Collagen Hyaluronic Acid Microgel Without Chemical Crosslinking

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Solution Overview

Problem

Current research on beta-glucan-based hydrogels is in its early stages, and there is a need for an optimal composition of collagen and hyaluronic acid for preparing microgels without chemical crosslinking agents, which is essential for effective tissue engineering and drug delivery applications.

Innovation Solution

A microgel composition comprising 7.5% to 20% (w/v) collagen and 1% to 5% (w/v) hyaluronic acid is developed, forming an electrostatic collagen-hyaluronic acid complex, which is then broken down to create a dispersion that undergoes natural sedimentation, eliminating the need for chemical crosslinking agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If chemical crosslinking agents are used to prepare microgels, then mechanical stability and structural integrity are improved, but biocompatibility and safety are worsened due to residual toxic chemicals

Engineering Contradiction:

Improvemechanical stabilityVSAvoidtoxicity from chemical crosslinking agents

Core Design Contradiction:

StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent replaces chemical crosslinking mechanisms with physical crosslinking through electrostatic interactions between collagen and hyaluronic acid. The oppositely charged polymers form stable complexes through ionic bonds, creating mechanically stable microgels without requiring toxic chemical crosslinking agents, thus resolving the contradiction between mechanical stability and biocompatibility

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces electrostatic interactions as an intermediary mechanism between collagen and hyaluronic acid molecules. These physical interactions serve as a mediator to achieve crosslinking and structural stability without direct chemical bonding, eliminating the need for harmful chemical crosslinking agents while maintaining mechanical integrity

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If hydrogel composition is optimized for tissue engineering, then biocompatibility is improved, but mechanical strength and shape stability are worsened

Engineering Contradiction:

ImprovebiocompatibilityVSAvoidshape stability

Core Design Contradiction:

ReliabilityVSStrength

Solution Approach 1:

The patent creates a composite hydrogel system combining collagen and hyaluronic acid in specific ratios (7.5-20% collagen and 1-5% hyaluronic acid). This composite structure leverages the complementary properties of both biopolymers: collagen provides structural framework and mechanical strength, while hyaluronic acid enhances biocompatibility and hydrophilicity, achieving both biocompatibility and shape stability simultaneously

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent optimizes the concentration parameters of collagen and hyaluronic acid within specific ranges to achieve the desired balance between biocompatibility and mechanical properties. By adjusting these compositional parameters, the microgel formulation achieves adequate shape stability while maintaining high biocompatibility for tissue engineering applications

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If microgel size and shape are varied for different applications, then versatility is improved, but manufacturing precision and consistency are worsened

Engineering Contradiction:

Improveapplication rangeVSAvoidsize consistency

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent employs a dynamic preparation process where microgels are formed through controlled aggregation and sedimentation of collagen-hyaluronic acid complexes. The process allows for controlled variation in microgel size and shape through adjustable parameters such as mixing conditions, concentration ratios, and sedimentation time, enabling versatility while maintaining adequate manufacturing consistency through standardized protocols

Inventive Principle:

Principle #15Dynamics

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 microgel composition provides a biocompatible, three-dimensional scaffold for tissue engineering with enhanced mechanical stability and prolonged persistence, suitable for cell cultivation and drug delivery, without the use of chemical crosslinking agents.

Implementation Method 1

forming electrostatic collagen-hyaluronic acid complex by mixing 7.5% (w/v) to 20% (w/v) of collagen with 1% (w/v) to 5% (w/v) of hyaluronic acid

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

subjecting the dispersion of the microgel to natural sedimentation

Methodology Applied

Scientific EffectSedimentation: Sedimentation

Data Source

PatentUS12005152B2Microgel composition comprising collagen and method of preparing the same

Publication Date: 2024.06.11 KOREA INST OF SCI & TECH

AI summary

The present disclosure relates to a microgel composition comprising collagen and hyaluronic acid and a method of preparing the same. The microgel according to an embodiment is composed of natural biocompatible substances and is non-toxic and has high mechanical stability or long persistence, and thus can be effectively used in a microgel composition, a three-dimensional scaffold composition, and a tissue-engineering scaffold.