Three-dimensional biomimetic hepatic models for in vitro drug screening for hepatotoxicity

The major focus of the thesis is to develop a hydrogel that can mimic the native microenvironment that is present in the liver tissue. The decellularized liver matrix (DLM) retains the biochemical cues from the native tissue and has the potential to maintain the liver-specific functions. The thesis also explores the influence of DLM in altering the response of cells towards drugs. The DLM was further modified with the addition of galactose to increase the liver-specific functions. A major phenomenon in the liver is the metabolic zonation, where the hepatocytes exhibit spatial heterogeneity in terms of their function. The in house developed mini bioreactor showed the formation of oxygen and metabolic gradients and also exhibited a pattern of centrilobular necrosis on treatment with acetaminophen.