Dual‐Barb Microneedle with JAK/STAT Inhibitor‐Loaded Nanovesicles Encapsulation for Tendinopathy

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.