Multi-organ model with microchannel-linked organoids for NAFLD drug screening
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Solution Overview
Problem
Current models for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) lack effective therapeutic methods and animal models, and existing in vitro models fail to accurately mimic the complex organ interactions involved in metabolic diseases like obesity, diabetes, and hypertension.
Innovation Solution
A multi-organ model comprising liver, intestinal, pancreas, and cardiac organoids connected by microchannels, treated with free fatty acids to mimic NAFLD, allowing for drug screening and toxicity evaluation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional test methods are used with separate cell cultures for each organ, then each organ can be cultured under its specific conditions, but the complex interactions between various organs cannot be reflected
Solution Approach 1:
The model segments different organs into separate organoid cultures (liver, intestine, adipose tissue, immune system) while connecting them through a shared culture medium system. This allows each organ to be cultured under its specific conditions while still enabling inter-organ interactions through the medium, resolving the contradiction between maintaining organ-specific culture conditions and reflecting complex organ interactions.
Solution Approach 2:
The culture medium serves multiple functions: it provides nutrients for individual organoids, facilitates communication between organs, and enables the study of systemic metabolic interactions. This multi-functional medium system allows the model to reflect complex organ interactions without requiring separate specialized systems for each function.
2Reliability
If animal models are used for NAFLD research, then disease pathology can be studied, but animal ethics issues arise and suitable models are not well-established
Solution Approach 1:
The invention creates an in vitro copy of the human metabolic system using human-derived organoids that replicate the physiological functions and interactions of liver, intestine, adipose tissue, and immune system. This human-based model system provides reliable NAFLD pathology research without requiring animal subjects, thus eliminating animal ethics issues while maintaining disease model accuracy.
3Adaptability or versatility
If a multi-organ model is created to reflect organ interactions, then drug metabolism and toxicity can be evaluated, but the device complexity increases significantly
Solution Approach 1:
The model merges multiple organoid cultures into a single integrated system where all organs share a common culture medium environment. This allows drug metabolism and toxicity to be evaluated across multiple organs simultaneously without requiring separate complex evaluation systems for each organ, thus providing comprehensive drug evaluation capability while managing device complexity through integration.
Data Source
AI summary
The present disclosure relates to a multi-organ model, and the multi-organ model of the present disclosure is excellent in culturing each organoid due to linkage between organoids and properties of hydrogel and can more accurately reflect the interactions between organs and the microenvironment in vivo. Also, the multi-organ model is further subjected to free fatty acid treatment and thus can more accurately mimic the phenotypes of non-alcoholic fatty liver. Accordingly, it is possible to analyze the effects of candidate drugs on peripheral organs.