Biological Tissue Detoxification for Prosthetic Valves

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Solution Overview

Problem

Biological tissues used in prosthetic valves undergo calcification due to residual aldehyde groups and phospholipids after glutaraldehyde fixation, leading to reduced flexibility and potential tissue laceration, which existing methods only partially address.

Innovation Solution

A method involving treatment with an aqueous solution of 1,2-octanediol and ethanol to eliminate membrane phospholipids, followed by a detoxification step using taurine or homocysteic acid at elevated temperatures to neutralize free aldehyde groups, enhancing the fixation and reducing calcification sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If glutaraldehyde fixation is used to protect tissue and prevent rejection, then tissue stability and immune compatibility are improved, but free aldehyde groups remain that create binding sites for calcium accumulation

Engineering Contradiction:
Improvetissue stabilityVSAvoidcalcification
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes the harmful free aldehyde groups from the fixed tissue through extraction with amino compounds (lysine, histidine, arginine, or their salts). These amino compounds react with and eliminate the residual aldehyde groups that would otherwise serve as binding sites for calcium, thereby preventing calcification while maintaining the beneficial cross-linking effects of glutaraldehyde fixation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces amino compounds as intermediary substances that mediate between the fixed tissue and calcium ions. These intermediaries (amino acids or their salts) bind to the free aldehyde groups, preventing calcium from attaching to these sites. This intermediary action blocks the calcification pathway without disrupting the structural stability provided by glutaraldehyde cross-linking.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Stability of the object's composition

If phospholipids are present in the tissue structure, then cellular components are maintained, but phospholipids constitute additional sites for calcium binding and accumulation

Engineering Contradiction:
Improvecellular structureVSAvoidcalcification sites
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes phospholipids from the tissue structure through extraction processes that selectively eliminate these lipid components. By extracting phospholipids, the patent eliminates the additional calcium binding sites they provide, thereby reducing calcification risk while preserving the essential collagenous structure and cellular framework necessary for tissue function.

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If multiple treatment steps are used to neutralize aldehyde residues and remove phospholipids, then calcification is partially limited, but the process complexity increases

Engineering Contradiction:
ImprovecalcificationVSAvoidtreatment process
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent combines the neutralization of free aldehyde groups and the removal of phospholipids into a single integrated treatment step. By using amino compounds that simultaneously address both issues (neutralizing aldehydes and eliminating phospholipid-related calcification sites), the patent simplifies the overall treatment process while maintaining effective calcification prevention.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent employs amino compounds with multi-functional properties that can both neutralize free aldehyde groups and address phospholipid-related calcification risks. This universal approach allows a single treatment agent to perform multiple protective functions, reducing the need for separate treatment steps and simplifying the overall processing protocol.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 significantly reduces the number of free aldehyde groups and calcification sites, resulting in biological tissues that are more resistant to calcification and have improved mechanical properties and immune compatibility.

Implementation Method 1

treatment with an elimination solution including 1,2-ocanediol and ethanol to remove membrane phospholipids

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 2

detoxification step using taurine or homocysteic acid at elevated temperatures to neutralize free aldehyde groups

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Implementation Method 3

glutaraldehyde forms intra-chain and inter-chain bridge structures, causing the cross linking of the biological tissue

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 4

treatment with a detoxifying solution including taurine or homocysteic acid at a temperature above room temperature

Methodology Applied
Scientific EffectThermal heating: Heating

Data Source

PatentUS9457130B2Method for preparing biological tissues for use in biological prostheses
Publication Date: 2016.10.04 CORCYM SRL
  • US9457130B2 patent drawing
  • US9457130B2 patent drawing
  • US9457130B2 patent drawing

AI summary

A method of treating a biological tissue for biological prostheses includes steps of fixation of the biological tissue via a fixing solution including glutaraldehyde and detoxification of the fixed biological tissue via treatment with a detoxifying solution. The detoxification step includes one or both of eliminating phospholipids via treatment with an elimination solution and a treatment with a detoxifying solution. The elimination solution includes 1,2-octanediol and ethanol. The detoxifying solution includes taurine or homocysteic acid.