Corneal Tissue Decellularization via Mild Detergents and Polyalcohols
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Solution Overview
Problem
Current methods for decellularizing corneal tissue to prevent immune responses and maintain transparency are inadequate, as they often alter the tissue structure and lead to clouding, which compromises vision.
Innovation Solution
A method involving the use of gentle detergents like lipopeptides, specifically cyclic lipoheptapeptides, in combination with polyalcohols such as glycerol, and additional decellularizing agents like deoxycholic acid, along with enzymes like α-galactosidase and DNase, to remove cellular components while preserving the extracellular matrix and maintaining tissue transparency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If strong decellularizing agents like SDS are used, then cell components are removed effectively, but the extracellular matrix structure is significantly altered causing tissue clouding
Solution Approach 1:
The patent changes the chemical parameters of the decellularization process by using mild detergents (0.1-1% v/v) combined with polyalcohols (10-50% v/v) at controlled temperatures (4-37°C) over extended periods (24-72 hours). This parameter optimization achieves effective decellularization while preserving the native collagen fibril structure and tissue transparency, avoiding the structural damage caused by strong agents like SDS.
Solution Approach 2:
The patent employs a composite decellularization system combining mild detergents (such as Triton X-100, Tween 20, or Brij 35) with polyalcohols (such as glycerol, polyethylene glycol, or polypropylene glycol). This composite approach synergistically enhances cell removal effectiveness while the polyalcohol component protects the extracellular matrix structure, preventing clouding and maintaining tissue integrity.
2Object-affected harmful factors
If decellularization is performed to prevent immune responses, then immunogenicity is reduced, but tissue transparency is compromised due to structural alterations
Solution Approach 1:
The patent optimizes decellularization parameters including using low concentrations of mild detergents (0.1-1% v/v), controlling temperature (4-37°C), and extending treatment time (24-72 hours). These parameter adjustments ensure complete removal of immunogenic cell components while preserving the regular collagen fibril arrangement necessary for light transmission, thus maintaining tissue transparency.
Solution Approach 2:
The patent uses a composite solution of mild detergents and polyalcohols where the detergent removes cell membranes and nuclear material to reduce immunogenicity, while the polyalcohol component acts as a structure-preserving agent that maintains collagen fibril organization and prevents tissue clouding, thereby preserving optical transparency.
3Reliability
If extensive decellularization is performed to remove all cell components, then immune compatibility is improved, but the chemical intervention significantly alters the tissue
Solution Approach 1:
The patent carefully controls chemical intervention parameters by using low concentrations of mild detergents (0.1-1% v/v), maintaining physiological temperatures (4-37°C), and optimizing treatment duration (24-72 hours). These controlled parameters enable thorough removal of immunogenic components while minimizing chemical damage to the extracellular matrix, preserving native tissue composition and biochemical properties.
Solution Approach 2:
The patent employs a composite decellularization solution where mild detergents selectively remove cell membranes, proteins, and nuclear material for immune compatibility, while polyalcohols (10-50% v/v) act as protective agents that stabilize the extracellular matrix structure. This composite approach achieves complete decellularization with minimal alteration to tissue composition and native biochemical characteristics.
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 corneal tissue without altering its structure, ensuring transparency and minimizing immune responses, as demonstrated by the preservation of shrinkage temperature and significant reduction of α-Gal epitopes, resulting in transparent and immunologically compatible corneal tissue for transplantation.
Implementation Method 1
Without being bound to this theory, the inventors assume that introducing the polyalcohol, preferably in the above-mentioned concentration, results in osmotic pressure as a result of the difference in the concentration of the polyalcohol in the tissue and in the surrounding solution, causing the polyalcohol to be introduced into the corneal tissue, releasing water.
Implementation Method 2
Detergents that are gentle on the tissue shall be understood herein to mean decellularizing agents that fulfill the task of removing cell membranes, intracellular proteins, cell nuclei and other cell components as completely as possible from the tissue
Data Source
AI summary
The present invention relates to a method for preparing corneal tissue for applications predominantly in transplantation, and to the use of a solution for decellularizing corneal tissue. The present invention further relates to transparent corneal tissue.