Functionalized Biological Matrices for Glutaraldehyde-Free Dry Valves

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Solution Overview

Problem

Existing biological heart valves cross-linked with glutaraldehyde suffer from issues such as poor mechanical properties, calcification, toxicity, and complex preparation procedures due to residual aldehyde groups, leading to short service life and increased surgical risks.

Innovation Solution

A method involving the use of 3-sulfopropyl methacrylate to introduce a polymer network into biological matrix materials, forming stable crosslinks and functional groups, which improves biocompatibility and reduces calcification by using radical polymerization without glutaraldehyde, allowing for a non-glutaraldehyde preloadable dry biological valve material.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If glutaraldehyde crosslinking is used, then simple process and low cost are achieved, but elastin cannot be protected and mechanical properties decline

Engineering Contradiction:
Improvecrosslinking process simplicityVSAvoidmechanical properties
Core Design Contradiction:
Ease of manufactureVSStrength

Solution Approach 1:

The patent changes the crosslinking parameters by using different crosslinking agents (carbodiimide, polyepoxy, genipin) with varying chemical properties and reaction mechanisms to achieve better elastin protection and mechanical property preservation while maintaining process feasibility

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite crosslinking strategies by combining multiple crosslinking agents or methods (e.g., carbodiimide with polyepoxy, or genipin with additional treatments) to create a multi-functional crosslinked structure that protects elastin while maintaining mechanical strength

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If glutaraldehyde crosslinking is used, then stable collagen structure is achieved, but residual aldehyde groups cause calcification problems

Engineering Contradiction:
Improvecollagen structure stabilityVSAvoidcalcification risk
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful aldehyde groups from the crosslinking process by replacing glutaraldehyde with alternative crosslinking agents (carbodiimide, polyepoxy, genipin) that do not leave residual toxic groups, thereby eliminating the calcification risk while maintaining collagen stability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the harmful effect of residual aldehyde groups into a beneficial outcome by using crosslinking agents that not only provide stable collagen structure but also prevent calcification through their unique chemical properties, turning the crosslinking process into a dual-benefit treatment

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Object-affected harmful factors

If genipin crosslinking is used, then toxicity is reduced, but long-term stability and mechanical properties are inferior

Engineering Contradiction:
ImprovetoxicityVSAvoidservice life
Core Design Contradiction:
Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The patent merges multiple crosslinking methods (carbodiimide, polyepoxy, genipin) into a composite crosslinking system where each agent contributes its strengths: carbodiimide for stable amide bonds, polyepoxy for versatile crosslinking, and genipin for low toxicity, achieving both reduced toxicity and enhanced long-term stability

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent develops a universal crosslinking system that can adapt to different biological matrix requirements by selecting and combining appropriate crosslinking agents, providing both low toxicity and long-term mechanical stability through multi-functional crosslinking strategies

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

4Stability of the object's composition

If glutaraldehyde immersion is used for preservation, then product stability is achieved, but complex preparation procedures and surgical risks increase

Engineering Contradiction:
Improveproduct stabilityVSAvoidpreparation procedure complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the need for glutaraldehyde immersion preservation by incorporating alternative crosslinking agents directly into the manufacturing process, creating inherently stable products that do not require toxic preservatives and complex pre-operative washing procedures

Inventive Principle:
Principle #2Taking out (Extraction)

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 mechanical properties and biocompatibility of biological matrix materials, reduces calcification, and simplifies the preparation process by eliminating the need for glutaraldehyde, resulting in a stable and rapidly flattening dry valve material.

Implementation Method 1

adding an initiator to initiate polymerization, to realize the crossinking and functionalization of the biological matrix material

Methodology Applied
Scientific EffectRadical polymerization: Photopolymerisation

Implementation Method 2

the sulfonic acid group can improve the hydrophilicity, so that the dry film being released can quickly absorb water and recover to be flattened in the human environment

Methodology Applied
Scientific EffectHydrophilicity: Hydrophile

Data Source

PatentEP4108265B1Functionalized biological matrix material, preparation method therefor and use thereof
Publication Date: 2025.09.03 VENUS MEDTECH (HANGZHOU) INC
  • EP4108265B1 patent drawingFigure 1~2
  • EP4108265B1 patent drawingFigure 3~4

AI summary

Disclosed are a functionalized biological matrix material, a preparation method therefor and use thereof, which belong to the technical field of medical materials. In the present invention, by means of the hybridization of a biological matrix material with 3-sulfopropyl methacrylate, the cross-linking and functionalization of the biological matrix material are achieved at the same time. A specific method comprises modifying carbon-carbon double-bond structures such as allyl, methallyl in a biological matrix material, immersing the biological matrix material in an aqueous solution containing 3-sulfopropyl methacrylate, and finally performing cross-linking and functionalization on the biological matrix material by means of radical polymerization, and using the biological matrix material to prepare materials such as valves. The present invention achieves multi-site and long-range cross-linking of a biological matrix material by means of a polymer network, and at the same time introduces corresponding functional functional groups so as to achieve functionalization of the biological matrix material.