Tissue Shaping via Granulate and Crosslinking

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Solution Overview

Problem

Existing methods for three-dimensional shaping of tissues, such as those used in prosthetic heart valves, face challenges including inhomogeneous tissue thickness distribution, pressure peaks leading to fiber compaction, and poor crosslinking quality due to the use of rigid molded bodies on both sides.

Innovation Solution

A process using a single rigid molded body in combination with a granulate and a crosslinking agent like glutaraldehyde, where the granulate mechanically fixes the tissue and allows the crosslinking solution to penetrate, thereby avoiding pressure peaks and ensuring high crosslinking quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Shape

If rigid molded bodies are used on both sides for three-dimensional shaping, then the tissue geometry can be permanently imprinted, but pressure peaks are created causing fiber compaction and tissue stiffening

Engineering Contradiction:
Improvetissue geometryVSAvoidpressure peaks
Core Design Contradiction:
ShapeVSObject-affected harmful factors

Solution Approach 1:

The invention divides the counter-molding surface into multiple discrete granulate particles instead of using a continuous rigid surface. This segmentation allows the tissue to conform to the granulate arrangement without experiencing concentrated pressure peaks, as the load is distributed across multiple contact points rather than a continuous rigid surface.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The granulate layer creates a porous structure between the rigid molded body and the tissue. This porous arrangement allows the crosslinking solution to penetrate through to the tissue while the granulate particles themselves provide the shaping function without creating pressure peaks that would cause fiber compaction.

Inventive Principle:
Principle #31Porous materials

2Shape

If rigid molded bodies are used on both sides, then geometry imprinting is achieved, but access of crosslinking solution to tissue is obstructed

Engineering Contradiction:
Improvegeometry imprintingVSAvoidcrosslinking quality
Core Design Contradiction:
ShapeVSReliability

Solution Approach 1:

The granulate layer forms a porous intermediate structure that allows the crosslinking solution to penetrate through to the tissue. The spaces between granulate particles create channels for solution access, ensuring uniform crosslinking throughout the tissue while the outer surface of the granulate maintains the geometric imprint from the rigid molded body.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The granulate acts as an intermediary layer between the rigid molded body and the tissue. It transmits the geometric shape from the molded body to the tissue while simultaneously allowing the crosslinking solution to pass through, thus mediating between the conflicting requirements of geometry imprinting and solution access.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Shape

If rigid molded bodies are used on both sides, then three-dimensional shaping is achieved, but inhomogeneities in tissue thickness cannot be compensated

Engineering Contradiction:
Improvethree-dimensional shapingVSAvoidtissue thickness uniformity
Core Design Contradiction:
ShapeVSManufacturing precision

Solution Approach 1:

Instead of having the rigid molded body directly contact the tissue surface, the invention inverts the approach by placing the granulate layer between the molded body and the tissue. This inversion allows the granulate to adapt to tissue thickness variations while the rigid molded body maintains the overall geometric shape, thus compensating for inhomogeneities.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The granulate layer changes the mechanical parameters of the interface between the molded body and tissue. By using discrete particles with specific size and compliance properties, the system can accommodate variations in tissue thickness while maintaining consistent geometric imprinting, effectively adjusting the interface characteristics to handle thickness inhomogeneities.

Inventive Principle:
Principle #35Parameter changes

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 process enables the production of three-dimensional tissue geometries with high surface quality and homogeneous thickness distribution, reducing mechanical weak points and improving the fatigue strength of medical implants.

Implementation Method 1

the granulate mechanically fixes the tissue to be shaped to the molded body during the chemical crosslinking process

Methodology Applied
Scientific EffectMechanical fixation: Friction

Implementation Method 2

chemical crosslinking of, for example, pericardium by means of a suitable crosslinking agent, such as glutaraldehyde, leads to the formation of inter- and intramolecular bonds in the tissue

Methodology Applied
Scientific EffectChemical crosslinking: Chemical Bonding

Implementation Method 3

Due to these additional covalent bonds, the bending stiffness of the tissue increases and the tissue loses flexibility

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 4

The crosslinks that result from the chemical processing of collagen-containing tissue such as pericardium with, for example, glutaraldehyde, lead to a preservation of the elongation state currently prevailing in the tissue

Methodology Applied
Scientific EffectElongation state preservation: Elasticity

Data Source

PatentEP4559435A1Process for the three-dimensional shaping of a tissue or tissue component
Publication Date: 2025.05.28 BIOTRONIK AG
  • EP4559435A1 patent drawingFigure 1~2
  • EP4559435A1 patent drawingFigure 3~4
  • EP4559435A1 patent drawingFigure 5A~5C

AI summary

The present invention relates to a process for three-dimensional shaping of a biological and/or artificial tissue/tissue component, which enables a desired three-dimensional, reproducible and permanent shaping of the tissue/tissue component via crosslinking by means of a suitable crosslinking agent in combination with a rigid shaped body, in particular a single rigid shaped body, and a granulate.