In Vivo Crosslinked Embolic Hydrogel via Bioorthogonal Click Chemistry
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Solution Overview
Problem
Current embolization products, such as coils and plugs, face challenges in efficiently and completely embolizing both large and small blood vessels due to their delivery difficulties and inefficiencies in complex vascular structures.
Innovation Solution
A crosslinked embolic hydrogel is formed from a hydrophilic polymer functionalized with biorthogonally reactive groups and a crosslinking agent, which react selectively to form a gel only at specific concentrations, allowing for precise embolization in smaller vessels and complex targets, and can be applied using embolization coils or microbeads for enhanced delivery and retention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If coils are used for embolization, then delivery into large blood vessels is relatively easy, but embolization efficiency and completeness in large vessels is insufficient
Solution Approach 1:
The invention uses composite materials combining hydrophilic polymers with biorthogonally reactive groups and crosslinking agents to form hydrogels that can be delivered via coils while providing complete embolization. The composite structure allows the material to be delivered in a liquid state through existing coil systems, then crosslinks in situ to provide reliable, complete vessel occlusion.
Solution Approach 2:
The invention changes the physical state parameter of the embolic material from solid (traditional coils) to liquid/gel state, allowing delivery through catheters and coils, then transforms it in situ through biorthogonal click chemistry crosslinking to provide reliable embolization. This parameter change enables compatibility with existing delivery systems while achieving complete embolization.
2Reliability
If embolic plugs are used for large vessels, then embolization efficiency is improved, but delivery difficulty increases
Solution Approach 1:
The invention changes the physical state of the embolic material from solid plug form to liquid/gel form that can flow through catheters and around coils, enabling easy delivery to large vessels, then transforms it in situ through crosslinking to provide efficient embolization comparable to plugs.
Solution Approach 2:
The invention uses biorthogonally reactive groups as intermediaries that enable crosslinking between polymer chains in the presence of biological systems. These reactive groups act as mediators that allow the material to crosslink reliably in vivo without interfering with biological processes, achieving plug-like embolization efficiency with liquid deliverability.
3Reliability
If traditional embolization methods are used for smaller vessels or AVMs, then treatment is attempted, but embolization effectiveness is reduced due to small and complex target nature
Solution Approach 1:
The invention segments the embolic material into molecular components (polymers with biorthogonally reactive groups and crosslinking agents) that can flow independently through small vessels and complex vascular structures, then crosslinks in situ to provide effective embolization in small vessels and AVMs where traditional solid embolics cannot reach.
Solution Approach 2:
The invention changes the viscosity and flow properties of the embolic material by using liquid polymer solutions that can navigate small vessels and complex AVM architectures, then transforms to gel state through crosslinking to provide effective embolization in previously difficult-to-treat small vessels.
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 crosslinked hydrogel effectively blocks blood flow in targeted areas, providing a more efficient and precise embolization method with reduced porosity and improved delivery, suitable for both large and small blood vessels, including complex vascular malformations.
Implementation Method 1
the first and second reactive groups comprise biorthogonally reactive pairs that react to form the crosslinked embolic hydrogel
Implementation Method 2
the first and second reactive groups form a covalent bond when brought in contact with each other
Implementation Method 3
A crosslinked embolic hydrogel is formed from a hydrophilic polymer functionalized with biorthogonally reactive groups and a crosslinking agent
Data Source
AI summary
A crosslinked embolic hydrogel is disclosed, the crosslinked embolic hydrogel comprising a hydrophilic polymer functionalized with first reactive groups and a crosslinking agent functionalized with second reactive groups; wherein the first and second reacting groups comprise a biorthogonally reactive pair that react to form the crosslinked embolic hydrogel. Methods and systems are also disclosed.