Lymphatic remodeling and metabolic rescue by VEGFR-3/DHAcoordinated microneedles for hair regenerationOA
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 dissolvableγ-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-γsignaling.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.
Enze Liu;Ying Li;Pei Wang;Zhen Gao;Jiayingzi Wu;Xiansong Wang
Department of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People''s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,ChinaDepartment of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People''s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,ChinaDepartment of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People''s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,ChinaDepartment of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People''s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,ChinaGuangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging,School of Biomedical Engineering,Medical School Shenzhen University,Shenzhen University,Shenzhen 518055,ChinaDepartment of Plastic and Reconstructive Surgery,Shanghai Key Laboratory of Tissue Engineering,Shanghai Ninth People''s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China
医药卫生
androgenetic alopeciahair follicle stem cellslymphatic remodelinglipid metabolismmicroneedle delivery
《Nano Research》 2026 (5)
P.914-929,16
supported by the National Natural Science Foundation of China(Nos.31971271 and 22474079)Natural Science Foundation of Guangdong Province(No.2024A1515012677)Basic Research Program of Shenzhen(No.JCYJ20240813142810014)Shenzhen University 2035 Program for Excellent Research(No.2024C004)。
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