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      Challenges in the Treatment of Chronic Wounds

      * ,

      Advances in Wound Care

      Mary Ann Liebert, Inc.

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          Abstract

          Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients.

          Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing.

          Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based.

          Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

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          Most cited references 254

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          Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

          Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging.
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            Vacuum-assisted closure: a new method for wound control and treatment: clinical experience.

            Despite numerous advances, chronic and other difficult-to-manage wounds continue to be a treatment challenge. Presented is a new subatmospheric pressure technique: vacuum-assisted closure (The V.A.C.). The V.A.C. technique entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure (125 mmHg below ambient pressure). Three hundred wounds were treated: 175 chronic wounds, 94 subacute wounds, and 31 acute wounds. Two hundred ninety-six wounds responded favorably to subatmospheric pressure treatment, with an increased rate of granulation tissue formation. Wounds were treated until completely closed, were covered with a split-thickness skin graft, or a flap was rotated into the health, granulating would bed. The technique removes chronic edema, leading to increased localized blood flow, and the applied forces result in the enhanced formation of granulation tissue. Vacuum-assisted closure is an extremely efficacious modality for treating chronic and difficult wounds.
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              Concise review: role of mesenchymal stem cells in wound repair.

              Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes. Recent studies revealed that human placental membranes are a rich source of MSCs for tissue regeneration and repair. This review provides a concise summary of current knowledge of biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role MSCs have in each phase of the wound-healing process. In addition, characterization of MSCs containing skin substitutes is described, demonstrating the presence of key growth factors and cytokines uniquely suited to aid in wound repair.
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                Author and article information

                Journal
                Adv Wound Care (New Rochelle)
                Adv Wound Care (New Rochelle)
                wound
                Advances in Wound Care
                Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                2162-1918
                2162-1934
                01 September 2015
                01 September 2015
                : 4
                : 9
                : 560-582
                Affiliations
                Phoenix VA Health Care System , Phoenix, Arizona.
                Author notes
                [ * ]Correspondence: Phoenix VA Health Care System, 650 East Indian School Road, Phoenix, AZ 85012 (e-mail: robert.frykberg@ 123456va.gov ).
                Article
                10.1089/wound.2015.0635
                10.1089/wound.2015.0635
                4528992
                26339534
                Copyright 2015, Mary Ann Liebert, Inc.© Robert G. Frykberg and Jaminelli Banks 2015; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                Page count
                Figures: 5, Tables: 3, References: 297, Pages: 23
                Product
                Categories
                Comprehensive Invited Review

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