Glutaraldehyde-Free Cell Structure for Vascularization

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Solution Overview

Problem

Current cell structures for regenerative medicine that form blood vessels after transplantation often rely on glutaraldehyde for cross-linking, which is undesirable for human use, and there is a lack of methods to produce cell structures that can form blood vessels without glutaraldehyde.

Innovation Solution

A cell structure with biocompatible macromolecular blocks, cells, and voids, where the volume ratios of macromolecular blocks, cells, and voids are set between 10% to 30%, 20% to 50%, and 35% to 60% respectively, using recombinant peptides and cross-linking methods like heat, UV, or enzymes, without glutaraldehyde, to facilitate blood vessel formation post-transplantation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If glutaraldehyde is used for cross-linking of macromolecules in cell structure, then the structural stability and durability are improved, but the biocompatibility and safety for human transplantation deteriorate

Engineering Contradiction:
Improvestructural stabilityVSAvoidbiocompatibility
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent removes glutaraldehyde from the cell structure composition entirely, extracting the harmful cross-linking agent while maintaining structural integrity through alternative means such as physical entanglement and controlled degradation of the macromolecular blocks

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs biodegradable macromolecular blocks that can be safely degraded by the body over time, replacing permanent synthetic cross-linked structures with temporary natural materials that dissolve and are metabolized without harm

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If the cell structure is designed with sufficient thickness and uniform cell distribution, then the regenerative capacity and functional integrity are improved, but the difficulty of achieving vascularization without glutaraldehyde increases

Engineering Contradiction:
Improveregenerative capacityVSAvoidvascularization complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the cell structure into multiple macromolecular blocks distributed throughout the tissue, creating a segmented architecture that facilitates nutrient diffusion and vascular ingrowth while maintaining overall structural integrity and regenerative function

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent incorporates porous macromolecular blocks with controlled porosity that enable penetration and migration of blood vessels during regeneration, allowing capillaries to infiltrate the tissue matrix without requiring glutaraldehyde-based cross-linking

Inventive Principle:
Principle #31Porous materials

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 proposed cell structure effectively forms and maintains blood vessels over time when transplanted, particularly under the renal capsule, ensuring safe and efficient vascularization without the use of glutaraldehyde.

Implementation Method 1

cross-linking methods like heat, UV, or enzymes

Methodology Applied
Scientific EffectHeat cross-linking: Heating

Implementation Method 2

cross-linking methods like heat, UV, or enzymes

Methodology Applied
Scientific EffectUV cross-linking: Photopolymerisation

Implementation Method 3

cross-linking methods like heat, UV, or enzymes

Methodology Applied
Scientific EffectEnzymatic cross-linking: Enzyme

Implementation Method 4

freezing a solution of biocompatible macromolecules through freezing treatment

Methodology Applied
Scientific EffectFreezing: Freezing

Implementation Method 5

freeze-drying the frozen biocompatible macromolecules

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Implementation Method 6

it has been confirmed that blood vessels are formed in a cell structure, which contains a biocompatible macromolecular block and at least one kind of cell, and in which a plurality of the above-described biocompatible macromolecular blocks are arranged in gaps between a plurality of the above-described cells

Methodology Applied
Scientific EffectAngiogenesis:

Data Source

PatentUS10471180B2Cell structure and method for producing cell structure
Publication Date: 2019.11.12 FUJIFILM CORP
  • US10471180B2 patent drawing
  • US10471180B2 patent drawing
  • US10471180B2 patent drawing

AI summary

An object of the present invention is to provide a cell structure which does not contain glutaraldehyde and can form blood vessels after transplantation, and a method for producing the above-described cell structure. According to the present invention, there is provided a cell structure which contains a biocompatible macromolecular block and at least one kind of cell and has voids and in which a plurality of the biocompatible macromolecular blocks are arranged in gaps between a plurality of the cells, in which a ratio of the volume of the biocompatible macromolecular blocks with respect to the volume of the cell structure is 10% to 30%, a ratio of the volume of the cells with respect to the volume of the cell structure is 20% to 50%, and a ratio of the volume of the voids with respect to the volume of the cell structure is 35% to 60%.