Evaluation of Anti-Fibrotic Therapeutics Using a Three-Dimensional In Vitro Liver Fibrosis Model

Abstract

SCIENTIFIC LANGUAGEThree dimensional (3D) bioprinting is a leading technology in tissue engineering that offers controlled deposition of cells and bioinks layer by layer, this technique allows for the accurate replication of tissue spatial organization, incorporating tissue compartmentalization and vascularization. This study focuses on the screening of anti-fibrotic drug on a previously established 3D liver diseased model. In market, there are no available 3D in vitro liver disease model that is used for liver regeneration/drug screening. The 3D in vitro liver disease was fabricated by utilizing decellularized rat liver Extracellular Matrix (dECM) and Gelatin Methacryl (GelMA) along with hepatic cells. The developed healthy model was rendered fibrotic by employing methotrexate (MTX) a fibrotic agent at a concentration of 10mM for 72 hours. MTX is well known to cause hepatotoxicity and have been analysed for causing fibrotic -like characteristic in the model. This manuscript mainly focuses on the reversal aspect of the study, where anti-fibrotic drug, aspirin was administered on the fibrotic model to evaluate the effect. This study examines the impact of antifibrotic drug aspirin (ASP) on both 2D HepG2 cell and the fabricated 3D model by integrating major experiments including the biochemical, morphological, and molecular analyses. The outcomes disclose a progressive decline in the fibrotic trait and regaining the hepatocyte-specific functionality. Successful employment of this 3D model will reduce the involvement of animals in drug testing experiments.