Modified Gelatin Hydrogels via Thiol-Michael Addition

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Solution Overview

Problem

Existing hydrogel formation methods, particularly photoinitiated radical polymerization, face challenges such as inhomogeneous mechanical properties, optical turbidity, and cell viability issues due to high light exposure requirements.

Innovation Solution

The use of modified recombinant gelatins with thiol groups, formed through a thiol-Michael addition reaction without photoinitiators, to create hydrogels with improved mechanical homogeneity and cell compatibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If photoinitiated radical polymerization with (meth)acrylates is used to form hydrogels, then the hydrogel network is formed through chain-growth mechanism, but the resulting network is inhomogeneous and exhibits post-crosslinking shrink and optical turbidity

Engineering Contradiction:

Improvehydrogel formation speedVSAvoidnetwork homogeneity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent changes the fundamental polymerization mechanism from chain-growth to step-growth by switching from (meth)acrylate chemistry to thiol-ene chemistry. This parameter change in reaction mechanism transforms the network formation process, eliminating the inhomogeneity and shrinkage issues associated with chain-growth polymerization while maintaining efficient hydrogel formation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the chain-growth polymerization mechanism with a step-growth mechanism. This mechanistic substitution fundamentally changes how the network forms: instead of rapid chain propagation causing inhomogeneity, the step-growth mechanism allows gradual, uniform network development through sequential bond formation between thiol and ene groups, eliminating post-crosslinking shrink and turbidity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Strength

If high intensity light exposure is used in photopolymerization, then the hydrogel rigidity increases and optical transparency improves, but cell viability is compromised

Engineering Contradiction:

Improvehydrogel rigidityVSAvoidcell viability

Core Design Contradiction:

StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent replaces photopolymerization with a thiol-Michael addition reaction that does not require high-intensity light exposure. This substitution eliminates the harmful UV light exposure to cells while still achieving hydrogel formation with appropriate mechanical properties through the thiol-ene crosslinking mechanism.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces a thiol-Michael addition reaction as an intermediary process between gelatin modification and hydrogel formation. This intermediary chemical reaction pathway allows network formation without direct high-energy UV exposure, protecting encapsulated cells from damage while still achieving the desired crosslinked hydrogel structure.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If natural gelatins are used to provide cell interaction sites, then bio-functionality is improved, but mechanical properties become weaker due to broad mesh size distribution

Engineering Contradiction:

Improvecell interaction capabilityVSAvoidmechanical properties

Core Design Contradiction:

ReliabilityVSStrength

Solution Approach 1:

The patent creates a composite system by chemically modifying gelatin with thiol groups and combining it with ene-containing crosslinkers. This composite approach merges the biofunctionality of gelatin with the mechanical strength provided by the controlled thiol-ene crosslinked network, achieving both cell interaction capability and improved mechanical properties.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent changes the molecular structure of gelatin by introducing thiol groups at specific positions through chemical modification. This structural parameter change allows controlled crosslinking density and mesh size distribution, transforming the weak natural gelatin into a material with both preserved biofunctionality and enhanced mechanical strength through uniform network formation.

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

The modified gelatin hydrogels exhibit enhanced mechanical properties, reduced variability in cell response, and improved stability against protein and growth factor degradation, making them suitable for various biomedical applications.

Implementation Method 1

The use of modified recombinant gelatins with thiol groups, formed through a thiol-Michael addition reaction without photoinitiators, to create hydrogels

Methodology Applied

Scientific EffectThiol-Michael addition reaction: Chemical Bonding

Data Source

PatentEP4172190B1Modified gelatins

Publication Date: 2025.01.29 FUJIFILM CORP

Figure 1~2

AI summary

A modified gelatin comprising: (a) lysine residues; and (b) lysine residues comprising a pendent side chain carrying a thiol group; wherein the modified gelatin comprises at least 50μmoles/g of component (b) and at least 450μmoles/g in total components (a) and (b). Also claimed are hydrogels, a process for making modified gelatins and kits comprising the modified gelatins and a crosslinking agent.