In-Situ Crosslinked Hydrogel via Dissolved Oxygen Oxidation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for preparing disulfide-bond crosslinked hydrogels are not suitable for industrialized production and clinical use due to the need for open-air conditions and the presence of residual crosslinking agents, which can cause toxicity and side effects.

Innovation Solution

A method for preparing injectable in-situ disulfide-bond crosslinked hydrogels by oxidizing thiol groups in a sealed container using dissolved oxygen, eliminating the need for open-air conditions and allowing for the regulation of oxygen concentration to control gelation properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If chemical crosslinking agents are used to prepare hydrogels, then crosslinking can be achieved, but residual crosslinking agents remain in the hydrogel causing toxicity and side effects

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidtoxicity from residual crosslinking agents
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent removes the harmful residual crosslinking agents from the system by using a different crosslinking mechanism. Instead of chemical crosslinking agents that leave residues, the invention uses disulfide bond formation through oxidation of thiol groups, which creates crosslinks without any residual harmful substances in the hydrogel.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of oxidation (which could be seen as a destructive process) into a beneficial crosslinking mechanism. By using controlled oxidation of thiol groups to form disulfide bonds, the invention achieves crosslinking without toxic residues, turning what could be a harmful process into a safe and effective crosslinking method.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

2Reliability

If disulfide-bond crosslinked hydrogels are prepared by open-air oxidation, then crosslinking can occur, but the process is not suitable for industrialized production and clinical use

Engineering Contradiction:
Improvecrosslinking completenessVSAvoidsuitability for industrialized production
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-forming thiolated polysaccharide derivatives before the crosslinking step. The polysaccharides are modified to contain thiol groups in advance, so that when the oxidation step occurs, the crosslinking can proceed efficiently and completely without requiring prolonged open-air exposure, thus making the process suitable for industrialization.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the oxidation parameters by using controlled oxidation conditions instead of prolonged open-air exposure. By adjusting oxidation time, oxygen concentration, and other parameters, the invention achieves complete crosslinking in a controlled manner that is compatible with industrialized production and clinical applications.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If thiol groups are oxidized to form disulfide bonds, then crosslinking is achieved, but the gelation process is slow and requires continuous oxygen consumption

Engineering Contradiction:
Improvecrosslinking efficiencyVSAvoidgelation speed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent uses strong oxidants to accelerate the oxidation of thiol groups to disulfide bonds. By employing potent oxidizing agents, the gelation process is significantly accelerated compared to natural oxidation, achieving rapid and efficient crosslinking without requiring continuous prolonged oxygen consumption.

Inventive Principle:
Principle #38Strong oxidants (Accelerated oxidation)

Solution Approach 2:

The patent ensures continuity of useful action by using oxidation mechanisms that proceed continuously and efficiently. The crosslinking process is designed to complete fully and rapidly without interruption, ensuring that gelation occurs quickly and completely without requiring continuous prolonged exposure to oxygen or other oxidizing conditions.

Inventive Principle:
Principle #20Continuity of useful action

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

This method enables the production of biocompatible, impurity-free hydrogels suitable for clinical use, facilitating large-scale industrial production and minimizing toxicity risks, with applications in wound healing and tissue regeneration.

Implementation Method 1

oxidizing the thiol groups into the disulfide bonds to form the crosslinked hydrogel by the oxygen dissolved in the crosslinkable active solution

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentEP2353612B1Injectable in-situ crosslinked hydrogel and the preparation method and use thereof
Publication Date: 2018.01.03 BIOREGEN BIOMEDICAL (CHANGZHOU) CO LTD
  • EP2353612B1 patent drawing

AI summary

The present invention discloses an injectable in-situ crosslinked hydrogel and its preparation method. The preparation method is as below: Filling the crosslinking active solution of at least one kind of the biocompatible macromolecules containing more than two thiol groups on the side chains into an injectable container and sealing it, and forming the in-situ disulfide-bond crosslinked hydrogel under the action of the dissolved oxygen; through controlling such parameters as partial pressure of oxygen gas, temperature and time, regulating concentration of the oxygen dissolved in the crosslinking active solution, and optimizing the gelation process and the gel properties. The present invention further relates to application of the injectable in-situ crosslinked hydrogel in pharmaceutics or surgery. The present invention has many advantages, such as no need for a crosslinking agent, simple preparation process, convenient application, containing no impurities, good biocompatibility, no toxic and side effect, and wide application in the medical science.