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Published on: August 21, 2021
Senolytic-loaded asymmetric wound dressing for targeted senescent cell clearance in diabetic wound healing
Ming Zhang1, Yamei Wang2, Yao Dai1
1Department of Geriatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Insights
This study developed a novel fabric-based wound dressing for localized senolytic therapy. The dressing effectively enhanced diabetic wound healing in mice by reducing senescent cells without systemic toxicity.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Wound Healing Research
Background:
- Chronic wounds, particularly diabetic foot ulcers, present significant clinical challenges due to inflammation, poor blood vessel formation, and cellular aging (senescence).
- Current senolytic therapies, which target senescent cells, show potential for healing but can cause systemic toxicity.
- Localized delivery systems are needed to overcome the limitations of systemic senolytic administration.
Purpose of the Study:
- To develop and evaluate an asymmetric fabric-based composite platform for localized delivery of senolytic agents.
- To investigate the efficacy of navitoclax (ABT-263) incorporated into this platform for treating diabetic wounds.
- To assess the safety and therapeutic potential of localized senolytic therapy in a preclinical model.
Main Methods:
- Single-cell RNA sequencing was used to analyze senescence in diabetic foot ulcer tissues.
- Navitoclax (ABT-263) was identified as an effective senolytic agent and incorporated into a fabric platform (ABT-263-CGH).
- The efficacy and biocompatibility of ABT-263-CGH were evaluated in a diabetic mouse wound healing model.
Main Results:
- The developed ABT-263-CGH platform successfully reduced senescent cell burden and demonstrated biocompatibility.
- In diabetic mice, ABT-263-CGH significantly accelerated wound healing compared to controls.
- Treatment with ABT-263-CGH showed reduced senescence markers and no detectable systemic toxicity.
Conclusions:
- Localized senolytic therapy using an asymmetric fabric-based wound dressing is a promising strategy for chronic wound healing.
- This approach offers a novel therapeutic avenue for managing diabetic wounds with improved safety and efficacy.
- The findings support the potential clinical application of this localized senolytic delivery system for wound management.
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