Encapsulated Liver Tissue for Function Restoration
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Solution Overview
Problem
Current treatments for liver failure and metabolic liver diseases are limited by organ shortages, immunosuppression requirements, and the need for lifelong medication, while existing toxicity testing methods are costly and raise animal welfare concerns, and there is a lack of effective in vitro models for liver metabolism and toxicity assessment.
Innovation Solution
Development of encapsulated liver tissue comprising hepatic, mesenchymal, and endothelial cells within a biocompatible cross-linked polymer, which can be used to restore liver functions and determine hepatic metabolism and hepatotoxicity of agents, and can be produced through a process involving the culture and encapsulation of liver organoids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If liver transplantation is performed to treat liver failure, then liver functions are restored, but organ shortage limits availability and lifelong immunosuppression is required
Solution Approach 1:
The invention segments the liver into functional units by using primary liver cells that can be cultured and expanded independently. These cells can be transplanted as discrete cellular preparations rather than requiring whole organ transplantation, thereby increasing the effective quantity of functional liver tissue available for treatment.
Solution Approach 2:
The invention introduces an intermediary cellular preparation between organ donation and patient treatment. Cultured primary liver cells serve as an intermediate product that can be produced in controlled conditions and transplanted without requiring immunosuppression, thus resolving the contradiction between restoring liver function and avoiding lifelong medication.
2Reliability
If liver transplantation is performed to treat liver failure, then liver functions are restored, but lifelong immunosuppression is required
Solution Approach 1:
The invention extracts the essential functional component (primary liver cells) from the complex organ system and transplants only these cells. This cellular preparation can be administered without the need for whole organ transplantation and the associated immunosuppression protocols, thereby simplifying the treatment regimen while maintaining liver function restoration.
Solution Approach 2:
The invention uses cultured primary liver cells that can be produced in controlled conditions and transplanted as a temporary or permanent functional replacement. These cellular preparations can be generated on-demand without requiring complex immunosuppression protocols, effectively replacing the need for lifelong medication while restoring liver functions.
3Object-affected harmful factors
If in vitro model systems are used for toxicity testing, then animal welfare is improved and cost is reduced, but predictive accuracy for human adverse effects is disputed
Solution Approach 1:
The invention changes the fundamental parameter of the testing system from using animal models to using human primary liver cells cultured in vitro. This parameter change maintains or improves predictive accuracy for human adverse effects while simultaneously improving animal welfare and reducing costs, as the testing is performed on human cells that more accurately reflect human metabolic responses.
Solution Approach 2:
The invention creates an in vitro copy of human liver tissue using primary human hepatocytes and other liver cell types. This cellular model system replicates human liver metabolism and toxicity responses more accurately than animal models, thereby improving predictive accuracy while eliminating the need for animal testing.
4Reliability
If primary liver cells are transplanted to treat liver disease, then transient improvement is achieved, but cell quality variability and repeated injections are required
Solution Approach 1:
The invention performs preliminary culture and expansion of primary liver cells before transplantation. This preliminary action allows for quality control and standardization of the cellular preparation, reducing variability in cell quality. The cells are prepared in advance under controlled conditions, ensuring consistent therapeutic effect and potentially reducing the need for repeated injections.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The encapsulated liver tissue provides a viable and biologically active solution for temporary liver function replacement, reducing the need for transplantation and immunosuppression, and offers an efficient and humane method for evaluating chemical toxicity and metabolism.
Implementation Method 1
encapsulated within a biocompatible cross-linked polymer
Implementation Method 2
at least one liver organoid is substantially covered with the first biocompatible cross-linked polymer
Implementation Method 3
determining the hepatic metabolism and/or hepatotoxicity of an agent
Implementation Method 4
the loss of the liver's synthetic and detoxifying functions
Implementation Method 5
restoring or improving liver functions
Implementation Method 6
hepatic metabolism of an agent
Data Source
AI summary
The present disclosure provides an encapsulated liver tissue that can be used in vivo to improve liver functions, in vitro to determine the hepatic metabolism and/or hepatotoxicity of an agent and ex vivo to remove toxic compounds from patients’ biological fluid. The encapsulated liver tissue comprises at least one liver organoid at least partially covered with a biocompatible cross-linked polymer. Processes for making the encapsulated liver tissue are also provided.