Hydrogel Precursor Powder Enzyme Activation
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Solution Overview
Problem
Existing hydrogel precursor formulations require separate activation of cross-linking enzymes prior to gel formation, leading to complexities in reproducibility and stability of the final hydrogel properties.
Innovation Solution
A hydrogel precursor formulation in the form of an unreacted powder comprising an activating enzyme, a cross-linking enzyme, and structural compounds that can be activated in water with minimal conductivity and specific pH, allowing for controlled gel formation without premature cross-linking, thereby simplifying the production process and enhancing reproducibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If separate activation of cross-linking enzyme is performed prior to gel formation, then the cross-linking reaction can be controlled, but the process complexity increases and reproducibility decreases
Solution Approach 1:
The invention combines the cross-linking enzyme and activating enzyme into a single hydrogel precursor formulation. This merging eliminates the need for separate activation steps, reducing process complexity while maintaining reliable and reproducible hydrogel formation through the integrated enzyme system.
Solution Approach 2:
The cross-linking enzyme is pre-loaded into the hydrogel precursor formulation along with the activating enzyme. This preliminary preparation ensures that all necessary components are in place before gel formation, enabling consistent and reproducible results without requiring separate activation procedures.
2Reliability
If cross-linking enzyme is activated in advance, then gelation can be controlled, but stability of the formulation decreases due to premature gelation
Solution Approach 1:
The formulation uses an intermediary activating enzyme that remains dormant until the gelation process begins. This intermediary mechanism prevents premature activation of the cross-linking enzyme, maintaining formulation stability during storage while enabling controlled activation when needed.
Solution Approach 2:
The invention utilizes parameter changes in the form of pH or ionic strength adjustments to trigger enzyme activation at the appropriate time. This ensures the cross-linking enzyme remains stable during storage but becomes active when the desired gelation conditions are achieved, maintaining both stability and reliability.
3Ease of manufacture
If multiple components are weighed and mixed separately, then the formulation flexibility is maintained, but manufacturing errors increase
Solution Approach 1:
The invention merges multiple components including cross-linking enzyme, activating enzyme, and hydrogel precursors into a single pre-formulated product. This eliminates the need for separate weighing and mixing operations, reducing manufacturing errors while simplifying the ease of use for end applications.
Solution Approach 2:
The hydrogel precursor formulation is designed as a self-contained system that requires minimal handling. The formulation automatically provides the correct proportions of all components, eliminating the need for user intervention in weighing and mixing, thereby improving both ease of manufacture and manufacturing precision.
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 formulation ensures stable and reproducible hydrogel properties over extended manufacturing times, with activated factor XIII remaining stable for at least 24 hours, reducing errors in weighing and mixing and minimizing negative effects on embedded cells.
Implementation Method 1
The cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer, preferably in water with a conductivity of ≤5 μS/cm with or without a buffer
Implementation Method 2
the covalent cross-link is mediated by a cross-linking enzyme which catalyses the cross-linking reaction between functional groups
Implementation Method 3
Cross-linking enzymes known from the blood coagulation system belong e.g. to the class of transglutaminases which catalyse the formation of an isopeptide bond between a amine group such as a protein-/peptide-bound lysine and the acyl group of a protein-/peptide-bound glutamine
Data Source
AI summary
A hydrogel precursor formulation which is in the form of an unreacted powder. The formulation comprises an activating enzyme, preferably thrombin, a cross-linking enzyme, preferably a transglutaminase, and more preferably factor XIII transglutaminase. The cross-linking enzyme is activatable by the activating enzyme in water with or without a buffer, and at least one structural compound A. The structural compound is crosslinkable by a selective reaction mediated by the crosslinking enzyme to form a hydrogel, wherein the cross-linking enzyme is activated.


