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      Engineered Extracellular Vesicles in Wound Healing: Design, Paradigms, and Clinical Application

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      Wiley

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          Abstract

          The severe quality of life and economic burden imposed by non‐healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell‐free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.

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          Most cited references225

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          Biological properties of extracellular vesicles and their physiological functions

          In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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            Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication

            The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ill-defined. Here, we discuss the current knowledge on the specificities of exosomes and other types of extracellular vesicles, and their roles as important agents of cell-to-cell communication.
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              Reassessment of Exosome Composition

              The heterogeneity of small extracellular vesicles and presence of non-vesicular extracellular matter have led to debate about contents and functional properties of exosomes. Here, we employ high-resolution density gradient fractionation and direct immunoaffinity capture to precisely characterize the RNA, DNA, and protein constituents of exosomes and other non-vesicle material. Extracellular RNA, RNA-binding proteins and other cellular proteins are differentially expressed in exosomes and non-vesicle compartments. Argonaute 1–4, glycolytic enzymes and cytoskeletal proteins are absent from exosomes. We identify Annexin A1 as a specific marker for microvesicles that are shed directly from the plasma membrane. We further show that small extracellular vesicles are not vehicles of active DNA release. Instead, we propose a new model for active secretion of extracellular DNA through an autophagy- and multivesicular endosome-dependent, but exosome-independent mechanism. This study demonstrates the need for a reassessment of exosome composition and offers a framework for a clearer understanding of extracellular vesicle heterogeneity. A reassessment of exosome composition establishes the differential distribution of protein, RNA, and DNA between small extracellular vesicles and non-vesicular extracellular matter and establishes that small extracellular vesicles are not vehicles of active DNA release.
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                Author and article information

                Contributors
                Journal
                Small
                Small
                Wiley
                1613-6810
                1613-6829
                February 2024
                October 08 2023
                February 2024
                : 20
                : 7
                Affiliations
                [1 ] Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology 1277 Jiefang Avenue Wuhan 430022 China
                Article
                10.1002/smll.202307058
                37806763
                203d9994-e071-4555-b8f2-20c64cf79311
                © 2024

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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