Tβ4-Engineered ADSC Extracellular Vesicles Rescue Cell Senescence Through Separable Microneedle Patches for Diabetic Wound Healing.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Microneedles loaded with bioactive substances have demonstrated efficacy in wound healing, while their application in the elderly chronic wounds, aggravated by cellular senescence, is still a significant challenge. Here, a novel therapeutic strategy is presented utilizing Thymosin β4 (Tβ4)-modified adipose-derived stem cell extracellular vesicles (ADSC-EVs) delivered via separable microneedle patches (MN@EVs Tβ4 ). The therapeutic EVs Tβ4 are derived from ADSCs that overexpress Tβ4, a factor that reverses cellular senescence. Leveraging the drug-loading and release properties of gelatin methacryloyl and poly(ethylene glycol) diacrylate, EVs Tβ4 are encapsulated within the tips of the microneedles. Notably, the soluble hyaluronic acid base layer dissolves rapidly and separates from the tips upon exudate absorption, enabling a sustained release of EVs Tβ4 . Subsequently, it is demonstrated its ability to mitigate senescence and improve function via the PTEN/PI3K/AKT pathway. Furthermore, MN@EVs Tβ4 patches showed significant efficacy in reversing senescence and promoting wound healing in diabetic wound models. Thus, the engineered ADSC-EVs, combined with separable microneedle patches, represent a promising bioengineering strategy for clinical wound management.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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