The Material World of 3D-Bioprinted and Microfluidic-Chip Models of Human Liver Fibrosis

Biomaterials are extensively used to mimic cell-matrix interactions, which are essential for cell growth, function, and differentiation. This is particularly relevant when developing in vitro disease models of organs rich in extracellular matrix, like the liver. Liver disease involves a chronic wound-healing response with formation of scar tissue known as fibrosis. At early stages, liver disease can be reverted, but as disease progresses, reversion is no longer possible, and there is no cure. Research for new therapies is hampered by the lack of adequate models that replicate the mechanical properties and biochemical stimuli present in the fibrotic liver. Fibrosis is associated with changes in the composition of the extracellular matrix that directly influence cell behavior. Biomaterials could play an essential role in better emulating the disease microenvironment. In this paper, the recent and cutting-edge biomaterials used for creating in vitro models of human liver fibrosis are revised, in combination with cells, bioprinting, and/or microfluidics. These technologies have been instrumental to replicate the intricate structure of the unhealthy tissue and promote medium perfusion that improves cell growth and function, respectively. A comprehensive analysis of the impact of material hints and cell-material interactions in a tridimensional context is provided.