Modular Bio-artificial Liver Chamber for Hepatocyte Proliferation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current liver support technologies, including both artificial and bio-artificial liver machines, are inadequate in replacing the complex functions of the liver, particularly in acute and chronic liver disease and failure, due to limitations in detoxification, biotransformation, and synthesis, and face challenges in scaling up for human use while maintaining functional liver capacity.
Innovation Solution
A modular bio-artificial liver chamber that allows for the proliferation, cryopreservation, and perfusion of human hepatocyte cell lines encapsulated in alginate beads within a fluidised bed reactor, providing a 3-D environment for cell growth and function, and includes a scalable method for manufacturing and deploying the biological component for extracorporeal use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hollow fibre cartridges with membranes are used to separate cells from plasma, then cell containment is achieved, but mass transfer limitations occur
Solution Approach 1:
The invention removes the membrane component entirely from the system. Instead of using hollow fibre cartridges with membranes that create mass transfer barriers, the patent employs a membrane-free bioreactor where cells are contained within a perfusable matrix that allows direct plasma-cell interaction, eliminating the mass transfer limitations imposed by membranes while maintaining cell containment.
Solution Approach 2:
The invention introduces a perfusable matrix as an intermediary structure that replaces the membrane function. This matrix provides structural support and cell containment while simultaneously allowing efficient mass transfer of nutrients, waste products, and therapeutic molecules between plasma and cells, solving the contradiction between containment and transfer efficiency.
2Quantity of substance
If animal hepatocytes are used in bio-artificial livers, then mass transfer limitations are reduced, but human-specific liver functions are not fully replicated
Solution Approach 1:
The invention changes the biological parameter by using human-derived hepatocyte cell lines instead of animal hepatocytes. This substitution maintains the mass transfer efficiency achieved with animal cells while introducing human-specific metabolic pathways and functions, thereby replicating human liver functions more accurately including drug metabolism and detoxification pathways specific to humans.
3Adaptability or versatility
If primary hepatocytes are used, then human liver function is better replicated, but cell proliferation and long-term functionality are limited
Solution Approach 1:
The invention applies preliminary action by pre-differentiating and pre-characterizing human hepatocyte cell lines before implantation. The cells are selected and prepared to ensure they possess both human-specific functional characteristics and enhanced proliferative capacity, allowing them to maintain long-term functionality in the bioreactor while replicating human liver functions.
Solution Approach 2:
The invention changes the cellular state parameter by using immortalized or specially cultured hepatocyte cell lines that have been modified to overcome the limited lifespan of primary hepatocytes. These cell lines maintain human liver function characteristics while acquiring extended replicative capacity through cultural conditioning or genetic modification.
4Productivity
If large-scale bioreactors are designed for human use, then treatment capacity is increased, but maintaining functional liver capacity becomes more difficult
Solution Approach 1:
The invention applies segmentation by designing modular bioreactor units that can be scaled by adding parallel modules rather than increasing the size of a single reactor. Each module maintains optimal cell-to-plasma contact characteristics and functional density, allowing the overall treatment capacity to increase while each individual module preserves reliable human liver function replication.
Solution Approach 2:
The invention transitions from scaling in one dimension (increasing reactor volume) to scaling in another dimension (increasing number of parallel modules). This dimensional change allows treatment capacity to scale linearly with the number of modules while each module maintains the optimized cell density and plasma flow characteristics necessary for reliable human liver function.
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 system achieves functional liver capacity on a per-cell basis, mimicking in vivo liver functions such as clotting factor synthesis and steroid metabolism, and has demonstrated improved clinical and biochemical parameters in animal models and human plasma, with the potential for scalable and safe deployment in clinical settings.
Implementation Method 1
human hepatocyte cell lines encapsulated in alginate beads within a fluidised bed reactor
Implementation Method 2
human hepatocyte cell lines encapsulated in alginate beads
Data Source
Figure 1
Figure 2A~2B
Figure 3a~3b
AI summary
The present invention relates to the field of extracorporeal liver perfusion and, more particularly, to a method of proliferating human hepatocyte derived cells. It comprises; a) Seeding cells into a matrix forming agent; b) Pre-culturing the matrix encapsulated cells so that they form cohesive spheroids and; c) Growing them to performance competence.