Growth factor regulation and manipulation in wound repair: to scar or not to scar, that is the question

Abstract

The process of tissue repair following injury is in the large part mediated by secreted growth factors which, in an autocrine or paracrine fashion, stimulate immune and mesenchymal cells at the site of injury. The complex process of replacing damaged tissue with newly formed tissue involves components of the blood, coagulation, immune and mesenchymal systems as well as cytokines, chemokines, metalloproteinases and growth factors. This review will focus on growth factors as the controllers of this process and includes members of the transforming growth factor (TGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), connective tissue derived growth factor (CTGF) and insulin-like growth factor-I (IGF-I) families of growth factors. These growth factors stimulate re-epithelialisation, angiogenesis, extracellular matrix (ECM) formation and cell proliferation each of which plays a role in tissue replacement and restoration of tissue function following injury. Normal wound healing frequently involves the formation of scar tissue, including increased mesenchymal cell proliferation and excessive production of ECM proteins. While scar tissue rapidly and effectively closes wounds, it leaves visually apparent tissue structure changes and may reduce the function of the tissue leading to compromised organ function. Growth factors, the conductors of these processes, are targets for therapeutic manipulation of wound healing and scar formation. Recent patents involving growth factors may be implicated in the treatment of wound healing following tissue injury. Enhanced growth factor activity may be beneficial to increase the rate of wound healing in chronic non-healing wounds, whereas reduction of growth factor presence or activity may reduce scar formation in the skin and internal organs, which may be particularly relevant where scar formation is associated with pathologic loss of life sustaining organ function.

• fibroproliferation
• growth factors
• pulmonary fibrosis
• wound healing