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      Wound dressings incorporating microRNAs: Innovative therapy for diabetic wound treatment

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          Abstract

          Diabetic wounds are the most critical complication in patients with diabetes, which often lead to hospitalization and limb amputations. Diabetic foot ulcers (DFU) is characterized by infections, prolonged inflammation, and a delayed wound healing process. Different types of medical procedures including surgical therapy, drug delivery, stem cell therapy, and wound dressings are used to manage DFU. Bioactive dressings such as hydrogels, nanofiber, and collagens are promising materials that can accelerate the healing process. The wound dressing materials can also be loaded with bioactive molecules like nucleic acids. MicroRNAs (miRNAs) are small non-coding RNA molecules that have recently emerged as regulators of impaired wound healing and could be a target for DFU treatment. miRNA therapeutics can be delivered to the wound region using different delivery systems such as exosomes and nanoparticles. These wound dressings have a high potential for treating diabetic wounds by topical delivery of certain miRNAs in a sustained release manner.

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          Most cited references19

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          Wound Healing: A Cellular Perspective

          Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. With the evolution of single cell technologies, it has been possible to uncover phenotypic and functional heterogeneity within several of these cell types. There have also been discoveries of rare, stem cell subsets within the skin, which are unipotent in the uninjured state, but become multipotent following skin injury. Unraveling the roles of each of these cell types and their interactions with each other is important in understanding the mechanisms of normal wound closure. Changes in the microenvironment including alterations in mechanical forces, oxygen levels, chemokines, extracellular matrix and growth factor synthesis directly impact cellular recruitment and activation, leading to impaired states of wound healing. Single cell technologies can be used to decipher these cellular alterations in diseased states such as in chronic wounds and hypertrophic scarring so that effective therapeutic solutions for healing wounds can be developed.
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            The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

            Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds.
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              Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies

              Normal wound healing is a dynamic and complex multiple phase process involving coordinated interactions between growth factors, cytokines, chemokines, and various cells. Any failure in these phases may lead wounds to become chronic and have abnormal scar formation. Chronic wounds affect patients’ quality of life, since they require repetitive treatments and incur considerable medical costs. Thus, much effort has been focused on developing novel therapeutic approaches for wound treatment. Stem-cell-based therapeutic strategies have been proposed to treat these wounds. They have shown considerable potential for improving the rate and quality of wound healing and regenerating the skin. However, there are many challenges for using stem cells in skin regeneration. In this review, we present some sets of the data published on using embryonic stem cells, induced pluripotent stem cells, and adult stem cells in healing wounds. Additionally, we will discuss the different angles whereby these cells can contribute to their unique features and show the current drawbacks.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                IJBMS
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                September 2022
                : 25
                : 9
                : 1042-1044
                Affiliations
                [1 ] Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran
                [2 ] Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
                Author notes
                [* ]Corresponding author: Mohammad Hasan Soheilifar. Yara Institute, Academic Center for Education, Culture and Research (ACECR), Enghelab St, Tehran, Iran. Tel: +989359001066; Email: Soheilih@gmail.com
                Article
                10.22038/IJBMS.2022.67236.14739
                9526883
                c01ef7cc-e718-4b0b-9b38-f5653f513d46

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 August 2022
                : 30 August 2022
                Categories
                Letter to Editor

                diabetic foot,dressings,microrna,wound healing,wound therapy

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