Senolytic-loaded asymmetric wound dressing for targeted senescent cell clearance in diabetic wound healing.

Abstract

Chronic wounds, especially diabetic foot ulcers, pose a major clinical challenge due to persistent inflammation, impaired angiogenesis, and cellular senescence. Senolytic therapies, which selectively eliminate senescent cells, have shown promise in promoting healing, but systemic toxicity limits their application. To address this, we developed an asymmetric fabric-based composite platform for localized senolytic delivery. Using single-cell RNA sequencing, we characterized senescence-associated alterations in human diabetic foot ulcer tissues and screened several senolytic candidates in skin fibroblasts and endothelial cells. Among these, navitoclax (ABT-263) emerged as the most effective senolytic. Incorporating ABT-263 into the fabric-based platform to prepare ABT-263-CGH, we confirmed its ability to reduce senescent cell burden while maintaining biocompatibility. In a diabetic mouse model, the ABT-263-CGH significantly enhanced wound healing, reduced senescence markers, and exhibited no detectable systemic toxicity. These findings highlight the potential of localized senolytic therapy using an asymmetric fabric-based wound dressing as a novel strategy for enhancing chronic wound healing, offering a promising therapeutic avenue for diabetic wound management, and paving the way for future clinical applications.