Dissertation

Microphysiological liver systems for in vitro modeling and industry implementation

This thesis tackles the difficulty of predicting the liver’s clinical response to novel therapies, a challenge arising from interspecies differences and limitations of existing in vitro models.

Author: F.F. Bonanini
Date: 03 April 2025
Links: Thesis in Leiden Repository

It focuses on developing advanced liver microphysiological systems (MPS) to create complex, physiologically relevant platforms that incorporate fluid flow, 3D cellular arrangements, and diverse cell populations, mimicking the liver’s microenvironment. The goal is to enhance predictability while ensuring ease of use, reproducibility, and throughput for pharmaceutical adoption. The study emphasizes key considerations: the relevance of cell sources, microfluidic platforms, physiological microenvironments, and suitable readouts. Firstly, it compares the metabolic competence of various hepatocyte models under a metabolic challenge. The research then introduces a vascularized MPS using a standardized microfluidic system, achieving reproducible vascularization of 3D liver constructs. It further develops a fibrin-based, self-assembled microvascular network with liver-derived cells, enabling assays for steatosis and fibrosis. Finally, a method for retrieving cells from these systems is established for detailed molecular analysis.