斯达
贾纳斯激酶
肌腱
肌腱病
细胞生物学
祖细胞
JAK-STAT信号通路
STAT蛋白
细胞外基质
癌症研究
医学
信号转导
化学
车站3
药理学
干细胞
生物
解剖
酪氨酸激酶
作者
Minhao Chen,Fengkai Zou,Pei Wang,Wenbo Hu,Peng Shen,X. D. Wu,Hua Xu,Yunfeng Rui,Xiansong Wang,Youhua Wang
标识
DOI:10.1002/adhm.202401512
摘要
Abstract Tendon stem/progenitor cells (TSPCs) are crucial for tendon repair, regeneration, and homeostasis. Dysfunction of TSPCs, due to aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, contributes to tendinopathy. Unfortunately, the effectiveness of conventional subcutaneous injection targeting at suppressing JAK/STAT signaling pathway is limited due to the passive diffusion of drugs away from the injury site. Herein, a novel poly‐gamma‐glutamic acid (γ‐PGA) dual‐barb microneedle (MN) path loaded with TSPCs‐derived nanovesicles (NVs) containing JAK/STAT inhibitor WP1066 (MN‐WP1066‐NVs) for tendinopathy treatment is designed. The dual‐barb design of the MN ensures firm adhesion to the skin, allowing for sustained and prolonged release of WP1066‐NVs, facilitating enhanced TSPCs self‐renewal, migration, and stemness in tendinopathy. In vitro and in vivo experiments demonstrate that the degradation of γ‐PGA patch tips facilitates the gradual release of WP1066‐NVs at the lesion site. This release alleviates inflammation, suppresses extracellular matrix degradation, and restores normal tendon histological structure by inhibiting the JAK/STAT pathway. These findings suggest that the multifunctional dual‐barb MN patch offers a novel and effective therapeutic strategy for tendinopathy treatment.
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