Cross-linked Polyol Composition for Tissue Engineering
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Solution Overview
Problem
Existing crosslinking methods of carbohydrates with epoxides or epihalohydrins result in excessive pendant groups, raising toxicological concerns due to the incorporation of excessive crosslinker amounts, which is a challenge in tissue engineering applications.
Innovation Solution
A method involving the removal of water before initiating crosslinking, using a polyol crosslinked with multi-functional epoxides or epihalohydrins, specifically controlling the ratio of crosslinked hydroxide groups and ether groups to minimize pendant groups, thereby reducing toxicity and enhancing the composition's suitability for implantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crosslinking of carbohydrates with epoxides or epihalohydrins is performed using conventional methods, then crosslinking efficiency is achieved, but excessive pendant groups are formed causing toxicological concerns
Solution Approach 1:
The invention changes the chemical parameters of the crosslinking reaction by using specific crosslinking agents (epoxides or epihalohydrins) under controlled conditions to favor crosslink formation over pendant group formation. The patent specifies controlling the molar ratio, pH, and temperature to achieve high crosslinking efficiency while minimizing toxic pendant groups.
Solution Approach 2:
The invention introduces a catalyst as an intermediary substance to mediate the crosslinking reaction. The catalyst facilitates the formation of crosslinks between carbohydrate molecules while reducing the formation of pendant groups, thereby improving the reliability of crosslinking and reducing toxicity simultaneously.
2Reliability
If excessive crosslinker is incorporated to achieve effective crosslinks, then crosslinking efficiency improves, but toxicological concerns increase
Solution Approach 1:
The invention optimizes the concentration and molar ratio parameters of the crosslinking agent to achieve effective crosslinking with minimal excess. By precisely controlling these parameters, the patent achieves high crosslinking efficiency while keeping the amount of residual crosslinker (and thus toxicity) low.
Solution Approach 2:
The invention employs monitoring and control mechanisms to track the crosslinking reaction progress and adjust conditions in real-time. This feedback approach ensures that the reaction stops at the optimal point where sufficient crosslinks are formed without excessive crosslinker incorporation, thereby reducing toxicity.
3Ease of manufacture
If crosslinking is performed without water removal, then the process is simpler, but pendant group formation increases causing toxicity
Solution Approach 1:
The invention performs water removal as a preliminary action before initiating the crosslinking reaction. By removing water in advance, the reaction conditions are optimized to favor crosslink formation over pendant group formation, reducing toxicity while maintaining procedural simplicity through pre-prepared reaction conditions.
Solution Approach 2:
The invention uses a catalyst as an intermediary to facilitate the crosslinking reaction under anhydrous conditions. The catalyst enables efficient crosslinking without requiring excessive water removal steps, thus maintaining ease of manufacture while reducing pendant group formation and 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 approach significantly reduces pendant groups in favor of crosslinks, resulting in a composition with low residual toxicity, suitable for direct implantation and effective tissue engineering applications, while maintaining the necessary crosslinking efficiency for structural integrity.
Implementation Method 1
a polyol crosslinked with a multi-functional epoxide or an epihalohydrin or a molecule or crosslinker mixture comprising multiple epihalohydrin and/or epoxide groups
Data Source
AI summary
The composition comprises a polyol crosslinked with a) a multifunctional epoxide; or b) an epihalohydrin; or c) a molecule or crosslinker mixture comprising multiple epihalohydrin and/or epoxide groups or molecules. The composition has a number N1 of effective ether crosslinks per crosslinker molecule as calculated by subtracting 1 from the average number of distinct polyol repeat units bound per crosslinker molecule. The remaining reactive groups on the crosslinker are ineffective in crosslinking and provide a number N2 of pendant groups per crosslinker molecule. Among the N2 groups per crosslinker there are N3 groups per crosslinker that are unreacted or otherwise retain reactivity against nucleophiles. The relationship between N1 and N2 is: N1>0.35 (N1+N2).