Bioprosthetic Tissue Crosslinking With Inert Atmosphere
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Solution Overview
Problem
Current tissue processing methods for bioprosthetic devices face challenges such as enzymatic degradation, antigenicity, and calcification, which affect the performance and structural integrity of medical devices, particularly bioprosthetic heart valves, due to the use of potent chemicals and self-polymerization of glutaraldehyde during crosslinking.
Innovation Solution
The method involves crosslinking tissue with a dialdehyde crosslinking agent, specifically glutaraldehyde, under a low oxygen atmosphere in a substantially unpolymerized state, and using contoured forms for precise shaping and stabilization, combined with treatments to reduce calcification and cytotoxicity, including the use of porous forms and 3D printing for custom prostheses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If tissue is crosslinked using conventional methods with glutaraldehyde, then tissue stability is improved, but glutaraldehyde self-polymerization occurs causing reduced flexibility and increased brittleness
Solution Approach 1:
The patent applies an inert atmosphere (nitrogen or carbon dioxide) during the crosslinking process to prevent glutaraldehyde self-polymerization. By replacing oxygen with inert gas, the harmful oxidation reactions are eliminated while maintaining the beneficial crosslinking effects, thus preserving tissue flexibility while achieving stability.
Solution Approach 2:
The patent modifies the chemical environment parameters by controlling pH levels and using buffer solutions during crosslinking. This parameter control prevents unwanted polymerization reactions while maintaining effective crosslinking, resolving the contradiction between stability and flexibility.
2Stability of the object's composition
If potent chemicals are used for tissue treatment, then fixation and stabilization are improved, but tissue degradation and cytotoxicity increase
Solution Approach 1:
The inert atmosphere prevents oxidative degradation of tissue while maintaining effective fixation. By eliminating oxygen, the patent prevents harmful oxidation reactions that would otherwise degrade tissue structure and increase cytotoxicity, thus achieving stable fixation without tissue damage.
Solution Approach 2:
The patent introduces buffer solutions and pH control mechanisms as intermediaries to moderate the chemical treatment process. These intermediaries allow effective fixation to occur while preventing excessive chemical reactivity that would cause tissue degradation and cytotoxicity.
3Duration of action of stationary object
If tissue is crosslinked to reduce calcification, then long-term structural integrity is improved, but antigenicity and immunogenicity may increase
Solution Approach 1:
By conducting crosslinking in an inert atmosphere, the patent achieves thorough stabilization that prevents calcification without requiring excessive chemical treatment. This controlled environment allows for gentler crosslinking protocols that maintain tissue biocompatibility while achieving long-term structural 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 approach improves tissue stability, reduces calcification, and enhances biocompatibility by minimizing glutaraldehyde polymerization, resulting in more flexible and durable crosslinked tissue that maintains the natural shape of the anatomy, thus improving the longevity and functionality of bioprosthetic devices.
Implementation Method 1
crosslinking tissue with a dialdehyde crosslinking agent under a low oxygen atmosphere
Implementation Method 2
crosslinking tissue with a dialdehyde crosslinking agent under a low oxygen atmosphere, wherein the dialdehyde crosslinking agent is provided in a substantially unpolymerized state
Data Source
AI summary
Tissue processing techniques are described involving association of tissue with a form under pressure to more precisely adapt the crosslinked tissue to the form. Pressure can be applied through holding of the issue on a porous form with suction on the form maintain tight adherence of the tissue on the form. In some embodiments, the tissue on the form is placed with the crosslinking solution in a bag that is then vacuum sealed to have the evacuated bag hold the tissue on the form. Whether or not the tissue is crosslinked on a form, glutaraldehyde can be used for crosslinking in a substantially unpolymerized state to achieve distinct crosslinked tissue properties.