Large Animal Biliary Atresia Model via Duct Sclerosis

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Solution Overview

Problem

Current biliary atresia models, particularly those using bile duct ligation, fail to accurately recapitulate human biliary atresia, lacking in both accuracy and reproducibility in mimicking the disease progression.

Innovation Solution

A large animal model simulating human biliary atresia is developed by administering an agent causing sclerosis of intrahepatic bile ducts, which closely replicates the human condition, allowing for the performance of complex surgical procedures like the Kasai procedure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If bile duct ligation is used to create a biliary atresia model, then the model can be established, but it fails to accurately recapitulate human biliary atresia and lacks reproducibility

Engineering Contradiction:

Improveaccuracy of disease modelVSAvoidreproducibility of disease model

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the methodological parameters from simple bile duct ligation to a multi-step protocol involving partial bile duct ligation followed by administration of toxic agents (such as carbon tetrachloride or ethinylestradiol). This parameter transformation creates more consistent and reproducible bile duct injury that accurately mimics human biliary atresia pathophysiology, resolving the contradiction between model accuracy and reproducibility.

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If small animal models are used, then the model is easier to handle, but there is not enough room to perform the Kasai procedure

Engineering Contradiction:

Improveease of animal handlingVSAvoidability to perform Kasai procedure

Core Design Contradiction:

Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent introduces a size intermediary by using medium-sized animals (such as pigs or sheep) that serve as a bridge between small laboratory animals and human patients. These intermediary models are large enough to accommodate the Kasai procedure and provide adequate surgical access, while still being manageable in a research setting, thus resolving the contradiction between ease of handling and surgical adaptability.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If current biliary atresia models are used, then the model can be established, but the hepatic fibrosis is unlike human disease

Engineering Contradiction:

Improveaccuracy of disease progressionVSAvoidsimplicity of model establishment

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by first establishing partial bile duct ligation to create initial cholestasis, then subsequently administering toxic agents to induce progressive liver injury and fibrosis. This staged approach allows the liver to undergo a more natural progression of injury and repair cycles, resulting in human-like fibrotic patterns rather than the simple scarring seen in direct ligation models, thereby improving disease accuracy while maintaining reasonable model establishment simplicity.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20250169479A1Biliary atresia model

Publication Date: 2025.05.29 SAINT LOUIS UNIV

AI summary

The present disclosure relates to animal models simulating human biliary atresia. The model includes a large animal treated with an agent causing sclerosis of intrahepatic bile ducts in the animal to simulate human bile duct injury.