Alternatives to animal research: from in vitro to ex vivo liver models

Abstract

Understanding the critical importance of reducing reliance on traditional research animal models in liver disease research, this thesis focused on advancing the development of more sophisticated, physiologically relevant, and ethically aligned models. These alternatives aimed to effectively simulate the complexities of liver disease, fostering the exploration of novel therapeutic strategies and a more comprehensive understanding of liver pathophysiology without compromising ethical standards. In chapter 3, the study offered critical insights into the use of nanofibrillar cellulose as an effective scaffold material for tissue engineering, providing a viable alternative to animal-based models. By shedding light on the interplay between cellulase enzyme concentration, flow conditions, and fibroblast spheroid cultures within nanocellulose hydrogels, the research enhanced our understanding of the cell microenvironment and contributed to the advancement of ethical and effective alternatives to animal-based disease modeling. Furthermore, chapter 4 addressed the pressing need for reliable and clinically applicable liver disease models. Through a systematic assessment of cellulose nanofibril hydrogels as a viable alternative to traditional Matrigel, the research presented a pathway for the development of more standardized and ethically sound liver disease models, fostering a more responsible approach to liver disease research and therapeutic development. Chapter 5 represented a crucial step forward in the quest for advanced large-animal models that closely mimicked human liver physiology. By successfully generating and integrating porcine intrahepatic cholangiocyte organoids into porcine liver scaffolds, the research provided a promising animal-free platform for studying complex liver pathologies and advancing therapeutic interventions, ultimately reducing the reliance on traditional research animal models. Lastly, chapter 6 introduced a practical and ethical alternative to animal-based studies, emphasizing the importance of developing comprehensive research alternatives. By accurately replicating biochemical markers of liver damage, the platform served as a promising solution for studying metabolic and toxic liver disorders without the need for traditional research animal models, contributing to the establishment of a more ethical and effective paradigm in liver disease research. In conclusion, these endeavors mark significant progress in the field of liver tissue engineering and disease modeling, emphasizing the importance of advancing sophisticated and ethically aligned research alternatives. Through the development of these innovative models, the research not only furthers our understanding of liver disease mechanisms but also significantly contributes to the ongoing effort to reduce the dependence on traditional research animal models in liver disease research.