3D Cellular Tissue Production via Gelation

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Solution Overview

Problem

Existing methods for producing three-dimensional cellular tissues struggle to maintain target cells at predetermined positions, making it difficult to construct tissues that require structural control and evaluate properties like cancer cell migration and drug sensitivity effectively.

Innovation Solution

A method involving the creation of stromal and target cell-containing mixtures with cationic substances, extracellular matrix components, and polyelectrolytes, which are gelled and then incubated together to form three-dimensional cellular tissues, allowing for precise control over cell positioning and tissue structure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to produce three-dimensional cellular tissues, then the production process is simple, but the target cells cannot be maintained at predetermined positions and structural control is lost

Engineering Contradiction:
Improvecell positioning precisionVSAvoidproduction process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The production method is segmented into distinct sequential steps: obtaining stromal cell-containing mixture, gelling to form first gel composition, obtaining target cell-containing mixture, placing in contact, gelling to form second gel composition, and incubating. This segmentation allows precise control at each stage while maintaining overall process manageability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The stromal cell-containing mixture is prepared and gelled in advance to form the first gel composition before introducing the target cells. This preliminary action creates a structured foundation that enables subsequent precise positioning and structural control of the target cells during the incubation phase.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If complex gelation processes are used to control tissue structure, then structural control is improved, but the production time and process complexity increase

Engineering Contradiction:
Improvetissue structural controlVSAvoidproduction time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The gelation process utilizes parameter changes (temperature, pH, ionic strength) to trigger gel formation from the cell-containing mixtures. By controlling these parameters, the method achieves precise tissue structural control during incubation while maintaining efficient production timing, as the gelation occurs in situ during the incubation period rather than requiring separate extended processing steps.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If simple cell mixture methods are used, then the production process is quick, but the tissue cannot maintain structural complexity during prolonged culture

Engineering Contradiction:
Improveculture periodVSAvoidtissue structural stability
Core Design Contradiction:
Duration of action of stationary objectVSStability of the object's composition

Solution Approach 1:

The method creates a composite three-dimensional cellular tissue structure by combining stromal cells and target cells within a gel matrix formed from extracellular matrix components and polyelectrolytes. This composite structure provides the mechanical stability and architectural framework necessary to maintain tissue structural integrity during prolonged culture periods, enabling long-term studies of cell behavior and tissue development.

Inventive Principle:
Principle #40Composite 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

This approach enables the construction of tissues with controlled structural complexity, allowing for prolonged culture periods and efficient evaluation of cell behavior, such as cancer cell migration and drug sensitivity, facilitating advanced drug screening and modeling.

Implementation Method 1

a cationic substance, an extracellular matrix component and a polyelectrolyte

Methodology Applied
Scientific EffectElectrostatic attraction: Ion Repulsion/Attraction

Implementation Method 2

gelling the stromal cell-containing mixture to obtain a first gel composition

Methodology Applied
Scientific EffectGelation: Gel

Data Source

PatentUS20240174982A1Methods of producing three-dimensional cellular tissues, and three-dimensional cellular tissues
Publication Date: 2024.05.30 TOPPAN INC
  • US20240174982A1 patent drawing
  • US20240174982A1 patent drawing
  • US20240174982A1 patent drawing

AI summary

A method of producing three-dimensional cellular tissues includes: obtaining a stromal cell-containing mixture containing stromal cells, a cationic substance, an extracellular matrix component and a polyelectrolyte, or a stromal cell-containing mixture containing stromal cells, a cationic substance and a fragmented extracellular matrix component; gelling the stromal cell-containing mixture to obtain a first gel composition containing stromal cells; obtaining a target cell-containing mixture containing target cells, a cationic substance, an extracellular matrix component and a polyelectrolyte, or a target cell-containing mixture containing target cells, a cationic substance and a fragmented extracellular matrix component; placing the target cell-containing mixture in contact with the first gel composition; gelling the target cell-containing mixture to obtain a second gel composition containing target cells; and incubating the first gel composition and the second gel composition to obtain three-dimensional cellular tissues.