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      Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing

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          Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications.

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          Most cited references 25

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          Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair.

          Cutaneous wounds persist as a health care crisis in spite of increased understanding of the cellular and molecular responses to injury. Contributing significantly to this crisis is the lack of reliable therapies for treatment of wounds that are slow to heal including chronic wounds and deep dermal wounds that develop hypertrophic scars. This article will review the growing evidence demonstrating the promise of multipotent mesenchymal stem/stromal (MSCs) for the treatment of impaired wound healing. MSCs are often referred to as mesenchymal stem cells despite concerns that these cells are not truly stem cells given the lack of evidence demonstrating self-renewal in vivo. Regardless, abundant evidence demonstrates the therapeutic potential of MSCs for repair and regeneration of damaged tissue due to injury or disease. To date, MSC treatment of acute and chronic wounds results in accelerated wound closure with increased epithelialization, granulation tissue formation and angiogenesis. Although there is evidence for MSC differentiation in the wound, most of the therapeutic effects are likely due to MSCs releasing soluble factors that regulate local cellular responses to cutaneous injury. Important challenges need to be overcome before MSCs can be used effectively to treat wounds that are slow to heal.
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            Dynamic reciprocity in the wound microenvironment.

            Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction among cells and their surrounding microenvironment. In this review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical, and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but also cellular differentiation, migration, proliferation, and survival during tissue development, including, e.g., embryogenesis, angiogenesis, as well as during pathologic processes including cancer, diabetes, hypertension, and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology may be understood within the DR framework. The implications of applying the principles of DR to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. © 2011 by the Wound Healing Society.
              • Record: found
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              Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds.

              Several growth factors are potential mediators of wound healing, although their actual roles, interactions, and therapeutic use are not established. Six well-characterized human growth factors were chosen for detailed investigation by topical application to standardized skin wounds in swine: epidermal growth factor (EGF), transforming growth factors alpha and beta (TGF-alpha and TGF-beta), fibroblast growth factor (FGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor (PDGF). When applied singly in doses up to 1,500 ng, only TGF-beta produced a marked tissue response, as demonstrated by an increase in the new connective tissue volume, the collagen content and maturity, and increased angiogenesis. However, TGF-beta enhanced inflammation and caused abnormal epithelial differentiation and decreased epithelial volume, the last reversed by addition of IGF-I. Recombinant PDGF-2 homodimer, if given in combination with recombinant IGF-I, caused a similar increase in the new connective tissue volume and collagen content and maturity, but without increased inflammation. In addition, this combination stimulated increased amounts of epithelium with normal differentiation. The synergy of PDGF-2 and IGF-I was optimal at a ratio of 2:1 by weight. Of the six individual factors and nine combinations tested, the combinations of PDGF-2 and IGF-I or PDGF-2 and TGF-alpha were the most potent stimulators of healing in the absence of increased inflammation.

                Author and article information

                Int Wound J
                Int Wound J
                International Wound Journal
                Blackwell Publishing Ltd (Oxford, UK )
                October 2013
                01 August 2013
                : 10
                : 5
                : 493-500
                [1 ]MiMedx Group, Inc. Marietta, GA, USA
                [2 ]Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine Palo Alto, CA, USA
                [3 ]Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology Atlanta, GA, USA
                [4 ]The Angiogenesis Foundation Cambridge, MA, USA
                Author notes
                Correspondence to Thomas J Koob, MiMedx Group, Inc., 1775 West Oak Commons Ct., Marietta, GA 30062, USA, E-mail: TKoob@ 123456mimedx.com
                ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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