Fibrin Gel Laminate for Brittle Cell Sheet Handling

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Solution Overview

Problem

Sheet-shaped cell cultures used in regenerative medicine are brittle and prone to wrinkling or tearing during isolation and operation, making them difficult to handle and implant effectively.

Innovation Solution

A method involving dripping a fibrinogen liquid onto a sheet-shaped cell culture followed by spraying a thrombin liquid to form a firm fibrin gel layer, which adheres strongly to the cells, allowing for a stable laminate that can be easily handled and implanted without the need for additional support structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a sheet-shaped cell culture is used for tissue repair, then cell transplantation efficacy is improved, but the sheet becomes brittle and prone to wrinkling or tearing during isolation and operation

Engineering Contradiction:
Improvecell transplantation efficacyVSAvoidsheet structural strength
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent creates a composite structure by forming a fibrin gel layer on the sheet-shaped cell culture. The fibrin gel acts as a supporting matrix that reinforces the brittle cell sheet, preventing tearing and wrinkling during handling while maintaining the biological functionality of the cells for tissue repair applications.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The fibrin gel serves as an intermediary support structure between the fragile cell sheet and the external handling environment. This intermediary layer provides mechanical strength during isolation and operation, yet is biocompatible and degradable, allowing the cells to function normally once implanted.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If a fibrinogen liquid and thrombin liquid are simultaneously sprayed onto a sheet-shaped cell culture to form a support layer, then the support layer is formed quickly, but the support layer may come off the sheet or cause isolation failure

Engineering Contradiction:
Improvefibrin gel formation speedVSAvoidlaminar adhesion stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies fibrinogen liquid first to the sheet-shaped cell culture, allowing it to adsorb onto the cell surface before applying thrombin liquid. This preliminary action ensures that when thrombin is added, the fibrin gel forms directly on the cell sheet with strong adhesion, preventing delamination and isolation failure while maintaining rapid gel formation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the fibrin gel formation process into two distinct steps: first applying fibrinogen, then applying thrombin. This segmentation allows each component to be optimally positioned before the reaction occurs, ensuring reliable adhesion while maintaining the benefits of rapid gel formation through the subsequent thrombin-catalyzed polymerization.

Inventive Principle:
Principle #1Segmentation

3Strength

If the support layer is thickened to prevent tearing and isolation issues, then structural stability is improved, but cell function is inhibited

Engineering Contradiction:
Improvesupport layer stabilityVSAvoidcell function
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent creates a fibrin gel layer with optimized local properties - thin enough to allow cell function and nutrient diffusion, yet sufficiently cross-linked to provide mechanical strength. The gel forms a porous network structure that offers structural support while maintaining permeability for metabolite exchange, thus supporting both structural stability and cell viability.

Inventive Principle:
Principle #3Local quality

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 laminate is strong, easy to apply, and maintains cell function, enabling reliable treatment of tissue abnormalities with improved operability and reduced need for surgical intervention.

Implementation Method 1

a fibrin gel layer formed by a reaction between fibrinogen and thrombin can firmly adhere to the sheet-shaped cell culture

Methodology Applied
Scientific EffectCoagulation: Coagulation

Data Source

PatentUS9737636B2Method for producing laminate of sheet-shaped cell culture and fibrin gel
Publication Date: 2017.08.22 TERUMO KK
  • US9737636B2 patent drawing
  • US9737636B2 patent drawing
  • US9737636B2 patent drawing

AI summary

A laminate of a sheet-shaped cell culture is disclosed, which has excellent operability and is suitable for implantation. A method is disclosed for producing a laminate of a fibrin gel and a sheet-shaped cell culture, including a step of dripping a liquid containing fibrinogen onto an upper surface of a sheet-shaped cell culture, a step of spraying a liquid containing thrombin onto the surface, and a step of forming a fibrin gel layer on the surface by a reaction between fibrinogen and thrombin; and a laminate of a fibrin gel and a sheet-shaped cell culture produced by the method are disclosed.