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Dual-Barb Microneedle with JAK/STAT Inhibitor-Loaded Nanovesicles Encapsulation for Tendinopathy
Minhao Chen1, Fengkai Zou1,2, Pei Wang3
1Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China.
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.
Insights
A new microneedle patch delivers JAK/STAT inhibitor-loaded nanovesicles to tendon stem cells, promoting repair. This approach enhances tendon healing and offers a promising treatment for tendinopathy.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Cell Biology
Background:
- Tendon stem/progenitor cells (TSPCs) are vital for tendon repair and homeostasis.
- Aberrant Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation impairs TSPCs, leading to tendinopathy.
- Conventional drug delivery methods have limited efficacy due to poor drug retention at the injury site.
Purpose of the Study:
- To develop a novel poly-gamma-glutamic acid (γ-PGA) dual-barb microneedle (MN) patch for targeted delivery of nanovesicles (NVs) containing a JAK/STAT inhibitor (WP1066).
- To evaluate the efficacy of the MN-WP1066-NVs system in treating tendinopathy by enhancing TSPCs function and restoring tendon structure.
Main Methods:
- Fabrication of a dual-barb γ-PGA microneedle patch loaded with WP1066-encapsulated NVs derived from TSPCs.
- In vitro and in vivo assessments of microneedle degradation, drug release kinetics, and therapeutic effects on TSPCs and tendon tissue.
- Evaluation of JAK/STAT pathway inhibition, inflammation reduction, extracellular matrix preservation, and histological repair.
Main Results:
- The dual-barb MN patch demonstrated firm skin adhesion and sustained release of WP1066-NVs.
- WP1066-NVs effectively promoted TSPCs self-renewal, migration, and stemness.
- Treatment significantly alleviated inflammation, reduced extracellular matrix degradation, and restored tendon histological integrity by inhibiting the JAK/STAT pathway.
Conclusions:
- The γ-PGA dual-barb microneedle patch provides a sustained and localized delivery of WP1066-NVs for tendinopathy treatment.
- This innovative therapeutic strategy effectively targets the JAK/STAT pathway, enhances TSPCs function, and promotes tendon regeneration.
- The multifunctional microneedle patch represents a promising advancement in managing tendinopathy.
