Human Pancreas Scaffolds Decellularization
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Solution Overview
Problem
Current methods for developing 3D human liver tissue scaffolds face challenges due to the unique macroscopic and microscopic anatomy of the human liver, which differs significantly from other mammals, making it difficult to replicate the complexity of human liver disease in vitro models, and existing decellularization techniques have not successfully produced human liver scaffolds.
Innovation Solution
A method involving mechanical damage, osmotic stress, protease/DNAase treatment, and detergent exposure, combined with flow shear stress, is used to decellularize human pancreas tissue, producing a scaffold that retains the 3D architecture and bioactivity of the extracellular matrix, which can be adapted for liver tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If decellularisation techniques are applied to human liver tissue, then cellular material is removed, but the unique human liver architecture is damaged or lost
Solution Approach 1:
The patent applies parameter changes by systematically varying physical parameters (flow rate, pressure, temperature) and chemical parameters (detergent concentration, enzyme concentration, exposure time) to optimize the decellularisation process. This allows effective cell removal while preserving the delicate human liver architecture, resolving the contradiction between decellularisation efficiency and architectural preservation
Solution Approach 2:
The patent employs periodic action through cyclic perfusion protocols where the liver tissue is alternately exposed to decellularisation solutions and washing buffers. This periodic application of mechanical and chemical forces gradually removes cellular material while allowing the ECM structure to recover and maintain its integrity, thereby preserving human liver architecture during decellularisation
2Productivity
If animal liver scaffolds are used for human cell repopulation, then scaffold availability is improved, but species-specific architectural differences cause functional incompatibility
Solution Approach 1:
The patent applies the copying principle by creating an accurate replica of human liver architecture through decellularisation of human liver tissue itself. This produces a human-derived ECM scaffold that perfectly copies the native human liver structure, ensuring architectural compatibility with human cells while maintaining scaffold availability for transplantation applications
3Reliability
If multiple decellularisation cycles are performed, then cellular material is more completely removed, but the ECM structure becomes damaged
Solution Approach 1:
The patent applies partial action by using optimized, controlled exposure times to decellularisation agents that are sufficient to achieve complete cell removal but not excessive enough to damage the ECM. The protocol carefully balances the degree of action to achieve the minimum necessary decellularisation effect while preserving ECM structural integrity
Solution Approach 2:
The patent employs beforehand cushioning by pre-treating the tissue with protective agents and using gradual, stepwise increases in detergent and enzyme concentrations. This cushioning approach prevents sudden structural damage while ensuring complete decellularisation, allowing multiple cycles to be performed safely without compromising ECM integrity
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
This method effectively produces acellular human pancreas scaffolds that maintain the three-dimensional architecture and bioactivity of the ECM, enabling the reproduction of the human liver microenvironment for disease modeling and potential use in transplantation.
Implementation Method 1
subjecting the cells in the tissue to osmotic stress by exposing the tissue to a hypotonic reagent or hypertonic reagent
Implementation Method 2
the human pancreas tissue is subjected to flow shear stress generated by perfusing the human pancreatic tissue in a retrograde direction during step (ii) to (v)
Data Source
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AI summary
This invention relates to methods for decellularising human liver tissue to produce human hepatic extracellular matrix (ECM) scaffolds, for example for use in therapy or disease modelling. The methods involve mechanically damaging cells in the tissue, for example by freeze thaw, and then subjecting the liver tissue to multiple cycles of osmotic stress, detergent treatment and protease and/or DNAase treatment to produce a decellularised human ECM scaffold.