It has been reported that hepatoma multicellular spheroid formation goes through three stages: 1) aggregate formation of dispersed cells via integrin (β1)-ECM (extracellular matrices: collagen, fibronectin, and laminin); 2) a delay phase of E-cadherin expression and accumulation; 3) formation of strong cell-cell contacts via homophilic cadherin-cadherin binding.[46,47,48,49] Even though fibrinogen moiety is present in modified PEG-based hydrogels containing PEGDA, the fibrinogen may not directly bind to integrin (α5β1) on hepatocytes. This evidence concerns the gene CDH17 and hepatocellular carcinoma.