Adult & Umbilical Cord Stem Cell Research (Ethical)

Wound Healing: Extracellular Matrix (ECM)


The extracellular matrix (ECM) is a complex structural entity surrounding and supporting cells that are found within mammalian tissues. The ECM is often referred to as the connective tissue.

The ECM is composed of 3 major classes of biomolecules:

1. Structural proteins: collagen and elastin.

2. Specialized proteins: e.g. fibrillin, fibronectin, and laminin.

3. Proteoglycans: these are composed of a protein core to which is attached long chains of repeating disaccharide units termed of glycosaminoglycans (GAGs) forming extremely complex high molecular weight components of the ECM. Proteoglycans are covered in the section on Glycosaminoglycans and Proteoglycans.

Key Points

   1. The extracellular matrix (ECM) is the largest component of normal skin and gives the skin its unique properties of elasticity, tensile strength and compressibility.
   2. In acute wounds the provisional wound matrix, containing fibrin and fibronectin, provides a scaffolding to direct cells into the injury, as well as stimulating them to proliferate, differentiate and synthesise new ECM.
   3. Chronic wounds contain increased levels of inflammatory cells, giving rise to elevated levels of proteases that appear to degrade the ECM components, growth factors and receptors that are essential for healing.
   4. Understanding of the importance of re-establishing a functional ECM in chronic wounds has led to technical advances and the development of products that reduce excessive protease levels or contribute functional ECM proteins, thereby facilitating the healing process.


The extracellular matrix (ECM) is the largest component of the dermal skin layer and the synthesis of ECM is a key feature of wound healing, especially when there has been a significant loss of tissue that precludes closure by primary intention. This article discusses the proteins contained in the ECM of normal skin that are important in the healing of acute and chronic wounds. In addition, the theory that the high levels of proteases found in chronic wounds impair healing by degrading essential components of the ECM is discussed using data from cell culture experiments and immunohistochemical analyses of wound biopsies.

As a consequence of this theory new dressings have been developed that are designed to reduce protease levels in wound fluids by providing a competitive substrate (collagen) for the proteases and thereby reducing proteolytic destruction of essential ECM components (fibronectin) and platelet-derived growth factors (PDGFs).

Other new approaches include the topical treatment of chronic wounds with agents that reduce the synthesis of matrix metalloproteinases (MMPs), such as a mixture of metal cations, and treatment with unique proteins (amelogenin) to replace the corrupted ECM.

Clinical and laboratory data now clearly show that components of the ECM play an important role in normal wound healing and that the destruction of ECM components impairs healing. This has lead to the development of new therapies that aim to reduce the destruction of ECM or re-establish undamaged ECM.

The extracellular matrix of normal skin

The largest component of normal skin is the ECM, a gel-like matrix produced by the cells that it surrounds (Figure 1).

The ECM is composed of a variety of polysaccharides, water and collagen proteins which give the skin remarkable properties [1], [2].

On a weight basis, the tensile (breaking) strength of normal skin approaches that of steel, yet skin also has substantial elasticity and compressibility. These properties are due to the combination of two main classes of ECM molecules, which are secreted by fibroblasts and epidermal cells. They are:

    * Fibrous structural proteins, including collagens, elastin and laminin, which give the ECM strength and resilience

    * Proteoglycans, such as dermatan sulfate and hyaluronan, typically consist of multiple glycosaminoglycan chains (formed from repeating disaccharide units) that branch from a linear protein core. Extracellular proteoglycans are large, highly hydrated molecules that help cushion cells in the ECM.
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Images for ECM (for reports, etc)

Keywords: extracellular matrix (ECM); acute wounds; chronic wounds; proteoglycans; glycosaminoglycans; metalloproteinases; chemokines; wound bed preparation; wound dressings.