Aqueous Gelatin Composition for Cell Sheet Handling

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Solution Overview

Problem

Current methods for storing and transferring cell sheets in regenerative medicine are hindered by the fragility of cell sheets, which are easily wrinkled and broken, and require low temperatures for storage and transfer, leading to declined cellular functions.

Innovation Solution

Development of an aqueous gelatin composition that is rapidly gelatinized at temperatures greater than or equal to 27°C and undergoes dissolution at temperatures greater than or equal to 32°C, allowing for stable storage and transfer of cell sheets without damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If cell sheets are stored and transferred at low temperatures (4°C) to maintain structural integrity, then the cell sheets are protected from breaking, but cellular functions are significantly declined

Engineering Contradiction:
Improvestructural integrity of cell sheetVSAvoidcellular function
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The invention changes the temperature parameter from low temperature (4°C) to room temperature (25°C) by developing a gelatin composition with specific gelatinization and melting points. This allows the cell sheet to be stored and transferred at room temperature without structural breakdown, while maintaining cellular function, thus resolving the contradiction between structural integrity and cellular function

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses a composite gelatin composition containing multiple types of gelatin (Type A and Type B) with specific molecular weight distributions and gelatinization temperatures. This composite material provides both structural support at room temperature and biocompatibility, enabling simultaneous achievement of structural integrity and cellular function preservation

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If ordinary gelatin with low melting point is used, then the gelatin can be melted easily at 37°C, but the gelatin is not gelatinized at room temperature (25°C) and requires temperature control below room temperature

Engineering Contradiction:
Improvemelting temperatureVSAvoidgelatinization temperature
Core Design Contradiction:
Ease of operationVSTemperature

Solution Approach 1:

The invention adjusts the gelatinization temperature parameter to be above room temperature (25°C) while keeping the melting point at or below 37°C. This is achieved by selecting gelatin types and molecular weight distributions that provide gelatinization at 27°C or higher but melting at 37°C, eliminating the need for refrigerated storage

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention exploits the phase transition properties of gelatin by carefully selecting gelatin types with specific gelatinization and melting temperatures. The gelatin composition undergoes reversible phase transition between gel and sol states at physiologically relevant temperatures, enabling room temperature storage and 37°C application without additional cooling

Inventive Principle:
Principle #36Phase transitions

3Device complexity

If cell sheets are handled without support structure, then the handling process is simple, but the fragile cell sheets are easily wrinkled and broken

Engineering Contradiction:
Improvehandling processVSAvoidmechanical strength of cell sheet
Core Design Contradiction:
Device complexityVSStrength

Solution Approach 1:

The invention creates a composite structure where the cell sheet is integrated with a gelatin support layer. The gelatin provides mechanical strength and structural support to the fragile cell sheet, preventing wrinkles and breaks during handling, while being simple to apply and remove

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The gelatin composition acts as an intermediary support structure between the fragile cell sheet and the external environment. It provides mechanical protection during handling and transfer, then can be easily removed at the destination by temperature change, simplifying the overall handling process while protecting the cell sheet

Inventive Principle:
Principle #24Intermediary (Mediator)

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 composition enables secure storage and transfer of cell sheets at room temperature, maintaining cellular viability and functionality, and can be used to create a medical laminate for supporting cell sheets during handling and application.

Implementation Method 1

rapidly gelatinized at a temperature greater than or equal to 27°C

Methodology Applied
Scientific EffectGelatinization: Phase Change

Implementation Method 2

undergoes dissolution from a gel state at a temperature greater than or equal to about 32°C

Methodology Applied
Scientific EffectDissolution: Melting

Data Source

PatentEP3366700B1Gelatin, chemically modified product thereof, aqueous composition and medical laminate containing same, production method for medical laminate, and cell sheet isolation method
Publication Date: 2021.04.07 TOKYO METROPOLITAN IND TECH RES INST
  • EP3366700B1 patent drawingFigure 1
  • EP3366700B1 patent drawingFigure 2~3
  • EP3366700B1 patent drawingFigure 4~5

AI summary

A gelatin or a chemically modified product thereof contains 10 to 50% by mass of a high-molecular weight component, and a low-molecular weight component in such an amount that a value obtained by subtracting a low-molecular weight component content from a high-molecular weight component content is greater than or equal to 0% by mass.