Table 1.

Components of the ECM, their structure, function and significance to tissue engineering.

ECM component	Structure	Function	Importance to tissue engineering
Collagens	Formed as fibrils within the ECM (Types I, II, III, V and XI)	Provide tensile strengthInfluence cell processes, for example, adhesion and migration	Collagen type I is often used as a coating on gel scaffolds to promote cell adhesion, in addition to its ability to stimulate myogenic and osteogenic differentiation of stem cells6Also frequently used as scaffold material for cells11,12 both as a single material and within a composite scaffold. As a natural material, it seldom initiates an inflammatory response from the host
Elastin	Composed of single tropoelastin subunits cross-linked with an outer layer of fibrillin microfibrils making up an elastic fibre	Closely linked to collagensAllows tissues such as the skin and tendon to recover/recoil	Being investigated as a biomaterial for use in tissue engineering, particularly in vascular tissue engineering due to its importance in blood vessels13
Fibronectin	Two forms either plasma (within blood) or cellular protein (created by fibroblasts)Arranged into a mesh of fibrils similar to collagen and is linked to cell surface receptors (integrins)	Found in the basement membrane of the ECMPlays a role in cell adhesion, embryonic development and the healing process following wound injury	Importance of fibronectin in embryonic development and wound healing demonstrate that it needs to play a key role in tissue engineering applications. Especially, the RGD sequence that is critical in ensuring cell adhesion, transforming substrates allowing for cell attachment14,15
Laminins	Laminins are another type of glycoprotein, with a trimeric structure. They are made up of three different chains, α, β and γ which exist in various genetically distinct forms	Reside in the basement membraneExpressed by various tissue types including both muscle and epithelial cellsPlay a vital part in several cell processes including differentiation and migration via their integrins	Similarly to fibronectin, laminins have the capacity for cell binding and are another option to be used to enhance cell adhesion in culture conditions16
Tenascins	Tenascins are a group of ECM proteins and exist as five different manifestations, TN-C, TN-R, TN-W, TN-X and TN-Y	Linked to mechanical activityTypically found within connective tissues where load bearing is required, although they also occur within the skin and brain	During embryonic development and tissue repair, TN-C is highly expressed, it is also typically found within stem cell niches. However, it prevents cell adhesion when used as a protein coating for cell culture substrates17
Growth factors	Tied to the ECM through either heparan or heparan sulphate	They can be linked to tissues with their names. For example, vascular endothelial growth factor stimulates the formation of blood vesselsTriggered into action by a variety of processes (not necessarily in a soluble form) including wound healing and tissue remodelling	Multiple growth factors demonstrated as being crucial to development and differentiation of many tissues. Their use is being explored within tissue engineering, for example, improving wound healing of tendon tissue18
MMPs	Structure occurs as zinc-dependent endopeptidases19	Capable of disintegrating the ECM, associated with many different processes including angiogenesis and wound repair	MMPs are key modulators for tissue remodelling; their expression can be useful indicators of cellular behaviour for tissue engineering investigations

ECM: extracellular matrix; MMP: matrix metalloproteinase.