Temperature-Responsive Cell Sheet for Cartilage Repair

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Solution Overview

Problem

Current methods for cartilage repair, such as tissue regeneration engineering, face challenges in developing effective cell sheets for transplantation that are suitable for cartilage repair, particularly in maintaining the phenotype of cartilage tissue and avoiding immune reactions.

Innovation Solution

A cell sheet is produced by culturing cells derived from cartilage tissue on a temperature-responsive polymer membrane, where the culturing is stopped before positivity for type II collagen immunostaining, and continued until positivity for type I collagen and aggrecan immunostaining, with specific conditions to ensure the sheet is negative for safranin O staining, maintaining basement membrane-like proteins, and having a controlled cell density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cells are cultured for extended periods to develop cartilage tissue characteristics, then the cartilage phenotype is improved, but type II collagen production increases causing immune rejection

Engineering Contradiction:
Improvecartilage repair effectivenessVSAvoidimmune reaction
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-culturing chondrocytes to express cartilage-specific markers (type I collagen and aggrecan) before transplantation, but stopping the culture before type II collagen accumulates to immunogenic levels. This timing control allows the cells to be primed for cartilage regeneration while avoiding the harmful immune response triggered by mature cartilage matrix components.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If cells are cultured to produce sufficient cartilage matrix components, then cartilage tissue formation is improved, but the structural phenotype deviates from native cartilage

Engineering Contradiction:
Improvecartilage matrix componentsVSAvoidcartilage tissue phenotype
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by precisely controlling the culture duration and monitoring specific biochemical markers (type I collagen, aggrecan, and type II collagen expression levels). By adjusting the culture parameters to stop at the optimal time point, the cells produce sufficient cartilage matrix components for tissue formation while maintaining the appropriate phenotypic characteristics without excessive type II collagen that would alter the structural composition unfavorably.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If chondrocytes are transplanted to cartilage defects, then cartilage regeneration is promoted, but immune reactions occur reducing treatment efficacy

Engineering Contradiction:
Improvecartilage regeneration rateVSAvoidtreatment consistency
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-conditioning chondrocytes in culture to express cartilage-specific phenotypic markers before transplantation. This preliminary preparation ensures that the transplanted cells are primed for regeneration (improving productivity) while the controlled culture duration prevents type II collagen accumulation that would trigger immune rejection (maintaining reliability). The consistent application of this timing protocol across treatments ensures reproducible outcomes.

Inventive Principle:
Principle #10Preliminary action

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 resulting cell sheet is suitable for cartilage repair, promoting regeneration and integration without immune reactions, maintaining structural integrity, and adhering effectively to the affected area, thus enhancing cartilage repair outcomes.

Implementation Method 1

a temperature-responsive polymer being immobilized on the surface

Methodology Applied
Scientific EffectTemperature-responsive phase change: Phase Change

Data Source

PatentUS20240358894A1Cultured cell sheet for tissue regeneration, production method thereof, and application method thereof
Publication Date: 2024.10.31 CELLSEED
  • US20240358894A1 patent drawing

AI summary

Provided is a cell sheet suitable for cartilage repair. The present invention provides a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the cell sheet is negative for immunostaining using an antibody against type II collagen. The present invention also provides a method for producing a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the method includes culturing cells derived from a cartilage tissue on a surface of a membrane, where a temperature-responsive polymer is immobilized on the surface, to give the cell sheet. The culturing is stopped before the cell sheet becomes positive for immunostaining using an antibody against type II collagen.