Recent Advances in Three-Dimensional In Vitro Models for Studies of Liver Fibrosis

Area of Science:

• Hepatology
• Regenerative Medicine
• Biomaterials

Background:

• Liver fibrosis affects over 1.5 billion people globally, characterized by excessive extracellular matrix deposition due to chronic liver injury.
• Progression to cirrhosis and cancer is common, necessitating a deeper understanding of its complex cellular and pathogenic mechanisms.
• Three-dimensional (3D) in vitro platforms are being developed to better model liver fibrosis progression.

Purpose of the Study:

• To review the pathophysiology of liver fibrosis.
• To highlight advancements in 3D in vitro liver models for studying fibrosis.
• To assess the biological relevance and fibrotic recapitulation capacity of these models.

Main Methods:

• Review of existing literature on liver fibrosis pathophysiology.
• Analysis of various 3D in vitro liver models: spheroids, organoids, assembloids, bioprinted constructs, and microfluidic systems.
• Evaluation of models' ability to reproduce fibrosis-related characteristics and their biological relevance.

Main Results:

• 3D in vitro liver models surpass 2D cultures in recapitulating key fibrotic features like ECM remodeling and hepatic stellate cell activation.
• Models demonstrate physiological relevance by reproducing collagen deposition in a 3D setting.
• Liver organoids and assembloids offer architectural complexity and scalability for mechanistic insights and therapeutic evaluation.

Conclusions:

• 3D in vitro models bridge the gap between in vitro and in vivo studies by replicating liver architecture and microenvironments.
• Standardized protocols can enhance reproducibility, advancing drug discovery for liver fibrosis.
• These models show significant potential for developing personalized therapies for liver fibrosis.