicochemical characteristics of the JAM-A^OE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-A^OE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.

Keywords: Androgenic alopecia; Autophagy; Hydrogel; JAM-A; Nanovesicles.