Dried Biological Heart Valve Toughness via Elastin Cross-Linking

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Solution Overview

Problem

Existing biological heart valves require preservation in glutaraldehyde solution, leading to increased calcification and toxicity, and have insufficient toughness for pre-loading in delivery systems, complicating surgery and increasing risks.

Innovation Solution

A method involving soaking fresh animal pericardium in an aqueous solution of soluble elastin or glycosaminoglycan, followed by cross-linking reactions with carbodiimide or N-hydroxysuccinimide and glutaraldehyde, and subsequent drying to create a pre-loadable dried biological heart valve with improved toughness.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If biological valve is preserved in glutaraldehyde solution, then the valve can be stored for long time, but the valve contains residual glutaraldehyde which increases calcification and toxicity

Engineering Contradiction:
Improvestorage timeVSAvoidcalcification and toxicity
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the preservation state of the biological valve from wet (in glutaraldehyde solution) to dry. The valve is crosslinked with glutaraldehyde, then dried to remove the solution, achieving long-term storage without residual glutaraldehyde that causes calcification and toxicity. This parameter change from wet to dry state resolves the contradiction between storage duration and harmful residues.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If biological valve is crimped and loaded into delivery system at operation site, then the valve can be used, but the preparation process is cumbersome and increases operation time

Engineering Contradiction:
Improveease of valve preparationVSAvoidoperation time
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-crimping and pre-loading the biological valve into the delivery system during the manufacturing process, before sterilization and storage. The valve is crosslinked, dried, and loaded in advance. At the operation site, only simple deployment is needed, eliminating cumbersome preparation steps and reducing operation time.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If dried biological valve is pre-loaded in delivery system, then the surgical process is simplified, but the valve must withstand long time mechanical crimping and is prone to crimping damage

Engineering Contradiction:
Improveease of surgical processVSAvoidresistance to crimping damage
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by performing the crosslinking process before loading the valve into the delivery system. The biological valve is crosslinked with glutaraldehyde to enhance its mechanical strength and toughness, then dried and loaded. This preliminary strengthening ensures the valve can withstand long-term mechanical crimping without damage, resolving the contradiction between ease of surgical process and reliability.

Inventive Principle:
Principle #10Preliminary action

4Stability of the object's composition

If biological valve is crosslinked by glutaraldehyde, then the valve structure is stabilized, but the valve requires washing and has insufficient toughness for pre-loading

Engineering Contradiction:
Improvestructural stabilityVSAvoidtoughness
Core Design Contradiction:
Stability of the object's compositionVSStrength

Solution Approach 1:

The patent applies continuity of useful action by extending the crosslinking process. After initial crosslinking with glutaraldehyde to stabilize structure, the valve undergoes additional crosslinking with carbodiimide and N-hydroxysuccinimide to further enhance toughness. This continuous crosslinking process achieves both structural stability and sufficient toughness for pre-loading applications.

Inventive Principle:
Principle #20Continuity of useful action

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 enhances the toughness of the biological valve, allowing it to withstand mechanical crimping and simplifies the surgical process by eliminating the need for glutaraldehyde preservation, reducing calcification and toxicity risks.

Implementation Method 1

The carboxyl group contained in the elastin or glycosaminoglycan can be chemically cross-linked with the amino group in the fresh pericardium in the mixed solution of carbodiimide or N-hydroxysuccinimide to form an amide bond after dehydration condensation

Methodology Applied
Scientific EffectDehydration condensation:

Implementation Method 2

subjecting the pericardium to a first cross-linking reaction in a mixed solution of carbodiimide or N-hydroxysuccinimide to allow the soluble elastin or glycosaminoglycan to bind to the pericardium via a chemical bond

Methodology Applied
Scientific EffectChemical cross-linking: Chemical Bonding

Implementation Method 3

subjecting the pericardium after the first cross-linking to a second cross-linking reaction in an aqueous glutaraldehyde solution

Methodology Applied
Scientific EffectChemical cross-linking: Chemical Bonding

Implementation Method 4

drying the pericardium after the second cross-linking, to obtain the pre-loadable dried biological heart valve

Methodology Applied
Scientific EffectDrying: Evaporation

Data Source

PatentUS12064531B2Pre-Loadable Dried Biological Heart Valve and Preparation Method Thereof
Publication Date: 2024.08.20 VENUS MEDTECH (HANGZHOU) INC

AI summary

A pre-loadable dried biological heart valve and a preparation method thereof. The preparation method includes: Step A: soaking a fresh animal pericardium in an aqueous solution of soluble elastin or glycosaminoglycan, and then subjecting the pericardium to a first cross-linking reaction in a mixed solution of carbodiimide or N-hydroxysuccinimide to allow the soluble elastin or glycosaminoglycan to bind to the pericardium via a chemical bond; and Step B: subjecting the pericardium after the first cross-linking to a second cross-linking reaction in an aqueous glutaraldehyde solution, and then drying the pericardium after the second cross-linking, to obtain the pre-loadable dried biological heart valve. The dried biological heart valve obtained by the above preparation method has good toughness, and is rapidly flattened out in a simulated folding and pressing test.