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Updated: Jun 28, 2025
Optimizing Extracellular Vesicle Delivery Using a Core-Sheath 3D-Bioprinted Scaffold for Chronic Wound Management
Published on: February 28, 2025
Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle
Yu Zhuang1, Shengjie Jiang1, Xiaoling Deng1
1Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology; Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China.
Abstract:
Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.
Insights
Metformin engineered extracellular vesicles (Met-EVs) rejuvenate aging skin by restoring cellular energy metabolism. This enhances wound repair in aged skin by improving mitochondrial function and mitophagy.
Area of Science:
- Gerontology and Regenerative Medicine
- Cellular Metabolism and Aging
- Biotechnology and Nanomedicine
Background:
- Aging skin exhibits impaired wound repair due to accumulated senescent cells (SnCs) and altered metabolic regulation.
- Adequate adenosine triphosphate (ATP) production is crucial for cell activation and tissue repair in aged individuals.
- Interventions targeting cellular ATP metabolism present a promising therapeutic avenue for age-related skin defects.
Purpose of the Study:
- To investigate energy metabolic changes in aging skin.
- To evaluate the efficacy of metformin engineered extracellular vesicles (Met-EVs) in ameliorating skin aging and enhancing repair.
- To elucidate the underlying mechanisms of Met-EVs in restoring cellular function and ATP metabolism in aged skin.
Main Methods:
- Analysis of energy metabolism in aging skin from human patients and mice.
- Administration of Met-EVs to aged mice to assess skin repair efficacy.
- Evaluation of cellular senescence, mitochondrial function, glycolysis, oxidative phosphorylation (OXPHOS), and mitophagy following Met-EV treatment.
Main Results:
- Met-EV treatment significantly enhanced aged mouse skin repair and ameliorated cellular senescence.
- Met-EVs restored cellular dysfunctions by remodeling ATP metabolism, characterized by reduced glycolysis and enhanced OXPHOS.
- Met-EVs rescued senescence-induced mitochondrial dysfunctions and mitophagy suppressions, promoting adequate ATP production.
Conclusions:
- Extracellular vesicles engineered with metformin (Met-EVs) can rejuvenate senescent cells and facilitate aged tissue repair.
- The therapeutic effect of Met-EVs involves the remodeling of mitochondrial function via mitophagy for enhanced ATP production.
- Disturbed energy metabolism in aging is a viable therapeutic target for improving age-related skin defects and promoting repair.
