Hydrolysis-Resistant Hydrogels With Ester-Free Crosslinking
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Solution Overview
Problem
Existing hydrogels used in medical applications, such as SpaceOAR® and SpaceOAR Vue®, break down over time due to hydrolysis of ester linkages, limiting their long-term stability and applicability.
Innovation Solution
Development of hydrolysis-resistant hydrogels formed by crosslinking reactive multi-arm polymers with polyamino compounds, using cyclic-imidyl-oxycarbonyl-C2-C8-alkylene-carbonylamino-end groups and polyamino compounds, which do not contain ester groups, ensuring long-term stability in vivo.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If ester linkages are used in hydrogel crosslinks, then rapid crosslinking and clinical utility are achieved, but long-term stability deteriorates due to hydrolysis
Solution Approach 1:
The patent changes the chemical parameter of the crosslinkage type from ester bonds to amide bonds. This parameter change maintains the rapid crosslinking capability while fundamentally improving hydrolytic stability, as amide bonds are significantly more resistant to hydrolysis than ester bonds.
Solution Approach 2:
The patent creates a composite crosslinking system using multiple components: cyclic anhydride-modified polymer, polyamino compound, and N-hydroxysuccinimide. This composite approach enables both rapid crosslinking through the anhydride-polyamino reaction and long-term stability through the formation of amide bonds with hydrolysis resistance.
2Reliability
If hydrolysis-resistant crosslinks are used, then long-term stability is improved, but crosslinking complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-modifying the polymer with cyclic anhydride groups before the crosslinking step. This preliminary modification simplifies the overall process because the anhydride groups are already in place to react with the polyamino compound, eliminating the need for complex in-situ generation of reactive groups during crosslinking.
Solution Approach 2:
The patent uses N-hydroxysuccinimide as an intermediary in the crosslinking reaction. This intermediary facilitates the formation of amide bonds between the cyclic anhydride-modified polymer and the polyamino compound, enabling controlled and efficient crosslinking while maintaining simplicity in the overall process.
3Ease of manufacture
If radiopacity is added to hydrogel, then imaging capability is improved, but material composition complexity increases
Solution Approach 1:
The patent applies universality by incorporating iodinated aromatic groups into the polymer structure that serve multiple functions: they provide radiopacity for imaging capabilities and simultaneously maintain the chemical functionality for crosslinking. This multi-functionality eliminates the need for separate imaging agents, simplifying the overall material composition.
Solution Approach 2:
The patent merges the imaging function with the structural polymer component by integrating iodinated aromatic groups directly into the polymer backbone or side chains. This consolidation combines what would traditionally be separate materials (polymer matrix and contrast agent) into a single integrated material system.
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 new hydrogels exhibit long-term stability, maintaining integrity for over 5 years with minimal bioresorption, expanding their medical applications and providing radiopacity.
Implementation Method 1
the reactive multi-arm polymer and the polyamino compound react to form a crosslinked hydrogel
Implementation Method 2
hydrolysis-resistant hydrogels... The breakdown occurs primarily through the hydrolysis of the ester linkages in the glutarate groups
Data Source
AI summary
In some aspects, systems for forming hydrogels are provided that comprises (i) a reactive multi-arm polymer that comprises three or more polymer arms linked to a core region, at least three of the polymer arms comprising a reactive moiety comprising a cyclic-imidyl-oxycarbonyl- end group and (ii) a polyamino compound comprising at least two amino (—NH2) groups, wherein the reactive multi-arm polymer and the polyamino compound react to form crosslinked hydrogels that do not contain ester groups and have long-term stability in vivo. In other aspects, the present disclosure pertains to crosslinked hydrogels formed from such systems and methods of treatment using such systems.