The extracellular matrix (ECM) in the liver as well as in many organs comprises a peripheral network linking numerous macromolecules typically classified into collagens, microfibrillar proteins, proteoglycans, chemokines, growth factors and glycoproteins. In addition to its role as an essential structural and physiological component, it plays a vital role in driving key cellular events such as cell adhesion, migration, proliferation, differentiation and survival. Any structural inherited or acquired defect and/or metabolic or pathologic alteration in the hepatic ECM may cause cellular and organ responses leading to the development or progression of liver disease. Therefore, the ECM molecules are key players in tissue engraftment and in the pathophysiology of liver disease. In this review we provide a snapshot on current efforts for understanding its role in physiological and non-physiological states, by describing how tissue engineering platforms can enhance in vitro and in vivo models of liver disease, by providing examples where bioengineered ECM can serve as systems biology approaches to study the ECM, and then by evaluating pathological protein regulatory networks in the liver using systems biology tools. These approaches hold great promise for future research.
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