Dry Biological Tissue Preparation for Anti-Calcification and Low Immunity

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Solution Overview

Problem

Biological tissues used in clinical practice face issues such as valvular calcification and toxicity due to residual glutaraldehyde, and existing decellularization methods lead to immune responses and structural degradation.

Innovation Solution

A method involving cross-linking, decellularization with gradually increasing concentration solutions, dissolving phospholipid impurities, removing carboxyl groups, and protecting aldehyde groups, followed by dehydration with decreasing concentration solutions, culminating in anaerobic packaging and sterilization to produce an anti-immune, anti-calcification dry biological tissue material.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If biological tissue is cross-linked and stored in dilute aqueous solutions containing glutaraldehyde, then the tissue remains hydrated and sterile, but residual glutaraldehyde promotes valvular calcification and produces toxicity

Engineering Contradiction:
Improvesterility and hydration maintenanceVSAvoidcalcification and toxicity from residual glutaraldehyde
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the harmful glutaraldehyde from the biological tissue through repeated extensive washing with dilute aqueous solutions, thereby eliminating the source of calcification and toxicity while maintaining the tissue's structural integrity

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the concentration parameter of glutaraldehyde in the storage solution from a higher cross-linking concentration to a dilute concentration (0.01-2% w/v), allowing the tissue to remain hydrated and sterile while minimizing residual glutaraldehyde that causes harmful effects

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If biological tissue undergoes decellularization treatment to reduce immunogenicity, then immune responses are reduced, but insufficient decellularization leaves immune-responsive components while excessive decellularization destroys collagenous structure

Engineering Contradiction:
ImproveimmunogenicityVSAvoidcollagenous structural integrity
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The invention applies partial decellularization using controlled concentrations of decellularization solutions (e.g., 0.1-5% w/v detergent) for specific time periods, removing sufficient immunogenic components while preserving the collagenous framework through carefully optimized treatment parameters

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The invention optimizes decellularization parameters including solution concentration, treatment time, and temperature to achieve the optimal balance between removing immunogenic components and preserving structural integrity, using multiple washing steps to control the degree of decellularization

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If medical personnel perform extensive washing to remove glutaraldehyde before implantation, then calcification and toxicity are reduced, but the preparatory work increases time required and exposure risk

Engineering Contradiction:
Improveresidual glutaraldehyde removalVSAvoidpreparatory work time and contamination exposure
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The invention performs preliminary removal of glutaraldehyde during the manufacturing process through repeated washing steps, so that the biological tissue can be stored in a ready-to-use state with minimal residual glutaraldehyde, eliminating the need for extensive pre-operative preparation and reducing surgical time and contamination risk

Inventive Principle:
Principle #10Preliminary action

4Object-affected harmful factors

If phospholipids remain on the surface of implanted biological materials, then they may adsorb lipoproteins and calcium-binding proteins, but removing phospholipids through excessive decellularization causes structural destruction

Engineering Contradiction:
Improvecalcification from phospholipid adsorptionVSAvoidmechanical strength and structural integrity
Core Design Contradiction:
Object-affected harmful factorsVSStrength

Solution Approach 1:

The invention selectively removes phospholipids from the surface regions of the biological tissue through controlled decellularization and detergent treatment, while preserving the bulk collagenous structure, thereby reducing calcification risk without compromising overall mechanical strength

Inventive Principle:
Principle #3Local quality

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 results in a dry biological tissue material with high anti-calcification performance, low immune activation, and good mechanical properties, facilitating easy storage and use while reducing contamination risks.

Implementation Method 1

performing a first anti-calcification treatment on the biological tissue material using a dissolving solution, wherein the dissolving solution is used to dissolve phospholipid impurities in the biological tissue

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

performing a third anti-calcification treatment on the biological tissue material using a reducing solution, wherein the reducing solution is used to protect free aldehyde groups

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentEP4268858B1Biological tissue material and preparation method therefor
Publication Date: 2025.12.17 JIANGSU TRULIVE MEDTECH CO LTD
  • EP4268858B1 patent drawingFigure 1~2
  • EP4268858B1 patent drawingFigure 3

AI summary

The present invention discloses a dry biological tissue material and a method of preparing the material. The method includes: performing a decellularization treatment on the biological tissue material using decellularization solutions, wherein the decellularization solutions include first to N-th decellularization solutions with gradually increasing concentrations; performing a first anti-calcification treatment on the biological tissue material using a dissolving solution, wherein the dissolving solution is used to dissolve phospholipid impurities in the biological tissue; performing a second anti-calcification treatment on the biological tissue material using a removal solution, wherein the removal solution is used to remove carboxyl groups produced in the cross-linking and decellularization treatments as a result of oxidation of aldehyde groups; performing a third anti-calcification treatment on the biological tissue material using a reducing solution, wherein the reducing solution is used to protect free aldehyde groups; and performing a dehydration treatment on the biological tissue material using dehydrating solutions, wherein the dehydrating solutions include first to M-th dehydrating solutions with gradually increasing concentrations, and wherein the concentration of the M-th dehydrating solution is lower than the concentration of the N-th decellularization solution. The three anti-calcification treatments respectively for dissolving phospholipids, removing carboxylic acids and protecting aldehyde groups make up a complete anti-calcification process, thereby achieving a high anti-calcification performance.