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      Genomic and Proteomic Evaluation of Tissue Quality of Porcine Wounds Treated With Negative Pressure Wound Therapy in Continuous, Noncontinuous, and Instillation Modes

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          Abstract

          Objective: Negative pressure wound therapy with instillation (NPWTi-d) combines NPWT with automated delivery and removal of topical wound treatment solutions. This porcine study compared genomic and proteomic responses of wounds treated with NPWTi-d with saline to wounds treated with NPWT in continuous and noncontinuous modes. Methods: Full-thickness porcine dorsal excisional wounds were treated with continuous NPWT, intermittent NPWT, dynamic NPWT, or NPWTi-d with saline (n = 10 wounds per group). On day 7, animals were euthanized and tissues collected. Real-time quantitative polymerase chain reaction arrays profiled expression of 84 genes including extracellular matrix remodeling factors, inflammatory cytokines and chemokines, and growth factors and major signaling molecules. Concentrations of proteins associated with angiogenesis, extracellular matrix components, and cellular energetics were analyzed via enzyme-linked immunosorbent assays. Results: Gene expression profiles for NPWTi-d with saline and continuous NPWT were similar. There were 5 upregulated and 18 downregulated genes overexpressed in NPWTi-d compared to NPWT wounds. Protein content was comparable in all treatment groups and similar to unwounded tissue. Conclusions: Previous preclinical studies have reported an increased rate of granulation tissue formation with NPWTi-d with saline compared to NPWT in continuous and noncontinuous modes. This evaluation of gene and protein expression suggests that the granulation tissue in these wounds has a similar quality. This first look at the differences in gene expression, particularly in genes related to remodeling, cell adhesion, inflammation, and growth factors, could help to clarify the observed differences in granulation rates.

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          Wound healing: an overview of acute, fibrotic and delayed healing.

          Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.
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            Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial.

            Diabetic foot wounds, particularly those secondary to amputation, are very complex and difficult to treat. We investigated whether negative pressure wound therapy (NPWT) improves the proportion and rate of wound healing after partial foot amputation in patients with diabetes. We enrolled 162 patients into a 16-week, 18-centre, randomised clinical trial in the USA. Inclusion criteria consisted of partial foot amputation wounds up to the transmetatarsal level and evidence of adequate perfusion. Patients who were randomly assigned to NPWT (n=77) received treatment with dressing changes every 48 h. Control patients (n=85) received standard moist wound care according to consensus guidelines. NPWT was delivered through the Vacuum Assisted Closure (VAC) Therapy System. Wounds were treated until healing or completion of the 112-day period of active treatment. Analysis was by intention to treat. This study has been registered with , number NCT00224796. More patients healed in the NPWT group than in the control group (43 [56%] vs 33 [39%], p=0.040). The rate of wound healing, based on the time to complete closure, was faster in the NPWT group than in controls (p=0.005). The rate of granulation tissue formation, based on the time to 76-100% formation in the wound bed, was faster in the NPWT group than in controls (p=0.002). The frequency and severity of adverse events (of which the most common was wound infection) were similar in both treatment groups. NPWT delivered by the VAC Therapy System seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care.
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              Chemokines in cutaneous wound healing.

              Healing of wounds is one of the most complex biological events after birth as a result of the interplay of different tissue structures and a large number of resident and infiltrating cell types. The latter are mainly constituted by leukocyte subsets (neutrophils, macrophages, mast cells, and lymphocytes), which sequentially infiltrate the wound site and serve as immunological effector cells but also as sources of inflammatory and growth-promoting cytokines. Recent data demonstrate that recruitment of leukocyte subtypes is tightly regulated by chemokines. Moreover, the presence of chemokine receptors on resident cells (e.g., keratinocytes, endothelial cells) indicates that chemokines also contribute to the regulation of epithelialization, tissue remodeling, and angiogenesis. Thus, chemokines are in an exclusive position to integrate inflammatory events and reparative processes and are important modulators of human-skin wound healing. This review will focus preferentially on the role of chemokines during skin wound healing and intends to provide an update on the multiple functions of individual chemokines during the phases of wound repair.
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                Author and article information

                Journal
                Eplasty
                Eplasty
                ePlasty
                Eplasty
                Open Science Company, LLC
                1937-5719
                2014
                4 December 2014
                : 14
                : e43
                Affiliations
                [1] aInnovation and Strategic Marketing, Kinetic Concepts, Inc, San Antonio, Tex
                [2] bScientific Affairs, KCI Medical Ltd, Dublin, Ireland, UK
                Author notes
                Article
                43
                4258932
                25525482
                bc70a0d9-367a-4743-9e9c-f2a8c46e944f
                Copyright © 2014 The Author(s)

                This is an open-access article whereby the authors retain copyright of the work. The article is distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Journal Article

                Surgery
                genomics,proteomics,negative-pressure wound therapy,hypertonic saline solution,instillation

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