Review article
Growth factors in wound healing

https://doi.org/10.1016/S0039-6109(02)00202-5Get rights and content

Section snippets

Inflammatory phase

When the integrity of human skin is broken and capillaries and other vessels are sheared, there is an extravasation of blood and blood products into the site of disruption. Here, blood coagulates and platelets aggregate, forming a fibrin-rich plug. This plug helps prevent further loss of blood from vessels and forms a barrier against contamination from invading microbes. It also marks the first stage of tissue repair in that it serves as a provisional matrix, a foundation on which wound healing

Proliferative phase

In contrast to neutrophils, monocytes, in response to monocyte-specific chemoattractants, continue to migrate into the wound long after the initial stages of healing. When present in the tissue, they become activated to macrophages. These macrophages begin producing their own growth factors, including PDGF, TGF-α, TGF-β, IGF-1, VEGF, and tumor necrosis factor (TNF)-α [2], [9], which, along with the growth factors produced by damaged parenchymal cells and the stored growth factors that are

Remodeling phase

The final stage of wound healing begins while tissue proliferation is still occurring. Reduced concentrations of growth factors involved in earlier phases of wound healing and the increased expression of others, including high levels of TGF-β1, initiate the differentiation of fibroblasts into myofibroblasts, cells that contain increased numbers of actin filaments [11]. The importance of these cells stems from their contractile ability. The lattice-like structure of the newly deposited ECM is

Growth factors

There are five known superfamilies of growth factors. The growth factors, along with their receptors, vary in structure and cell pathway activation between families and within each family. Still, some consistencies exist. Most growth factors originate from large proteins or multiple gene products and undergo posttranslational modification before being released in an active state [13]. Growth factor receptors are transmembrane glycoproteins whose effects are seen largely through kinase domains

Treatment strategies

The reason for the disappointing results in growth factor clinical trials to date is undoubtedly multifactorial. The success of recombinant PDGF-B in the form of becaplermin (Regranex) cannot be overlooked, however, given the severity of the problem of diabetic ulcers and the conclusiveness of the large clinical trials. This study has set the standard for clinical trials of growth factors in wound healing and should make it easier for researchers in the future to create a suitable study design

Future directions

Chronic wounds are an ever-increasing problem. Approximately 1.5% of the population has a chronic wound at any given time [59], and this number will rise as medicine is able to support a growing number of aged and debilitated patients. Currently, most treatment strategies for chronic wounds employ techniques that have varied little over the course of the past century and that are relatively ineffective at bringing difficult wounds to a rapid closure. In the 1980s and 1990s, research on growth

First page preview

First page preview
Click to open first page preview
View PDF

References (60)

  • N. Vaisman et al.

    Characterization of the receptors for vascular endothelial growth factor

    J Biol Chem

    (1990)
  • J. Plouet et al.

    Characterization of the receptor to vasculotropin on bovine adrenal cortex-derived capillary endothelial cells

    J Biol Chem

    (1990)
  • M. Brauchle et al.

    Ultraviolet B and H2O2 are potent inducers of vascular endothelial growth factor expression in cultured keratinocytes

    J Biol Chem

    (1996)
  • H.D. Beer et al.

    Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair

    JID Symp Proc

    (2000)
  • L. Zhang et al.

    Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: an approach to gene therapy of skin aging and other diseases

    Biochem Biophys Res Commun

    (1996)
  • A.V. Titomirov et al.

    In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA

    Biochem Biophys Acta

    (1991)
  • S.A. Eming et al.

    Particle-mediated gene transfer of PDGF isoforms promotes wound repair

    J Invest Dermatol

    (1999)
  • D.L. Steed

    Modifying the wound healing response with exogenous growth factors

    Clin Plast Surg

    (1998)
  • V. Moulin

    Growth factors in skin wound healing

    Eur J Cell Biol

    (1995)
  • J. Ansel et al.

    Cytokine modulation of keratinocyte cytokines

    J Invest Dermatol

    (1990)
  • F. Grinnell

    Wound repair, keratinocyte activation and integrin modulation

    J Cell Sci

    (1992)
  • C.P. Kiritsy et al.

    Role of growth factors in cutaneous wound healing: a review

    Crit Rev Oral Biol Med

    (1993)
  • R.A.F. Clark

    Wound repair: overview and general considerations

  • A. Desmouliere et al.

    Transforming growth factor beta-1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts

    J Cell Biol

    (1993)
  • N.T. Bennet et al.

    Growth factors and wound healing: biochemical properties of growth factors and their receptors

    Am J Surg

    (1993)
  • R. Ross et al.

    A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro

    Proc Natl Acad Sci USA

    (1974)
  • G.F. Pierce et al.

    Role of platelet-derived growth factor in wound healing

    J Cell Biochem

    (1991)
  • G.H. Rudkin et al.

    Growth factors in surgery

    Plast Reconstr Surg

    (1996)
  • W.J. LaRochelle et al.

    PDGF-D, a new protease-activated growth factor

    Nat Cell Biol

    (2001)
  • G.F. Pierce et al.

    Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-β1 therapy

    J Lab Clin Med

    (1991)

    • Cited by (98)

    View all citing articles on Scopus
    View full text
    Copyright © 2003 Elsevier Inc. All rights reserved.