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Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing

  • Author Footnotes
    1 Co-first authors.
    Nicholas S. Greaves
    Footnotes
    1 Co-first authors.
    Affiliations
    Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, UK

    The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK
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  • Author Footnotes
    1 Co-first authors.
    Kevin J. Ashcroft
    Footnotes
    1 Co-first authors.
    Affiliations
    Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, UK

    Inflammation Sciences Group, School of Translational Medicine, University of Manchester, Manchester, UK
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  • Mohamed Baguneid
    Affiliations
    The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK
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  • Ardeshir Bayat
    Correspondence
    Corresponding author at: Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology (MIB), 131 Princess Street, Manchester M1 7DN, UK. Tel.: +44 161 306 5177; fax: +44 161 306 5177.
    Affiliations
    Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, UK

    The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK

    Inflammation Sciences Group, School of Translational Medicine, University of Manchester, Manchester, UK

    Department of Plastic and Reconstructive Surgery, University Hospital South Manchester Foundation Trust, Wythenshawe Hospital, Manchester, UK
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  • Author Footnotes
    1 Co-first authors.

      Abstract

      Cutaneous wound healing ultimately functions to facilitate barrier restoration following injury-induced loss of skin integrity. It is an evolutionarily conserved, multi-cellular, multi-molecular process involving co-ordinated inter-play between complex signalling networks. Cellular proliferation is recognised as the third stage of this sequence. Within this phase, fibroplasia and angiogenesis are co-dependent processes which must be successfully completed in order to form an evolving extracellular matrix and granulation tissue. The resultant structures guide cellular infiltration, differentiation and secretory profile within the wound environment and consequently have major influence on the success or failure of wound healing. This review integrates in vitro, animal and human in vivo studies, to provide up to date descriptions of molecular and cellular interactions involved in fibroplasia and angiogenesis. Significant molecular networks include adhesion molecules, proteinases, cytokines and chemokines as well as a plethora of growth factors. These signals are produced by, and affect behaviour of, cells including fibroblasts, fibrocytes, keratinocytes, endothelial cells and inflammatory cells resulting in significant cellular phenotypic and functional plasticity, as well as controlling composition and remodelling of structural proteins including collagen and fibronectin. The interdependent relationship between angiogenesis and fibroplasia relies on dynamic reciprocity between cellular components, matrix proteins and bioactive molecules. Unbalanced regulation of any one component can have significant consequences resulting in delayed healing, chronic wounds or abnormal scar formation. Greater understanding of angiogenic and fibroplastic mechanisms underlying chronic wound pathogenesis has identified novel therapeutic targets and enabled development of improved treatment strategies including topical growth factors and skin substitutes.

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