In Situ Forming Hydrogel Linker Design for Biostability

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

In situ forming hydrogels face challenges with poor mechanical strength and biostability due to direct phenol moiety bonding, leading to high viscosity and cytotoxicity issues, limiting their biomedical applications.

Innovation Solution

Introducing a hydrophilic polymer chain as a linker between a polymer backbone and phenol or aniline moieties to enhance solubility and reactivity, allowing for improved mechanical strength and biostability through dehydrogenation reactions mediated by horseradish peroxidase and hydrogen peroxide.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If direct phenol moiety bonding is used for in situ forming hydrogel, then crosslinking is achieved, but mechanical strength and biostability are poor

Engineering Contradiction:
Improvemechanical strengthVSAvoidbiostability
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent introduces a hydrophilic polymer chain as an intermediary linker between the polymer backbone and phenol/aniline moieties. This linker mediates the crosslinking process by providing a solubility-enhancing segment that allows better mixing and reaction, while the phenol/aniline groups maintain crosslinking capability. The linker acts as a bridge that improves both solubility and the quality of crosslinking, resolving the contradiction between achieving crosslinking and maintaining mechanical strength/biostability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite structure at the molecular level by combining a hydrophilic polymer chain with phenol or aniline moieties attached to a polymer backbone. This composite molecular architecture integrates the solubility benefits of hydrophilic polymers with the crosslinking capabilities of phenol/aniline groups, resulting in a material that achieves both good processability and enhanced mechanical strength and biostability.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If direct phenol moiety bonding is used, then crosslinking occurs, but viscosity becomes high making uniform mixing difficult

Engineering Contradiction:
ImprovecrosslinkingVSAvoiduniform mixing
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The hydrophilic polymer chain serves as a mediator that improves the processability of the polymer solution. By introducing this soluble segment, the overall viscosity of the solution is reduced, enabling uniform mixing of cells and drugs while maintaining the crosslinking functionality of the phenol/aniline moieties. The intermediary allows the system to be processed easily before crosslinking occurs.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical structure parameters of the polymer by incorporating hydrophilic segments with appropriate molecular weight and composition. This parameter change affects the solution viscosity and solubility characteristics, making the polymer solution easier to handle and mix uniformly while preserving the crosslinking reactivity of the attached phenol or aniline groups.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If phenol-phenol coupling is used for crosslinking, then gelation occurs, but reactivity control is limited leading to poor stability

Engineering Contradiction:
Improvegelation rateVSAvoidgel stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The hydrophilic polymer chain acts as a reactive intermediary that enhances and controls the phenol-phenol coupling reaction. The linker provides a favorable microenvironment for the crosslinking reaction, improving reactivity and allowing better control over gelation kinetics. This leads to more stable gels with controlled degradation properties, as the crosslinking can be optimized without sacrificing stability.

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 hydrogel exhibits enhanced solubility, reactivity, and mechanical strength, enabling effective biomedical applications such as tissue regeneration and drug delivery with controlled gelation and degradation properties.

Implementation Method 1

dehydrogenation reactions mediated by horseradish peroxidase and hydrogen peroxide

Methodology Applied
Scientific EffectDehydrogenation reaction: Oxidation

Implementation Method 2

dehydrogenation reactions mediated by horseradish peroxidase and hydrogen peroxide

Methodology Applied
Scientific EffectEnzyme-mediated oxidation: Enzyme

Implementation Method 3

Introducing a hydrophilic polymer chain as a linker between a polymer backbone and phenol or aniline moieties to enhance solubility

Methodology Applied
Scientific EffectHydrophilic interaction: Hydrophile

Implementation Method 4

hydrogels have been extensively studied as biomaterials to be used in various biomedical applications

Methodology Applied
Scientific EffectHydrogel water retention: Hydrogel

Data Source

PatentEP2448610B1In situ forming hydrogel and biomedical use thereof
Publication Date: 2016.01.06 AJOU UNIV IND ACADEMIC COOP FOUND
  • EP2448610B1 patent drawingFigure 1~3
  • EP2448610B1 patent drawingFigure 4~6
  • EP2448610B1 patent drawingFigure 7~8

AI summary

Disclosed are in situ-forming injectable hydrogel and medical uses thereof. In the in situ-forming injectable hydrogel two or more homogeneous or heterogeneous polymers are bonded to each other by a dehydrogenation reaction between phenol or aniline moieties on adjacent polymers, wherein a polymer backbone is grafted with a phenol or aniline moiety using a linker. In contrast to conventional hydrogel, the in situ-forming injectable hydrogel is superior in terms of in vivo stability and mechanical strength thanks to the introduction of a water-soluble polymer as a linker which leads to an improvement in the reactivity of phenol or aniline moieties. Having the advantage of superior biostability and mechanical strength, the hydrogel finds a variety of applications in the biomedical field.