Reactive Hydrogel Particles via Enzymolysis for Secondary Crosslinking
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Solution Overview
Problem
Existing methods for preparing hydrogel particles are complex, low in flux, and not suitable for large-scale production, resulting in hydrogel particles with low reactivity and limited customization options, which hinders their application in biomedicine.
Innovation Solution
A preparation method involving polymerization of double-bond modified polyethylene glycol, a modified natural polymer, and an optional active functional monomer, followed by enzymolysis to expose active groups on the hydrogel particle surface, enabling high reactivity and biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If traditional modification methods (micro-droplet self-assembly, layer-by-layer chemical assembly, chemical grafting) are used to prepare hydrogel particles, then the particles have good monodispersity and controllable properties, but the production flux is low and large-scale production is not feasible
Solution Approach 1:
The patent changes the preparation parameters by using a bulk polymerization method with controlled variables (monomer concentration, initiator amount, temperature, pH) to achieve both high productivity and good particle uniformity. The method transitions from drop-based assembly to bulk-based polymerization, fundamentally changing how particles are formed to enable scale-up while maintaining quality
Solution Approach 2:
The patent extracts and eliminates complex purification steps and surfactant-based processes from the traditional preparation methods. By using a direct bulk polymerization approach, the method removes unnecessary intermediate purification operations and avoids the need for surfactant removal, thereby simplifying the process and enabling large-scale production
2Manufacturing precision
If traditional methods are used to prepare hydrogel particles, then the particles can be obtained with controlled properties, but the production cost is extremely high due to surfactants and dispersed oil phases
Solution Approach 1:
The patent replaces expensive surfactants and oil phases with water as the continuous medium. The method uses inexpensive materials (water, monomers, initiators) and eliminates the need for costly surfactant systems and oil-based dispersions, thereby dramatically reducing production costs while maintaining particle quality
Solution Approach 2:
The patent extracts and removes surfactants and dispersed oil phases from the preparation process entirely. By using a water-based bulk polymerization method, the technique eliminates these expensive components and their associated purification requirements, achieving both cost reduction and process simplification
3Stability of the object's composition
If double cross-linked particle gel is prepared using water-in-oil emulsion dispersion method, then the particles have a double cross-linked structure, but the process is complex and cannot be used for large-scale production
Solution Approach 1:
The patent changes the fundamental parameters of the preparation method by using bulk polymerization instead of emulsion dispersion. This parameter change simplifies the process while maintaining the ability to create cross-linked structures through controlled polymerization conditions and functional group reactions
Solution Approach 2:
The patent replaces the mechanical emulsion dispersion process with a chemical polymerization process. Instead of using mechanical mixing and emulsion formation, the method uses chemical reactions (polymerization and crosslinking) to directly form the desired structure, thereby simplifying the process and enabling scale-up
4Adaptability or versatility
If branched macromolecule is grafted to thiolated hyaluronic acid, then the modified hyaluronic acid is obtained, but the reactivity is extremely low and cannot be used for subsequent secondary crosslinking
Solution Approach 1:
The patent changes the chemical parameters by using double-bond modified polyethylene glycol instead of branched macromolecules. This parameter change results in higher reactivity due to the presence of active double bonds that can participate in subsequent crosslinking reactions, while maintaining a relatively simple preparation process
Solution Approach 2:
The patent introduces local reactivity by incorporating double bonds at specific locations within the polyethylene glycol chains. These localized active sites (double bonds) provide high reactivity for subsequent crosslinking while the rest of the polymer structure maintains its functional properties, achieving both versatility and ease of manufacture
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 method allows for simple, low-cost large-scale production of highly reactive hydrogel particles with enhanced biocompatibility, facilitating cell culture, tissue engineering, and drug delivery applications.
Implementation Method 1
performing polymerization reaction of double-bond modified polyethylene glycol, a modified natural polymer and an optional active functional monomer to obtain a gel
Implementation Method 2
performing enzymolysis reaction of the gel particle and an enzyme to obtain the hydrogel particle with reactivity
Data Source
AI summary
The present disclose relates to a high-reactivity hydrogel particle and preparation method therefor and use thereof. The preparation method comprises the following steps: (1) performing polymerization reaction of double-bond modified polyethylene glycol, a modified natural polymer and an optional active functional monomer to obtain a gel; (2) smashing the gel to obtain a gel particle; and (3) performing enzymolysis reaction of the gel particle and an enzyme to obtain the hydrogel particle with reactivity. The double-bond modified polyethylene glycol has a double bond and a polyethylene glycol chain segment, the modified natural polymer has sulfydryl or a double bond, the active functional monomer is selected from a sulfydryl functionalized biological adhesive peptide or sulfydryl functionalized cholesterol, and the enzyme is an enzyme corresponding to the natural polymer. The obtained hydrogel particle has high reactivity and can be used for subsequent secondary crosslinking. The hydrogel particle also has good biocompatibility.