Solid-State Biopolymer Crosslinking Without Solvent Deformation

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Solution Overview

Problem

Conventional methods for chemically modifying biopolymers, such as gelatin, often require dissolution in solvents, leading to structural deformation and limited crosslinking strength, especially when using toxic agents like glutaraldehyde, and struggle to achieve high degrees of crosslinking without compromising the biopolymer's properties.

Innovation Solution

A method involving a chemical reaction between a solid biopolymer structure and a solid-state crosslinking agent, like transglutaminase or carbodiimide, at high humidity (50% or more) to achieve crosslinking without solvent dissolution, utilizing enzymes or condensation agents with a melting point of 50°C or more.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If biopolymers are chemically modified by dissolving in solvents, then chemical modification can proceed, but the biopolymer structure becomes deformed and physical strength is lost

Engineering Contradiction:
Improvechemical modificationVSAvoidstructural deformation
Core Design Contradiction:
Ease of manufactureVSShape

Solution Approach 1:

The invention changes the physical state parameters of the reactants from liquid/dissolved state to solid state. By using solid biopolymer and solid crosslinking agent, the reaction proceeds without solvent dissolution, thereby preventing structural deformation while enabling chemical modification.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Humidity acts as an intermediary medium that enables the chemical reaction between solid biopolymer and solid crosslinking agent. The high humidity environment (50% or more) provides the necessary water molecules for the reaction to proceed without dissolving the biopolymer structure.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Strength

If glutaraldehyde is used as a crosslinking agent, then crosslinking can occur, but the biopolymer may become toxic and lose its biological properties

Engineering Contradiction:
Improvecrosslinking strengthVSAvoidtoxicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The invention replaces persistent toxic crosslinking agents like glutaraldehyde with biocompatible alternatives such as transglutaminase enzyme or carbodiimide. These agents achieve crosslinking without introducing long-term toxic residues, making them suitable for medical applications.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention converts the limitation of solid-state reactivity into an advantage by using biocompatible crosslinking agents that require specific environmental conditions (high humidity) to activate. This ensures safe crosslinking without toxic byproducts while maintaining biological functionality.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Shape

If transglutaminase crosslinking is performed at low temperatures to prevent gelatin dissolution, then structural deformation is avoided, but crosslinking efficiency is significantly reduced

Engineering Contradiction:
Improvestructural integrityVSAvoidcrosslinking efficiency
Core Design Contradiction:
ShapeVSProductivity

Solution Approach 1:

The invention adds the humidity dimension to the temperature-control strategy. By operating at high humidity (50% or more), the system enables efficient enzymatic crosslinking at low temperatures without gelatin dissolution, as the high humidity environment facilitates enzyme activity while the low temperature prevents structural deformation.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The invention changes the environmental parameters from temperature-only control to combined temperature and humidity control. This dual-parameter approach allows the system to achieve both structural integrity and crosslinking efficiency by operating at low temperature with high humidity.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If biopolymers are used in solid form, then biological safety is maintained, but physical strength is insufficient for chemical modification

Engineering Contradiction:
Improvebiological safetyVSAvoidphysical strength
Core Design Contradiction:
Object-affected harmful factorsVSStrength

Solution Approach 1:

Humidity serves as an intermediary that enables chemical reactions in solid biopolymers without compromising biological safety. The high humidity environment activates the crosslinking reaction while the solid-state structure maintains biological compatibility and physical integrity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the reaction conditions from requiring dissolution (liquid state) to enabling reaction in solid state through high humidity. This parameter change allows solid biopolymers to undergo chemical modification while maintaining both physical strength and biological safety.

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 approach minimizes solvent use, maintains the biopolymer's form, prevents pharmaceutical agent elution, and enables efficient high-strength crosslinking of biopolymers, overcoming the limitations of traditional methods by allowing crosslinking at low temperatures without structural deformation.

Implementation Method 1

A known enzyme used for crosslinking collagen and gelatin is transglutaminase. Transglutaminase is an enzyme that allows glutamine residues and lysine residues to bond with each other.

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

reacting, at a humidity of 50% or more, a solid structure obtained from a biopolymer with a solid-state compound having a melting point of 50°C or more

Methodology Applied
Scientific EffectChemical reaction in solid state: Chemical Bonding

Data Source

PatentEP2100914B1Method for producing modified biopolymer and method for crosslinking biopolymers
Publication Date: 2019.07.24 FUJIFILM CORP

AI summary

It is an object of the present invention to provide a method wherein a structure which was prepared with a biopolymer such as gelatin is chemically modified with the use of a low-volatile chemical substance without dissolution of gelatin, and a biopolymer crosslinking method for producing a biopolymer having high strength (a high degree of crosslinking). The present invention provides a method for producing a modified biopolymer, which comprises reacting a structure prepared with a biopolymer with a solid-state compound having a melting point of 50°C or more at a humidity of 50% or more, and a method for crosslinking biopolymer which comprises treating a biopolymer with a crosslinking agent, wherein the crosslinking agent concentration in a reaction mixture is 1.0% to 10% by weight and crosslinking is carried out in the presence of an organic fluorine compound.