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A high-stretch, high-viscosity, self-healing double-network hydrogel for tissue adhesion and its preparation method and application

A hydrogel and double network technology, applied in general culture methods, biochemical equipment and methods, applications, etc., can solve the problems of inability to achieve high strength, high toughness mechanical properties, inability to rebuild extracellular matrix, and low cell mass transfer efficiency and other issues, to achieve good cell compatibility, excellent tissue adhesion performance, and high self-healing efficiency

Active Publication Date: 2021-04-23
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most traditional hydrogels are composed of permanent covalent bonds or long-term stable strong physical bonds, and their mechanical characteristics are mainly elastic, so there are still many problems in tissue engineering applications: 1) Covalent bonds or long-term stable strong physical bonds The pore size of the cross-linked gel network is small, which makes the mass transfer efficiency of the cells inside the gel low and tends to apoptosis; 2) The chemically cross-linked hydrogel network area is rigid, so it can be used as a three-dimensional extracellular matrix for three-dimensional cell culture 3) Traditional hydrogels do not form adhesion to the contacting tissue / matrix surface due to the hydrophilic surface, so they are usually used to avoid Non-specific adsorption of macromolecules is used to avoid the adhesion of substances on its surface; 4) Traditional single-network hydrogels often have poor mechanical properties and cannot meet the requirements of higher mechanical properties such as high strength and high toughness
The existing commercial tissue adhesives for clinical application mainly realize the adhesion with tissues through chemical crosslinking and curing reactions, such as (CA, Dermabond, US)) (S.C. Woodward, J.B. Herrmann, J.L. Cameron, G. Brandes, E.J. Pulaski, F. Leonard, Annals of Surgery 1965, 162, 113.) and Succinimide ester (L.C. Sehl, O.M. Trollsas, D.G. Wallace, D .Toman, F.A.Delustro, J.A.Schroeder, G.H.Chu, Google Patents, 2004) and other tissue adhesive products, therefore all have the problem of cytotoxicity

Method used

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  • A high-stretch, high-viscosity, self-healing double-network hydrogel for tissue adhesion and its preparation method and application
  • A high-stretch, high-viscosity, self-healing double-network hydrogel for tissue adhesion and its preparation method and application
  • A high-stretch, high-viscosity, self-healing double-network hydrogel for tissue adhesion and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] In this example, polyethylene glycol diacrylate (PEGDA) was prepared by a one-step method. 35 g of polyethylene glycol (PEG) with a molecular weight of 35 kDa was dissolved in 80 mL of anhydrous dichloromethane, and 0.74 mL of triethylamine and 1 mL of acryloyl chloride was reacted at room temperature for 24 hours. After the reaction, the impurities were washed with anhydrous magnesium carbonate solution, extracted and separated, precipitated in ether, and then freeze-dried to obtain polyethylene glycol diacrylate with a molecular weight of 35 kDa. Carry out hydrogen NMR spectrum analysis to polyethylene glycol diacrylate ( figure 2 a) It can be seen that a double bond characteristic peak has appeared at 5.80ppm, and infrared spectroscopic analysis ( figure 2 b) at 1730cm -1 The peak corresponding to the C=O bond indicates the successful grafting of acrylate on the polyethylene glycol, and the unreacted polyethylene glycol content and the double bond peak area are d...

Embodiment 2

[0069] According to the data calculated in Example 1, polyethylene glycol with a molecular weight of 35 kDa is selected as the physical network, and 35 kDa is higher than the critical molecular weight of polyethylene glycol.

[0070] Dissolve 0.4 g of polyethylene glycol diacrylate with a molecular weight of 35 kDa and 0.4 g of polyethylene glycol with a molecular weight of 35 kDa in 1 mL of deionized water, and add 0.005 g of 2-hydroxy-4′-(2-hydroxyethoxy Base)-2-methylpropiophenone was mixed at 60° C. for 30 min to form a homogeneous solution to obtain a pre-polymerization solution (pre-polymerization liquid) of a double network hydrogel. Put the pre-polymerization solution at 365nm, 50mw / cm 2 The double network hydrogel was cross-linked under ultraviolet light for 30s, and its viscoelastic data, self-healing efficiency and lap bonding strength are listed in Table 3. Freeze the double-network hydrogel in the -80°C refrigerator for 1 hour and take it out. The cross-section o...

Embodiment 3

[0072] According to the data calculated in Example 1, polyethylene glycol with a molecular weight of 35 kDa is selected as the physical network, and 35 kDa is higher than the critical molecular weight of polyethylene glycol.

[0073] Dissolve 0.4 g of polyethylene glycol diacrylate with a molecular weight of 35 kDa in 1 mL of deionized water, and add 0.005 g of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone at 60 °C for 30 min to form a uniform solution to obtain a polyethylene glycol diacrylate hydrogel pre-polymerization solution (pre-polymerization solution). Put the pre-polymerization solution at 365nm, 50mW / cm 2 Crosslink under ultraviolet light for 30s to obtain polyethylene glycol diacrylate hydrogel. Dissolve 4 g of polyethylene glycol with a molecular weight of 35 kDa in 10 mL of aqueous solution to obtain a uniform polyethylene glycol solution. The acrylate hydrogel was soaked in polyethylene glycol solution for 24 hours until the polyethylene glycol molecules...

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Abstract

The present invention proposes a design strategy for a novel adhesive hydrogel material, and results in a highly stretchable, self-healing, and highly adhesive biocompatible hydrogel material. This type of material is based on the design principle of a double network structure. The first layer of covalently cross-linked network is composed of polymerizable polyethylene glycol-based polymers, and the second layer of non-covalent cross-linked network is formed by entanglement of ultra-high molecular weight hydrophilic polymers. Valence crosslink network. The grid size of the first network should be larger than the effective molecular size of the macromolecules constituting the second network, and the molecular weight of the polymers constituting the second network should be greater than its critical entanglement molecular weight, so that it can form effective molecular entanglement, Endows double network hydrogels with high stretchability, self-healing properties and high adhesiveness. This new type of adhesive hydrogel can quickly and repeatedly form stable bonds with the surface of various materials, and can quickly and repeatedly self-repair after being damaged by external forces. The material can be used as a cell culture carrier, a new type of suture-free dressing, and wearable sensor applications.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a high-stretch, high-viscosity, self-healing double-network hydrogel for tissue adhesion, a preparation method and application thereof. Background technique [0002] Hydrogel is a cross-linked hydrophilic polymer, which is composed of a porous gel network, rich in water, allowing the exchange of oxygen and nutrient metabolites, and has viscoelastic characteristics similar to human ECM, so it is widely used It can be used as a platform for studying three-dimensional cellular microenvironment and cell interaction, or as a substrate for constructing engineered tissues. However, most traditional hydrogels are composed of permanent covalent bonds or long-term stable strong physical bonds, and their mechanical characteristics are mainly elastic. There are still many problems in tissue engineering applications: 1) Covalent bonds or long-term stable strong physical bonds Th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/075C08L71/02A61L24/06A61L24/00A61K9/06A61K47/10A61K47/14C12N5/00
CPCA61K9/06A61K47/10A61K47/14A61L24/001A61L24/0031A61L24/0036A61L24/06A61L2400/06C08J3/075C08J2371/02C08J2471/02C12N5/0068C12N2533/30C08L71/02
Inventor 王华楠陈楷文
Owner DALIAN UNIV OF TECH
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