Current advances and prospects in biomaterials-guided tools for liver organoids research

Liver is the largest solid organ in the human body engaged in an array of critical physiological activities that primarily support metabolism, digestion, nutrient storage, detoxification. Liver dysfunction due to disease or surgical intervention often leads to severe life-threatening complications or death in humans. Therefore, in vitro liver models that mimic key functional characteristics are considered a reliable option for the study of liver diseases and the development of new therapeutic agents. Furthermore, they can overcome the limitations of conventional monolayer cultures and animal related experiments in assessing the response of new therapeutic agents and drug molecules. In recent years, the emergence and advancement of organoid technology has greatly facilitated the development of reliable in vitro liver models for a variety of biomedical and pharmacological applications. However, organoid culture primarily relies on tumor-derived extracellular matrix, such as Matrigel, which pose challenges due to its xenogeneic nature and variable composition. Therefore, creating organoid models using Matrigel-free hydrogel materials could significantly improve the outcomes of regenerative medicine and experimental studies. In this review, we provide an overview of rapidly evolving biomaterials for organoid research. We then outline preparation methods and the most relevant studies applying different hydrogels for engineering liver organoid models. Finally, we discuss the challenges, future perspectives, and opportunities of hydrogels in engineering next-generation liver organoid models for translational applications.