Decellularized Tissue Hydrogel via Supercritical Fluid Extraction
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Solution Overview
Problem
Existing decellularization methods using surfactants denature proteins, destroy tissue microstructure, and remove cytokines and growth factors, while high-pressure systems like hydrostatic pressure can cause structural deformation due to ice crystal formation.
Innovation Solution
A supercritical fluid-organic solvent system is used to decellularize tissues, preserving proteins and growth factors by disrupting cell membranes without chemicals, followed by washing, pH titration, and mixing with gels to enhance angiogenesis and tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If surfactants or enzymes are used to decellularize tissues, then cell debris is removed effectively, but proteins are denatured, tissue microstructure is destroyed, and cytokines and growth factors are removed
Solution Approach 1:
The patent changes the physical state and parameters of the decellularization medium by using supercritical carbon dioxide (high pressure and temperature conditions) instead of conventional surfactants or enzymes. This parameter change allows effective cell membrane disruption while preserving proteins and tissue structure, as the supercritical fluid can penetrate tissues without causing denaturation or structural damage.
Solution Approach 2:
The patent replaces the chemical decellularization mechanism (surfactants/enzymes) with a physical mechanism (supercritical fluid extraction). The supercritical carbon dioxide uses its unique solvation properties under high pressure to disrupt cell membranes through physical dissolution of lipids, rather than through chemical denaturation, thereby preserving protein integrity and tissue microstructure.
2Quantity of substance
If hydrostatic pressure system is used to decellularize tissues, then cell disruption is achieved, but ice crystals form in tissues causing structural deformation of extracellular matrix
Solution Approach 1:
The patent utilizes the phase transition properties of carbon dioxide between supercritical and gaseous states. By maintaining CO2 in a supercritical state during decellularization and then allowing it to return to gaseous state for removal, the process achieves cell disruption without water present to form ice crystals, thereby preserving extracellular matrix structure.
Solution Approach 2:
The patent replaces the hydrostatic pressure mechanism that causes ice crystal formation with supercritical fluid extraction. The supercritical carbon dioxide achieves cell disruption through solvation and diffusion mechanisms rather than mechanical pressure alone, avoiding the formation of ice crystals that deform tissue structure.
3Reliability
If supercritical fluid-organic solvent system is used to decellularize tissues, then cell membranes are disrupted without chemicals, but process complexity increases
Solution Approach 1:
The patent employs supercritical carbon dioxide, which has the unique property of being easily removable by simply releasing pressure and returning to gaseous state. This self-service characteristic simplifies the overall process despite the initial complexity of achieving supercritical conditions, as no additional chemical removal steps are needed and the system automatically purifies the decellularized tissue.
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 method effectively preserves tissue-derived proteins and growth factors, improving angiogenesis and tissue regeneration capabilities of the decellularized hydrogel, with improved physical properties and reduced degradation by body fluids.
Implementation Method 1
a step of decellularizing a biological tissue by bringing the same to contact with a supercritical fluid and an organic solvent at the same time
Implementation Method 2
a step of titrating the decellularized tissue solution to pH 5.5-7.8 by treating with a basic solution
Implementation Method 3
a step of allowing the titrated decellularized tissue solution to stand at 30-40° C.
Data Source
AI summary
A method for preparing a decellularized tissue-based hydrogel with maximized ability of preserving various tissue-derived proteins, growth factors and cytokines by using a supercritical fluid-organic solvent system through (a) a step of decellularizing a biological tissue by bringing the same to contact with a supercritical fluid and an organic solvent at the same time; (b) a step of washing the decellularized tissue; (c) a step of preparing a decellularized tissue solution by mixing the washed decellularized tissue with one selected from an enzyme solution, an acidic solution and a mixture thereof; (d) a step of titrating the decellularized tissue solution to pH 5.5-7.8 by treating with a basic solution; and (e) a step of allowing the titrated decellularized tissue solution to stand at 30-40° C. and utilizing the same as a tissue engineering material with improved angiogenesis and tissue regeneration abilities.