Acellular Cornea via Supercritical Fluid Decellularization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing acellular corneas for transplantation often result in structural mismatch and immune rejection due to residual cellular materials and chemicals, which can lead to neovascularization and other complications.
Innovation Solution
An ex-vivo method involving supercritical fluid treatment of corneas without the use of proteases, chelating agents, detergents, or glycerol, where the cornea is immersed in a salt solution and treated with supercritical carbon dioxide or nitrous oxide in the presence of ethanol, preserving the native structure and reducing immunogenic residues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional decellularization methods using proteases, chelating agents, detergents, or glycerol are used, then cells are removed from the cornea, but residual cellular materials and chemicals remain causing immune response and structural damage
Solution Approach 1:
The patent changes the physical state parameters of the treatment medium by using supercritical carbon dioxide (temperature above 31.1°C and pressure above 73.8 bar) instead of conventional liquid chemicals. This parameter change allows effective decellularization while avoiding residual harmful substances, as supercritical CO2 can be completely evaporated leaving no trace
Solution Approach 2:
The patent replaces chemical decellularization mechanisms (proteases, chelating agents, detergents) with a physical mechanism using supercritical fluid extraction. The supercritical CO2 penetrates the corneal tissue and extracts cellular materials through solvation and diffusion, eliminating the need for harmful chemicals while maintaining structural integrity
2Manufacturing precision
If supercritical fluid treatment is applied, then decellularization is achieved with preserved structure, but the process requires high pressure and temperature conditions
Solution Approach 1:
The patent utilizes the unique properties of supercritical carbon dioxide by adjusting temperature and pressure parameters to achieve the supercritical state. This allows the CO2 to penetrate deep into the corneal tissue effectively, providing thorough decellularization while the subsequent complete evaporation ensures no residual pressure or chemical damage remains
3Adaptability or versatility
If porcine corneas are used for transplantation, then refractive index and size match human corneas, but severe immune response and transplant rejection occur
Solution Approach 1:
The patent applies supercritical fluid extraction to remove all immunogenic cellular materials from porcine corneas, including cell membranes, proteins, and other antigens. This extraction process preserves the extracellular matrix structure and the cornea's optical properties while eliminating the components that trigger immune rejection, making xeno-transplantation feasible
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 decellularizes corneas, maintaining their integrity and collagen structure, reducing immune response, and providing a scaffold for host cell growth, thus enhancing the success of corneal transplantation by minimizing rejection and promoting tissue repair.
Implementation Method 1
the tissue (such as a pig aorta) is subjected to a mixture of supercritical carbon dioxide and ethanol under a pressure of 15 or 30 MPa, at a temperature of 37 °C for 30 or 60 minutes for significantly removing the amounts of residual phospholipids
Data Source
Figure 1
Figure 2A
Figure 2B
AI summary
A method of producing an acellular cornea includes steps of subjecting a cornea of an animal to a de-cellularization process, and has not the step of treating the cornea with a protease, a chelating agent, a detergent, a glycerol, or a combination thereof. When a native cornea is processed by the method, the native structure and conformation of the native cornea are preserved while immunogenic matters are reduced to a level that the thus produced cornea may serve as a three-dimensional scaffold for host cells to grow thereon after transplantation.