HA-Alg Hydrogel via Schiff Base Crosslinking for Bioprinting

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Solution Overview

Problem

Conventional hydrogels face issues such as prolonged gelation time, cytotoxicity, and lack of shear-thinning properties, making them unsuitable for regenerative tissue engineering and bioprinting applications.

Innovation Solution

A method of preparing Hyaluronic acid-Alginate (HA-Alg) hydrogels by dissolving amine-hyaluronic acid and aldehyde-alginate in buffer solutions and mixing them in specific ratios to form a crosslinked hydrogel, which is non-toxic and exhibits shear-thinning properties, enabling efficient cell encapsulation and bioprinting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If conventional hydrogels are used, then they provide basic hydrogel properties, but they exhibit prolonged gelation time which decreases usability

Engineering Contradiction:
Improvegelation timeVSAvoidusability
Core Design Contradiction:
Loss of timeVSProductivity

Solution Approach 1:

The patent changes the chemical parameters of the hydrogel system by using amine-modified hyaluronic acid and aldehyde-modified alginate, which enables rapid gelation through Schiff base formation. This chemical modification approach transforms the gelation process from slow physical crosslinking to fast chemical crosslinking, reducing gelation time from hours to minutes while maintaining usability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite hydrogel system combining two different polymer components (amine-HA and aldehyde-alginate) that work synergistically. The composite nature allows the system to achieve fast gelation through complementary chemical reactions while maintaining the desirable properties of both parent polymers, thus improving both speed and usability

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If conventional hydrogels are used, then they provide structural support, but they exhibit cytotoxicity due to additives which limits cell encapsulation

Engineering Contradiction:
ImprovecytotoxicityVSAvoidcell encapsulation capability
Core Design Contradiction:
Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent extracts and eliminates harmful additives from the hydrogel system by using purely natural polymer components (hyaluronic acid and alginate) that crosslink through their inherent functional groups. This removal of synthetic additives and crosslinking agents eliminates cytotoxicity while preserving the ability to encapsulate cells, thereby improving both safety and versatility for biological applications

Inventive Principle:
Principle #2Taking out (Extraction)

3Object-affected harmful factors

If conventional hydrogels are used, then they maintain structural integrity, but they lack shear-thinning properties which reduces printability

Engineering Contradiction:
ImproveprintabilityVSAvoidshear-thinning properties
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent introduces dynamic rheological properties to the hydrogel by designing a system that exhibits shear-thinning behavior. The amine-HA/aldehyde-alginate crosslinked network allows the material to become less viscous under shear stress (during printing) and recover its structure afterward, providing both printability and structural stability through time-dependent and stress-dependent behavior

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 HA-Alg hydrogel achieves fast gelation, supports cell viability, and demonstrates enhanced mechanical strength and stability, making it suitable for encapsulating cells and macromolecules, and facilitating effective printing and chondrogenic differentiation.

Implementation Method 1

enabling cross-linking of the HA-NH2 and the Alg-CHO to form the HA-Alg hydrogel

Methodology Applied
Scientific EffectChemical crosslinking: Chemical Bonding

Implementation Method 2

demonstrates enhanced mechanical strength and stability, making it suitable for encapsulating cells and macromolecules, and facilitating effective printing

Methodology Applied
Scientific EffectShear-thinning: Shear Thinning

Data Source

PatentUS20250002659A1Method of preparing hyaluronic acid-alginate (ha-alg) hydrogel and ha-alg hydrogel
Publication Date: 2025.01.02 YODMUANG SUPANSA
  • US20250002659A1 patent drawing
  • US20250002659A1 patent drawing
  • US20250002659A1 patent drawing

AI summary

Disclosed is a method of preparing a Hyaluronic acid-Alginate (HA-Alg) hydrogel, the method comprising: dissolving a required amount of amine-hyaluronic acid (HA-NH2) in a first buffer solution to form an HA-NH2 solution of a first predefined concentration; dissolving a required amount of aldehyde-alginate (Alg-CHO) in a second buffer solution to form an Alg-CHO solution of a second predefined concentration; and mixing the HA-NH2 solution and the Alg-CHO solution in a predefined ratio for preparing the HA-Alg hydrogel.