Carbohydrate Crosslinking of GAG Hydrogels With Native Property Retention

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Solution Overview

Problem

Existing crosslinking methods for glycosaminoglycans (GAGs) often compromise their native properties, leading to reduced effectiveness in medical and cosmetic applications, and there is a need for a method that maintains these properties while efficiently crosslinking GAGs.

Innovation Solution

Crosslinking GAG molecules using di-, tri-, tetra-, and oligosaccharides as spacer groups to form covalent bonds, minimizing the introduction of synthetic non-carbohydrate structures and maintaining native properties, with a process involving activation and crosslinking steps using peptide coupling reagents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional crosslinking methods are used for GAGs, then crosslinking efficiency is improved, but the native properties of GAGs are compromised

Engineering Contradiction:
Improvecrosslinking efficiencyVSAvoidnative properties of GAGs
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical parameters of the crosslinking process by using carbohydrate-based crosslinkers with specific functional groups (amines, carbazates, hydrazines) that react selectively with carboxylic acid groups on GAGs. This allows efficient crosslinking while maintaining the native properties of the GAGs because the crosslinkers are themselves carbohydrate-based and the reaction conditions are mild and specific.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite crosslinked structures where carbohydrate-based crosslinkers are integrated into the GAG network. The crosslinkers themselves are composed of carbohydrate units (such as glycosaminoglycan derivatives) that are covalently bonded to the GAG chains, forming a composite structure that maintains biocompatibility and native properties while achieving efficient crosslinking.

Inventive Principle:
Principle #40Composite materials

2Duration of action of stationary object

If crosslinking is performed to prolong duration of GAG polymers, then durability is improved, but the effectiveness in medical applications is reduced due to loss of native properties

Engineering Contradiction:
Improveduration of GAG polymersVSAvoideffectiveness in medical applications
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent modifies the crosslinking parameters by using specific carbohydrate-based crosslinkers with controlled reactivity. The crosslinkers contain functional groups that react selectively with carboxylic acid groups on GAGs under mild conditions, allowing the GAGs to be crosslinked sufficiently to prolong their duration in the body while preserving their native properties and effectiveness in medical applications.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces carbohydrate-based crosslinkers as intermediary molecules that mediate the crosslinking process. These crosslinkers act as bridges between GAG chains, forming stable covalent bonds that prolong the duration of the polymer network while their carbohydrate nature ensures they do not compromise the biocompatibility or effectiveness of the GAGs for medical use.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If synthetic crosslinkers are used, then crosslinking efficiency is improved, but immune response increases due to non-carbohydrate structures

Engineering Contradiction:
Improvecrosslinking efficiencyVSAvoidimmune response
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical composition parameter of the crosslinkers from synthetic non-carbohydrate structures to carbohydrate-based molecules. The crosslinkers are designed with carbohydrate units that have functional groups capable of reacting with GAG carboxylic acid groups. This parameter change eliminates the immune response issue because carbohydrate structures are naturally occurring in the body, while still maintaining efficient crosslinking capability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies homogeneity by using carbohydrate-based crosslinkers that are chemically compatible with the carbohydrate nature of GAGs. The crosslinkers share common structural features (carbohydrate units) with the GAGs they crosslink, creating a homogeneous molecular environment that reduces immune recognition and response, while the crosslinking functionality remains efficient through the carbohydrate-based chemical groups.

Inventive Principle:
Principle #33Homogeneity

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 method results in hydrogels with preserved native properties and minimal immune response, suitable for medical and cosmetic uses, particularly in soft tissue treatments and tissue engineering.

Implementation Method 1

the crosslinker comprises two or more functional groups capable of reacting with carboxylic acid groups on the GAG molecules to form stable covalent bonds

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentEP4279537B1Carbohydrate crosslinker
Publication Date: 2026.02.04 GALDERMA HLDG SA
  • EP4279537B1 patent drawing
  • EP4279537B1 patent drawing
  • EP4279537B1 patent drawing

AI summary

The invention relates to a hydrogel product comprising glycosaminoglycan molecules as the swellable polymer, wherein the glycosaminoglycan molecules are covalently crosslinked via crosslinks comprising a spacer group selected from the group consisting of di-, tri-, tetra-, and oligosaccharides.