Crosslinkable Functionalized Gelatin for Low Pyrogenic Hydrogels
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Solution Overview
Problem
Gelatin-based hydrogels for biomedical applications face challenges due to high endotoxin and pyrogen content, contamination from microbial components, and inefficient purification processes, which can lead to immune responses and microbial contamination risks.
Innovation Solution
Development of carboxylic acid-functionalized gelatin with low pyrogen content, specifically low endotoxin levels, achieved through a process involving modification with N-hydroxysuccinimide esters, pH adjustment, micelle-forming surfactants, and adsorbents like activated carbon to remove contaminants without the need for lengthy dialysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If traditional gelatin purification methods (dialysis) are used, then pyrogen and endotoxin removal is achieved, but the process requires lengthy dialysis time and complex procedures
Solution Approach 1:
The patent extracts harmful pyrogens and endotoxins from gelatin using specific binding agents (such as polymyxin B for endotoxins and other pyrogen-binding materials) that selectively bind and remove these contaminants through filtration or centrifugation, replacing the time-consuming dialysis process with a rapid extraction method that achieves comparable or superior purification in minutes rather than hours
Solution Approach 2:
The patent introduces intermediary substances (binding agents like polymyxin B, gelatinases, or other pyrogen-specific binders) that mediate the removal of endotoxins and pyrogens from gelatin. These intermediaries selectively bind to the harmful contaminants, allowing their efficient separation and removal through simple filtration or centrifugation, thereby achieving rapid purification without lengthy dialysis
2Adaptability or versatility
If gelatin is functionalized with crosslinkable groups, then crosslinking control and hydrogel design flexibility are improved, but pyrogenic activity and immune response risk increase
Solution Approach 1:
The patent applies preliminary purification actions before functionalization by pre-treating gelatin with binding agents to remove pyrogens and endotoxins, then proceeding with functionalization on the pre-purified gelatin. This sequence ensures that the functionalized gelatin maintains low pyrogenic activity while gaining the desired crosslinking capabilities and design flexibility
Solution Approach 2:
The patent changes the purity parameters of gelatin through chemical treatment with binding agents that specifically target and remove pyrogenic components. By adjusting the treatment conditions (such as pH, temperature, and binding agent concentration), the patent achieves optimal removal of harmful factors while preserving the gelatin's functional groups needed for crosslinking and hydrogel formation
3Ease of manufacture
If carbodiimide-mediated coupling is used for gelatin modification, then functional group attachment is achieved, but contamination from reagents and side products increases
Solution Approach 1:
The patent extracts unwanted reagent residues and side products from the functionalized gelatin using purification steps that involve binding agents or filtration methods. This removal process eliminates contamination from carbodiimide reagents and other modifiers, yielding a cleaner final product while maintaining the efficiency benefits of chemical functionalization
Solution Approach 2:
The patent employs purification strategies that discard harmful reagent contaminants while recovering and retaining the desired functional groups on gelatin. By using selective binding agents or filtration methods, the patent separates the useful functionalized gelatin from unwanted reagent residues, achieving both efficient manufacturing and product purity
Data Source
AI summary
The invention relates to a Gelatin functionalised via an amide bond with a substituted cross-linkable carboxylic acid moiety R—(CH2)n—COOH wherein n is an integer form 1 to 10 and further having a lipopolysaccharide content of less than 100 EU/g as well as a method for its preparation using an N-hydroxysuccinimide ester of the substituted cross-linkable carboxylic acid.