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May 18, 2026Open Access

Injectable polysaccharide-based hydrogel delivering Poria cocos extracellular vesicles promotes hair regeneration in androgenetic alopecia via Wnt/β-catenin signaling

HLHuiting LuoChongqing Medical University SWShang WangHuazhong Agricultural University HWHantao WangChongqing Medical University

Key Points

The aim is to assess the efficacy of a polysaccharide-based hydrogel delivering Poria cocos extracellular vesicles in promoting hair regeneration during androgenetic alopecia.
Developed a biomacromolecular hydrogel comprising sodium carboxymethylcellulose, sodium alginate, and hyaluronic acid for Poria cocos EV delivery.
Administered the hydrogel in a dihydrotestosterone-induced AGA mouse model.
Performed transcriptomic profiling to assess signaling pathway activation.
Topical application of PCEV@CMC/SA hydrogel significantly accelerated hair regrowth and enhanced follicle density.
Activated Wnt/beta-catenin signaling correlated with increased expression of hair differentiation markers and decreased stem-cell quiescence markers.
Demonstrated that the delivery platform effectively stabilizes and retains PCEVs in the follicular niche.

Abstract

Androgenetic alopecia (AGA) is characterized by progressive hair follicle miniaturization driven by premature follicle regression. While extracellular vesicles (EVs) are potent bioactive therapeutics, their clinical translation is hindered by the low yields and poor stability of mammalian-derived sources. Herein, we developed an injectable biomacromolecular hydrogel composed of sodium carboxymethylcellulose (CMC Na), sodium alginate (SA), and hyaluronic acid (HA) to deliver plant-derived Poria cocos extracellular vesicles (PCEVs) for the topical treatment of AGA. This polysaccharide matrix was engineered to localize vesicular cargo within the follicular niche, preserve vesicle integrity, and facilitate the sustained release of PCEVs. The hydrogel exhibited favorable rheological properties, injectability, and cytocompatibility for topical application. In a dihydrotestosterone (DHT)-induced AGA mouse model, topical administration of the PCEV-loaded hydrogel significantly accelerated hair regrowth, enhanced follicle density, and restored hair bulb volume and dermal thickness. Transcriptomic profiling revealed that the therapeutic effect was driven by Wnt/β-catenin signaling activation. Specifically, PCEVs treatment led to the upregulation of differentiation markers homeobox C13 ( Hoxc13 ) and forkhead box N1 ( Foxn1 ), hair-shaft keratin Krt31 , and desmoglein 4 ( Dsg4 ), along with the downregulation of stem-cell quiescence markers nuclear factor of activated T cells 1 ( Nfatc1 ) and Cd34 . Collectively, this delivery platform effectively leverages plant-derived EV cargo to reverse stem-cell quiescence and promote follicular regeneration, offering a scalable and stable translational strategy for hair loss disorders. • PCEV@CMC/SA hydrogel accelerates hair regeneration via activating Wnt/β-catenin signaling. • Tangential flow filtration enables high-yield isolation of plant-derived PCEVs. • PCEV@CMC/SA enhances PCEV stability, retention, and delivery to hair follicles. • Poria cocos -based platform provides scalable strategy for AGA therapy.

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