Abstract
Chronic wounds develop when the orderly process of cutaneous wound healing is delayed or disrupted. Development of a chronic wound is associated with significant morbidity and financial burden to the individual and health-care system. Therefore, new therapeutic modalities are needed to address this serious condition. Mesenchymal stem cells (MSCs) promote skin repair, but their clinical use has been limited due to technical challenges. Extracellular vesicles (EVs) are particles released by cells that carry bioactive molecules (lipids, proteins, and nucleic acids) and regulate intercellular communication. EVs (exosomes, microvesicles, and apoptotic bodies) mediate key therapeutic effects of MSCs. In this review we examine the experimental data establishing a role for EVs in wound healing. Then, we explore techniques for designing EVs to function as a targeted drug delivery system and how EVs can be incorporated into biomaterials to produce a personalized wound dressing. Finally, we discuss the status of clinically deploying EVs as a therapeutic agent in wound care.
Highlights
Cutaneous wound healing is complex, consisting of overlapping processes: hemostasis/coagulation, inflammation, proliferation, and remodeling [1]
Extracellular vesicles (EVs) were enriched in miR-21, miR-23a, miR-125b, and miR-145. miRNA delivery reduced TGF-β/SMAD2 signaling in fibroblasts
Mesenchymal stem cells (MSCs) were shown to delay the rejection of MHC-mismatched skin grafts in immunocompetent baboons [212]. These findings indicate that MSC-EVs could be an adjuvant therapy when using allografts to reduce immune-mediated graft rejection
Summary
Cutaneous wound healing is complex, consisting of overlapping processes: hemostasis/coagulation, inflammation, proliferation, and remodeling [1]. This requires intercellular communication among resident cells and entering immune cells through soluble, membrane-bound, and extracellular matrix (ECM) molecules [1,2]. Risk factors for the development of chronic wounds include advanced age, diabetes mellitus with associated peripheral vascular disease and peripheral neuropathy, as well as chronic kidney disease and immobility [5,7]. Current advanced therapies, including topical application of growth factors [8], extracellular matrix products [9], and skin substitutes [10], are not always effective [11]. It is imperative that cutting-edge therapeutics be identified to treat chronic wounds
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