Collagen Silk Fibroin Composite Hydrogel Stiffness Control

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Solution Overview

Problem

Current hydrogels, particularly those made from collagen and silk fibroin, face limitations in stiffness range and biocompatibility, making them unsuitable for cell encapsulation and tissue engineering applications, as they either have low stiffness or are difficult to handle, especially for soft tissues like nerves.

Innovation Solution

A composite hydrogel is developed by mixing collagen with an α-helix structure and silk fibroin with a β-sheet structure, forming an interpenetrating network through hydrogen bonding, allowing for adjustable stiffness between 0.05 kPa to 40 kPa, suitable for various tissue types, and facilitating cell encapsulation and growth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If collagen hydrogels are used to provide soft mechanical properties suitable for soft tissues, then the stiffness is reduced to match soft tissue requirements, but the gelation becomes less controllable and the mechanical strength is insufficient

Engineering Contradiction:
ImprovestiffnessVSAvoidgelation control
Core Design Contradiction:
TemperatureVSEase of manufacture

Solution Approach 1:

The patent combines collagen with silk fibroin to create a composite hydrogel system. This composite approach allows the collagen component to provide soft tissue-appropriate stiffness while the silk fibroin component contributes to gelation control and mechanical strength, resolving the contradiction between achieving soft mechanical properties and maintaining manufacturability

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent utilizes temperature-dependent gelation characteristics of both collagen and silk fibroin. By controlling the temperature during gelation, the system achieves controllable gel formation while maintaining the desired soft stiffness properties suitable for soft tissue applications

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If silk fibroin concentration is increased to achieve higher mechanical strength and controllable gelation, then the gelation becomes more controllable and mechanical properties improve, but the stiffness becomes too high for soft tissue applications

Engineering Contradiction:
Improvegelation controlVSAvoidstiffness
Core Design Contradiction:
Ease of manufactureVSTemperature

Solution Approach 1:

By creating a composite of collagen and silk fibroin, the patent balances the high stiffness contribution from silk fibroin with the softening effect of collagen. This allows the system to maintain controllable gelation and adequate mechanical strength while achieving the lower stiffness required for soft tissue applications

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent optimizes the local composition ratios of collagen to silk fibroin to achieve different stiffness levels in different regions or formulations, allowing customization for specific soft tissue applications while maintaining overall gelation control

Inventive Principle:
Principle #3Local quality

3Strength

If chemical cross-linking is used to increase the stiffness of collagen hydrogels, then the mechanical strength is improved, but the biocompatibility is reduced and cell encapsulation becomes limited

Engineering Contradiction:
Improvemechanical strengthVSAvoidbiocompatibility
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent replaces chemical cross-linking mechanisms with physical cross-linking through hydrogen bonding between collagen and silk fibroin molecules. This substitution maintains the mechanical strength needed for tissue engineering while preserving biocompatibility and enabling cell encapsulation, as no toxic chemical cross-linking agents are required

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Object-affected harmful factors

If natural polymers are used to ensure biocompatibility and non-toxic decomposition, then the biocompatibility is improved, but the gelation control and mechanical property tuning become more difficult

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidgelation control
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent combines two natural polymers, collagen and silk fibroin, each with complementary properties. Collagen provides biocompatibility and cell adhesion sites, while silk fibroin contributes to gelation control and mechanical strength. This composite natural polymer system overcomes the limitations of individual natural polymers by enabling both biocompatibility and controllable gelation

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent utilizes the different gelation temperature characteristics of collagen and silk fibroin to achieve controlled gelation. By adjusting the temperature and concentration parameters, the system achieves precise control over gel formation while maintaining the biocompatibility inherent to natural polymers

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 composite hydrogel exhibits excellent mechanical properties, allowing for cell adhesion, proliferation, and resistance to cell traction forces, with adjustable stiffness suitable for a wide range of tissues, including soft and hard tissues, and demonstrates long-term viability and growth in both in vitro and in vivo settings.

Implementation Method 1

forming an interpenetrating network by molecular interaction between the collagen and silk fibroin proteins

Methodology Applied
Scientific EffectHydrogen bonding: Chemical Bonding

Implementation Method 2

a network is formed by molecular interaction between the collagen and silk fibroin proteins

Methodology Applied
Scientific EffectMolecular interaction: Van der Waals Force

Data Source

PatentEP3476409A1Composite hydrogel for cell encapsulation comprising collagen and silk fibroin, and preparation method thereof
Publication Date: 2019.05.01 DANKOOK UNIV CHEONAN CAMPUS IND ACADEMIC COOP FOUND
  • EP3476409A1 patent drawingFigure 1
  • EP3476409A1 patent drawingFigure 2a~2e
  • EP3476409A1 patent drawingFigure 3~4b

AI summary

The present invention relates to a method for preparing a composite hydrogel for cell encapsulation comprising collagen and silk fibroin, comprising forming a gel by mixing collagen having an α-helix structure and silk fibroin having a β-sheet structure; and to a composite hydrogel for cell encapsulation prepared accordingly. The composite hydrogel of the present invention exhibits stiffness in the range of 0.05 kPa to 40 kPa, which is suitable for most tissues; allows cell encapsulation; assists cell adhesion and proliferation; restrains shrinkage exerted by cell traction forces; and shows a beneficial effect for long-term in vitro cultures and in vivo tissue engineering.