Acellularized Heart Tissue Graft via Sequential Detergent and Osmotic Processing
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Solution Overview
Problem
Current methods for acellularizing heart tissue for transplantation often result in calcifications and other disadvantages, such as immune rejection and hyperplasia, due to the removal of immunogenic components and the use of chemical agents that can be toxic and affect the mechanical and geometric properties of the tissue.
Innovation Solution
A method involving the use of an aqueous solution with sodium deoxycholate and sodium dodecyl sulfate to remove cells from heart tissue, followed by osmotic treatment with distilled water and washing with physiological saline solution, which helps maintain the integrity of the extracellular matrix and ensures a stable, functionally intact acellularized heart tissue matrix.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical agents are used to remove cells from heart tissue, then cell removal effectiveness is improved, but tissue mechanical properties and geometric integrity deteriorate
Solution Approach 1:
The acellularization process is divided into multiple sequential steps with different solutions: first an anionic detergent solution for initial cell removal, then a non-ionic detergent solution for further cleaning, followed by osmotic treatment with distilled water, and finally physiological saline washing. This segmentation allows each step to target specific cellular components while progressively preserving tissue integrity.
Solution Approach 2:
The patent specifies precise concentration parameters for each chemical solution used in the process. The anionic detergent solution contains 0.1-5% sodium deoxycholate and 0.1-5% SDS, while the non-ionic detergent solution contains 0.1-5% Triton X-100. These controlled parameter changes ensure effective cell removal while minimizing damage to the extracellular matrix mechanical properties.
2Reliability
If strong anionic detergents are used for acellularization, then cell lysis effectiveness is improved, but tissue toxicity and calcification risk increase
Solution Approach 1:
The patent introduces an intermediary non-ionic detergent solution (Triton X-100) that acts as a bridge between the strong anionic detergent treatment and the final tissue product. This intermediary step completes the cell removal process while being less toxic to the tissue, reducing calcification risk and preserving matrix integrity.
Solution Approach 2:
The patent converts the potentially harmful effect of strong anionic detergents by immediately following their use with osmotic treatment using distilled water. This osmotic step reverses any damaging concentration effects and swelling, transforming the harmful high-concentration detergent exposure into a beneficial controlled process that preserves tissue viability.
3Object-affected harmful factors
If cells are completely removed from heart tissue, then immune rejection is eliminated, but tissue structural integrity and functionality deteriorate
Solution Approach 1:
The patent applies different treatment intensities to different regions and depths of the tissue. The acellularization process is designed to penetrate and remove cells from the luminal surface and through the tissue thickness, while the extracellular matrix framework is preserved throughout. This local differentiation ensures complete immunogenic component removal while maintaining overall structural integrity.
Solution Approach 2:
The patent performs preliminary stabilization of the extracellular matrix before final tissue processing. By establishing a robust matrix framework early in the process through controlled chemical treatment and osmotic balancing, the tissue is prepared to withstand complete cell removal without collapsing or losing its functional geometry.
4Reliability
If mechanical treatment is used to remove cells, then cell detachment is improved, but extracellular matrix damage increases
Solution Approach 1:
The patent completely replaces mechanical cell removal methods with chemical and osmotic approaches. Instead of using enzymes, abrasion, or mechanical disruption, the process uses anionic and non-ionic detergents to lyse and detach cells chemically, followed by osmotic treatment with distilled water to complete cell removal. This substitution eliminates mechanical stress on the extracellular matrix while achieving complete cell detachment.
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 produces acellularized heart tissue transplants with good mechanical and physiological properties, suitable for transplantation with or without repopulation, and has a long shelf life, maintaining the natural morphology and basement membrane integrity.
Implementation Method 1
removing cells located in the tissue from the extracellular matrix with the aid of an acellularization solution from an aqueous solution of at least one strong anionic detergent containing at least sodium deoxycholate
Implementation Method 2
Chemical agents used to detach, digest or lyse the cells include alkaline solutions, enzymes, glycerin, non-ionic and ionic detergents
Implementation Method 3
osmotically treating the tissue with distilled or deionized water
Implementation Method 4
Treating the tissue with physiological saline solution
Data Source
Figure 1a~1d
Figure 2
AI summary
The invention relates to a method for producing a bioartificial heart tissue graft, which leads to excellent biomechanical properties on the product and guarantees a high cell freedom with optimal preservation of the matrix. During the method, biological cells of a heart tissue preparation, particularly a heart valve or a heart vessel adhering in and/or to an extracellular matrix, are removed in-vitro. The method comprises that following steps carried out in this sequence: a) providing the heart tissue preparation of natural origin; b) removing cells, which are located in the tissue, from the extracellular matrix with the aid of an acellularization solution consisting of an aqueous solution of at least one strong anionic detergent and at least containing sodium deoxycholate; c) osmotically treating the tissue with distilled or deionized water, and; d) treating the tissue with a physiological saline solution with continuous flow or exchanging of the rinsing solution three times.