Double-Crosslinked Collagen Hydrogel for Strength and Biocompatibility

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Solution Overview

Problem

Existing collagen-based hydrogel materials face challenges in achieving mechanical robustness, elasticity, and biocompatibility while maintaining seamless integration with tissues, often leading to issues like degradation and immune response.

Innovation Solution

A method involving a collagen solution crosslinked with non-polymeric short-range carbodiimide and riboflavin under UV-A light, reinforced with cellulose nanofibers, forming a double-crosslinked hydrogel material that is chemically and physically stable, transparent, and biocompatible.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If chemical crosslinking techniques are used to enhance mechanical properties of collagen hydrogel, then mechanical strength is improved, but the material becomes either too soft or too brittle and loses biocompatibility

Engineering Contradiction:
Improvemechanical strengthVSAvoidbiocompatibility
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent employs dual crosslinking mechanisms: chemical crosslinking via carbodiimide to form stable covalent bonds for mechanical strength, and physical crosslinking via riboflavin-UVA photopolymerization to create a three-dimensional network that maintains elasticity and biocompatibility. This combination of chemical and physical crosslinking parameters resolves the contradiction by achieving both strength and flexibility simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite hydrogel system combining collagen with crosslinking agents (carbodiimide and riboflavin) to achieve synergistic properties. The collagen provides the structural framework and biocompatibility, while the crosslinking agents enhance mechanical properties without compromising the biological functionality, thus resolving the strength-biocompatibility trade-off

Inventive Principle:
Principle #40Composite materials

2Reliability

If extracted collagen is used in hydrogel form, then biocompatibility is improved, but mechanical toughness and elasticity are lost due to degradation

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical toughness
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The patent applies crosslinking treatments to collagen before implantation to pre-establish a stable three-dimensional network structure. This preliminary crosslinking action prevents degradation and maintains mechanical properties in the physiological environment, resolving the contradiction between biocompatibility and mechanical toughness

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent transforms the physical and chemical parameters of collagen through dual crosslinking, converting it from a degraded, weak state to a stabilized, mechanically robust state while preserving its biocompatible nature. The crosslinking density and network structure are optimized to balance mechanical strength and biological functionality

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 resulting hydrogel material is mechanically robust, elastic, and biocompatible, supporting tissue structure and facilitating seamless integration without rejection, with enhanced mechanical properties and transparency.

Implementation Method 1

The solution is allowed to react, forming an intermediate hydrogel material. The intermediate hydrogel material is exposed to ultraviolet A light, thereby forming an implantable hydrogel material

Methodology Applied
Scientific EffectPhotodynamic crosslinking: Photo-oxidation

Implementation Method 2

riboflavin to a concentration of 0.1 to 10 wt.%. Thereafter the formed intermediate hydrogel material is exposed to ultraviolet A light

Methodology Applied
Scientific EffectSinglet oxygen generation: Photosynthesis

Implementation Method 3

a non-polymeric short-range carbodiimide crosslinking agent to a concentration of 1-30 wt.%

Methodology Applied
Scientific EffectChemical crosslinking: Chemical Bonding

Data Source

PatentEP4440635B1Method of providing an implantable hydrogel material and an implantable hydrogel material
Publication Date: 2026.03.11 RAFAT MEHRDAD
  • EP4440635B1 patent drawingFigure 1~2
  • EP4440635B1 patent drawingFigure 3~4
  • EP4440635B1 patent drawingFigure 5~6b

AI summary

An implantable collagen-based hydrogel material is produced by providing a solution having a collagen molecule concentration of 0.1 to 30 wt.% and a cellulose nanofiber concentration of 0 to 30 wt.%. To the solution is added a non-polymeric short-range carbodiimide crosslinking agent at a concentration of 1-30 wt.%, and riboflavin at a concentration of 0.1 to 10 wt.%. The solution is allowed to react, forming an intermediate hydrogel material, and thereafter the intermediate hydrogel material is exposed to ultraviolet A light, forming an implantable hydrogel material.