Extracellular matrix hydrogels from decellularized tissues: structure and function

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discusse

Perspective: The Mechanobiology of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second most deadly primary cancer in the world and is thus a major global health challenge. HCC primarily develops in patients with an underlying chronic liver disease, the vast majority with advanced cirrhosis, characterized by increased matrix deposition and liver stiffness. Liver stiffness is highly associated with cancer development and poor patient outcome and is measured clinically to assess cancer risk; cirrhotic livers greatly exceed the threshold stiffness shown to alter hepatocyte cell behavior and to increase the malignancy of cancer cells. Recent studies have shown that cirrhotic liver cells have highly irregular nuclear morphologies and that nuclear deformation mediates mechanosensitive signaling. Separate research has shown that nuclear deformation can increase genetic instability and the accumulation of DNA damage in migrating cancer cells. We hypothesize that the mechanical changes associated with chronic liver disease are drivers of oncogenesis, activating mechanosensitive signaling pathways, increasing rates of DNA damage, and ultimately inducing malignant transformation