Silylated Polysaccharide Hydrogel Crosslinking
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Solution Overview
Problem
Current polysaccharide hydrogels, particularly hyaluronic acid gels, face challenges in achieving desirable mechanical properties and biocompatibility due to high toxicity from conventional cross-linking agents, and existing modifications do not adequately reduce the amount of cross-linking agents used while maintaining injectability and stability.
Innovation Solution
A process combining a conventional cross-linking agent with molecules having a single reactive function that forms Si—O—Si bonds, reducing the amount of cross-linking agents like BDDE and enhancing biocompatibility, allowing for the creation of injectable hydrogels with improved cohesiveness and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If conventional cross-linking agents are used to achieve desirable mechanical properties and in vivo durability, then the gel strength and stability are improved, but the toxicity increases due to reactions with biopolymers such as peptides, carbohydrates and DNA
Solution Approach 1:
The patent uses silane molecules as intermediary agents that first functionalize the polysaccharide chains with Si-OR groups, which then undergo sol-gel condensation to form Si-O-Si crosslinks. This intermediary silane approach allows crosslinking without direct use of highly reactive conventional crosslinking agents, thereby reducing toxicity while maintaining gel strength.
Solution Approach 2:
The patent changes the chemical mechanism of crosslinking from direct conventional crosslinking agent reactions to sol-gel based Si-O-Si bond formation. This parameter change in the crosslinking mechanism allows achieving desirable mechanical properties while reducing the amounts of conventional crosslinking agents and their associated toxicity.
2Object-affected harmful factors
If the amount of cross-linking agent is reduced to improve biocompatibility, then the toxicity is reduced, but the gel cohesiveness and mechanical properties deteriorate
Solution Approach 1:
The patent creates a composite crosslinking system combining polysaccharide chains functionalized with silane groups and forming Si-O-Si bonds. This composite approach, integrating organic polysaccharide with inorganic silane crosslinks, achieves enhanced gel cohesiveness with reduced conventional crosslinking agent content, improving biocompatibility.
3Stability of the object's composition
If polysiloxane polymer diepoxide or APTES with TEOS and PDMS are used to form Si-O-Si crosslinks, then the gel stability is improved, but the mechanical properties become too strong for injection
Solution Approach 1:
The patent optimizes parameters including silane concentration, water content, pH, and temperature to control the sol-gel reaction kinetics. By carefully adjusting these parameters, the gel achieves sufficient stability while maintaining softer mechanical properties that enable injectability, unlike previously reported systems that were too rigid.
4Object-affected harmful factors
If the cross-linking reaction parameters are adjusted to reduce cross-linking agent amount, then the toxicity is reduced, but the gel mechanical properties and cohesiveness deteriorate
Solution Approach 1:
The patent substitutes conventional chemical crosslinking mechanisms with sol-gel based Si-O-Si bond formation. This mechanism substitution allows achieving desirable gel cohesiveness through controlled hydrolysis and condensation of silane groups, reducing dependence on conventional crosslinking agents and their toxicity.
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 combined approach results in hydrogels with enhanced mechanical properties, including cohesiveness and stability after sterilization, making them suitable for therapeutic, cosmetic, and aesthetic applications while minimizing toxicity and cross-linking agent usage.
Implementation Method 1
functionalization of the polysaccharide with at least a silane molecule... in which the silane molecule has at least one reactive function capable of reacting with a functional group of the polysaccharide
Implementation Method 2
at least a part of the Si-OR groups having undergone a sol-gel reaction... hydrolysis of the Si-OR groups
Implementation Method 3
the Si-OR groups having undergone a sol-gel reaction... condensation of the Si-OH groups to form Si-O-Si bonds
Data Source
AI summary
The present invention relates to a process for preparing a hydrogel, comprising the following steps: a) provision of a polysaccharide or a salt thereof; b) crosslinking of the polysaccharide in the presence of 0.05 to 10 mol %, preferentially 0.1 to 2 mol %, of at least one crosslinking agent, or a salt thereof, per 1 mol of repeat units of the polysaccharide; c) functionalisation of the polysaccharide with at least one silylated molecule of formula Chem. I or a salt thereof; d) sol-gel reaction of at least one part of the Si—OR10 groups and optionally at least one part of the SiOR4 groups of the molecule of formula Chem. I or a salt thereof when they are present.