Shaping Tomorrow's Liver Organoids: A Journey Toward Integrating Bile Ducts

Abstract

AbstractLiver tissue engineering has undergone remarkable developments since the late 20th century, transitioning from simple two‐dimensional cultures to sophisticated three‐dimensional organoid models for drug toxicity assessments. Stem cell innovations have enabled the creation of liver organoids for disease modelling and tissue engineering. However, a key limitation is the absence of functional bile ducts in these organoids, crucial for replicating bile‐duct related diseases. Bile, synthesized by hepatocytes, plays a vital role in digesting fats and expelling lipid‐soluble wastes, including drug byproducts. Diseases impeding bile flow are responsible for many liver transplants and can cause severe conditions such as liver cirrhosis, causing over 50,000 annual deaths in the US. Current liver organoids, while bile‐producing, are devoid of bile ducts, limiting their efficacy in mimicking diseases related to bile flow. This article underscores the pressing need to incorporate bile ducts in engineered liver tissues, delves into the challenges faced in this effort, and highlights potential solutions through biomaterial and bioengineering techniques. Such advancements will offer researchers enhanced insights into bile duct disorders and pave the way for exploring innovative therapeutic strategies.