3D Tissue Thickness Retention via Cationic ECM Fragmentation

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Solution Overview

Problem

The thickness of three-dimensional tissue bodies produced using existing methods decreases over time during culture, leading to a reduction in thickness.

Innovation Solution

A method involving the mixing of cells with a cationic substance and a fragmented extracellular matrix component, followed by culturing, which includes the use of a polyelectrolyte to maintain tissue thickness, utilizing components like glycosaminoglycan and fragmented collagen to enhance cell adhesion and structural integrity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If cells are cultured using conventional methods, then cell growth and proliferation occur, but the thickness of the three-dimensional tissue body decreases over time

Engineering Contradiction:
Improveculture periodVSAvoidtissue thickness
Core Design Contradiction:
Duration of action of moving objectVSLength of stationary object

Solution Approach 1:

The extracellular matrix is fragmented into small particles (average diameter 1-100 μm) to create a scaffold that better supports tissue architecture during culture, preventing thickness reduction while allowing extended culture periods

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A cationic substance acts as an intermediary between cells and the fragmented extracellular matrix, facilitating cell attachment and maintaining three-dimensional tissue structure throughout the culture period

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If the culture period is extended to allow more cell proliferation, then cell quantity increases, but tissue thickness reduction becomes more significant

Engineering Contradiction:
Improvecell quantityVSAvoidtissue thickness
Core Design Contradiction:
Quantity of substanceVSLength of stationary object

Solution Approach 1:

Fragmented extracellular matrix particles provide a distributed scaffold throughout the tissue volume, supporting cell proliferation while maintaining overall tissue thickness even during extended culture periods

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The use of fragmented extracellular matrix with specific size parameters (1-100 μm average diameter) and appropriate concentration ranges (0.01-1.0 mg/mL) creates optimal conditions for both cell growth and thickness maintenance

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 method effectively suppresses the reduction in thickness of three-dimensional tissue bodies, maintaining a thickness retention rate of 80% or higher after 4 days of culture.

Implementation Method 1

mixing a cationic substance and a fragmented extracellular matrix component with cells

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS20230323310A1Method of producing three-dimensional tissue body and three-dimensional tissue body
Publication Date: 2023.10.12 TOPPAN HOLDINGS INC
  • US20230323310A1 patent drawing

AI summary

The present invention relates to a method for producing a three-dimensional tissue body, including: a step of obtaining a mixture by mixing a cationic substance and a fragmented extracellular matrix component with cells; and a step of culturing the cells after the step of obtaining the mixture.