Iodinated Hydrogel Crosslinking via SPAAC
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The incorporation of 2,3,5-triiiodobenzamide groups into hydrogels for medical applications complicates the synthesis process, increases product costs, and requires complex quality control measures, while also necessitating stabilization of crosslinkers in buffer solutions to prevent premature crosslinking.
Innovation Solution
The use of a system comprising a first multifunctional molecule with azide groups and a second multifunctional molecule with cyclic alkyne groups, where at least one of the molecules is a reactive multi-arm polymer and one comprises an iodinated core, allows for rapid and efficient hydrogel formation through strain-promoted alkyne-azide cycloaddition without the need for buffer solutions or catalysts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If 2,3,5-triiiodobenzamide groups are incorporated into hydrogels to provide radiopacity, then X-ray visibility is improved, but synthesis process complexity and product cost increase
Solution Approach 1:
The patent extracts the radiopacity function from the complex multi-step functionalized PEG approach and implements it through a simpler iodinated core structure. By separating the radiopaque iodine-containing component from the polymer backbone, the synthesis becomes more straightforward and cost-effective while maintaining the desired radiopacity.
Solution Approach 2:
The patent uses composite materials by combining an iodinated core (providing radiopacity) with polymer arms (providing hydrogel formation capability). This composite approach allows each component to be optimized independently, simplifying synthesis and reducing costs compared to fully functionalized PEG systems.
2Reliability
If multiple functionalization steps are used to add both TIB and SG groups to PEG, then radiopacity and crosslinking capability are achieved, but manufacturing complexity and quality control difficulty increase
Solution Approach 1:
The patent segments the functional requirements into separate components: the iodinated core provides radiopacity and structural integrity, while the polymer arms provide crosslinking functionality. This segmentation eliminates the need for multiple sequential functionalization steps on a single polymer chain, simplifying the synthesis process and quality control.
Solution Approach 2:
The iodinated core serves multiple functions simultaneously: it provides radiopacity through iodine atoms, acts as a structural anchor for polymer arms, and enables crosslinking through the polymer arm functionalities. This multi-functionality reduces the number of separate synthesis steps required.
3Stability of the object's composition
If trilysine crosslinker is stabilized in buffer solution with controlled pH, then premature crosslinking is prevented, but product complexity and quality control activities increase
Solution Approach 1:
The patent introduces a spacer arm as an intermediary between the polymer and crosslinker, allowing the crosslinker to be delivered in a stable, non-buffered form. The spacer provides temporal and spatial separation, enabling the crosslinker to remain stable during storage and delivery, then become reactive upon mixing at the target site, thereby reducing formulation complexity.
Solution Approach 2:
The patent performs preliminary stabilization of the crosslinker through molecular design (incorporating stable chemical structures and spacers) rather than requiring ongoing buffer stabilization. This preliminary structural stabilization eliminates the need for complex pH-controlled buffer formulations during storage and delivery.
4Speed
If succinimidyl glutarate groups are used for rapid crosslinking, then gel formation speed is improved, but synthesis complexity increases due to multiple functionalization steps
Solution Approach 1:
The patent applies local quality by concentrating the rapid crosslinking functionality specifically at the polymer arm termini where spacers are attached, while the iodinated core maintains structural integrity. This localized functionalization achieves rapid crosslinking without requiring complex multi-step functionalization of the entire polymer structure.
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 approach results in high X-ray visibility, improved in vivo persistence, good homogeneity, and rapid hydrogel formation, while simplifying the synthesis and quality control processes and reducing costs.
Implementation Method 1
allows for rapid and efficient hydrogel formation through strain-promoted alkyne-azide cycloaddition
Implementation Method 2
results in high X-ray visibility
Implementation Method 3
The breakdown occurs primarily through the hydrolysis of the ester linkages associated with the glutarate groups
Data Source
AI summary
In some aspects, the present disclosure pertains to systems for forming crosslinked reaction products that comprises (a) a first composition that comprises a first multifunctional molecule that comprises a plurality of first reactive moieties that comprise azide groups and (b) a second composition that comprises a second multifunctional molecule that comprises a plurality of second reactive moieties that comprise cyclic alkyne groups, where at least one of the first and second multifunctional molecules is a reactive multi-arm polymer and where at least one of the first and second multifunctional molecules comprises an iodinated core. Other aspects of the present disclosure include crosslinked networks formed from such first and second multifunctional molecules and methods of treatment based on crosslinked networks formed from such first and second multifunctional molecules.