Interactions Between Extracellular Matrix and Growth Factors in Wound Healing

Wound Repair Regen. Mar-Apr 2009;17(2):153-62. doi: 10.1111/j.1524-475X.2009.00466.x.


Dynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor-2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor-induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet-derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin-C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor-beta also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chronic Disease
  • Collagen / physiology
  • Elastin / physiology
  • Extracellular Matrix / physiology*
  • Fibroblast Growth Factor 2 / physiology
  • Fibroblasts / physiology
  • Glycosaminoglycans / physiology
  • Humans
  • Integrins / physiology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Matrix Metalloproteinases / physiology
  • Membrane Glycoproteins / physiology
  • Osteonectin / physiology
  • Receptors, Cell Surface / physiology
  • Thrombospondins / physiology
  • Wound Healing / physiology*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / physiopathology*
  • Wounds and Injuries / therapy


  • Glycosaminoglycans
  • Integrins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Osteonectin
  • Receptors, Cell Surface
  • Thrombospondins
  • Fibroblast Growth Factor 2
  • Collagen
  • Elastin
  • Matrix Metalloproteinases