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      Keloids: Current and emerging therapies

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          Abstract

          Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types.

          Lay Summary

          Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.

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          Most cited references189

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          A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods

          The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions.
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            International clinical recommendations on scar management.

            Many techniques for management of hypertrophic scars and keloids have been proven through extensive use, but few have been supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article reports a qualitative overview of the available clinical literature by an international panel of experts using standard methods of appraisal. The article provides evidence-based recommendations on prevention and treatment of abnormal scarring and, where studies are insufficient, consensus on best practice. The recommendations focus on the management of hypertrophic scars and keloids, and are internationally applicable in a range of clinical situations. These recommendations support a move to a more evidence-based approach in scar management. This approach highlights a primary role for silicone gel sheeting and intralesional corticosteroids in the management of a wide variety of abnormal scars. The authors concluded that these are the only treatments for which sufficient evidence exists to make evidence-based recommendations. A number of other therapies that are in common use have achieved acceptance by the authors as standard practice. However, it is highly desirable that many standard practices and new emerging therapies undergo large-scale studies with long-term follow-up before being recommended conclusively as alternative therapies for scar management.
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              Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management.

              Hypertrophic scars and keloids result from an abnormal fibrous wound healing process in which tissue repair and regeneration-regulating mechanism control is lost. These abnormal fibrous growths present a major therapeutic dilemma and challenge to the plastic surgeon because they are disfiguring and frequently recur. To provide updated clinical and experimental information on hypertrophic scars and keloids so that physicians can better understand and properly treat such lesions. A Medline literature search was performed for relevant publications and for diverse strategies for management of hypertrophic scars and keloids. The growing understanding of the molecular processes of normal and abnormal wound healing is promising for discovery of novel approaches for the management of hypertrophic scars and keloids. Although optimal treatment of these lesions remains undefined, successful healing can be achieved only with combined multidisciplinary therapeutic regimens.
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                Author and article information

                Journal
                Scars Burn Heal
                Scars Burn Heal
                SBH
                spsbh
                Scars, Burns & Healing
                SAGE Publications (Sage UK: London, England )
                2059-5131
                10 August 2020
                Jan-Dec 2020
                : 6
                : 2059513120940499
                Affiliations
                [1 ]Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Bridgetown, Barbados, West Indies
                [2 ]Pine Medical Centre, 3rd Avenue Belleville, St. Michael, Barbados, West Indies
                Author notes
                [*]Nkemcho Ojeh, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, P.O. Box 64, St. Michael, Bridgetown BB, 11000, Barbados, West Indies. Email: nkemcho.ojeh@ 123456cavehill.uwi.edu
                Author information
                https://orcid.org/0000-0002-2507-2209
                Article
                10.1177_2059513120940499
                10.1177/2059513120940499
                7418256
                d9b1228e-270d-42e1-8076-2e22f5be65ca
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Categories
                Review
                Custom metadata
                January-December 2020
                ts1

                keloids,scar,recurrence,wound healing,treatment,management
                keloids, scar, recurrence, wound healing, treatment, management

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