@article{Liu2026, 
author = {Enze Liu and Ying Li and Pei Wang and Zhen Gao and Jiayingzi Wu and Xiansong Wang},
title = {Lymphatic remodeling and metabolic rescue by VEGFR-3/DHA-coordinated microneedles for hair regeneration},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {5},
pages = {94908541},
keywords = {androgenetic alopecia, hair follicle stem cells, lymphatic remodeling, lipid metabolism, microneedle delivery},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908541},
doi = {10.26599/NR.2026.94908541},
abstract = {Androgenetic alopecia (AGA) is characterized by progressive follicle miniaturization, excessive inflammation and hair follicle stem cell (HFSC) quiescence. To address these multifactorial challenges, we developed a dissolvable γ-polyglutamic acid (γ-PGA) hydrogel microneedle system (VI@MSN/MNs-DHA) delivering: (1) Vascular endothelial growth factor receptor 3 (VEGFR-3) inhibitor (VI) encapsulated in mesoporous silica nanoparticles (MSNs) to remodel lymphatic vessel endothelial hyaluronan receptor 1-positive (LYVE1+) lymphatic networks and thereby reduce anatomical constraints on anagen entry, and (2) docosahexaenoic acid (DHA) to normalize lipid metabolism and oxidative stress. In vitro, VI@MSN/MN-DHA extracts demonstrated multiple bioactivities, including the suppression of lymphatic endothelial tube formation, scavenging of reactive oxygen species, and protection of HFSCs from testosterone-induced injury. In vivo, topical application of VI@MSN/MN-DHA in an AGA mouse model accelerated anagen onset and increased hair regrowth density by 1.37-fold compared to the untreated group. Mechanistically, it is identified that the treatment of VI@MSN/MN-DHA led to the coordinated upregulation of SRY-box transcription factor 9 (SOX9) and Ki67 in HFSCs, along with restoration of peroxisome proliferator-activated receptor-γ signaling. This study presents a novel strategy that combines lymphatic remodeling and metabolic reprogramming to effectively reactivate HFSCs and promote hair regeneration. The minimally invasive microneedle platform offers a novel microenvironment-engineering paradigm for safe and effective AGA therapy.}
}