Functionalized double-network hydrogel as well as preparation method and application thereof

A dual-network, hydrogel technology, applied in medical science, prosthesis, tissue regeneration, etc., can solve the problems of poor stability and tissue selection specificity, limited cell deposition and distribution, short biological half-life, etc., and achieves simple preparation process Convenience, good cell affinity, effect of good microstructure

Active Publication Date: 2021-04-13
PEKING UNIV SCHOOL OF STOMATOLOGY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although growth factors have a good induction effect on cells, problems such as short biological half-life, lack of long-acting effects, poor stability in vivo and poor tissue selection specificity have not been effectively resolved. These defects limit the clinical application of growth factors. Further applications in
[0005] The construction of traditional DN gels usually involves complex preparation steps, toxic initiators, and acrylamide starting materia

Method used

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  • Functionalized double-network hydrogel as well as preparation method and application thereof
  • Functionalized double-network hydrogel as well as preparation method and application thereof
  • Functionalized double-network hydrogel as well as preparation method and application thereof

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preparation example Construction

[0066] In the second aspect, the present invention provides a method for preparing a functionalized double network hydrogel, which can be used to prepare the functionalized double network hydrogel provided in the first aspect of the present invention, the preparation method includes the following step:

[0067] (1) Chitosan is mixed and reacted with KGN activated by EDC / NHS to obtain a chitosan-KGN compound;

[0068] (2) the chitosan-KGN compound that step (1) obtains and Tetra-PEG-NH 2 Prepared as a first precursor solution;

[0069] (3) Tetra-PEG-NHS is formulated into the second precursor solution;

[0070] (4) Mixing the first precursor solution and the second precursor solution and then standing still to form a gel to obtain a composite hydrogel, and then subjecting the composite hydrogel to activation treatment to obtain a functional double network hydrogel.

[0071] Step (1): Step (1) is the step of coupling KGN to chitosan (CHI) by chemical means to obtain a CHI-KGN...

Embodiment 1

[0096] Preparation of CHI-KGN compounds

[0097] A CHI-KGN compound is prepared by using carbodiimide chemistry to form a chemically connected amide bond between the KGN terminal carboxyl group and the CHI amine group.

[0098] The preparation method comprises the following steps:

[0099] Weigh KGN 120mg, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 726mg, N-hydroxysuccinimide (NHS) 434.8mg and dissolve in 20mL distilled water , adjust the pH value of the solution to 5.7, stir and react at 37° C. for 2 h, fully activate the carboxyl group of KGN, and obtain an activated KGN solution.

[0100] Weigh 3600 mg of chitosan and add it to the above-mentioned activated KGN solution, then add distilled water to make the total volume of the solution reach 150 mL, and stir and react at 37° C. for 24 h.

[0101] The reactant after the reaction was dialyzed in a dialysis bag with a molecular weight cut-off of 20 kD, and the distilled water was changed every 12 hours...

Embodiment 2

[0110] Preparation of CHI-KGN compounds

[0111] A CHI-KGN compound is prepared by using carbodiimide chemistry to form a chemically connected amide bond between the KGN terminal carboxyl group and the CHI amine group.

[0112] The preparation method comprises the following steps:

[0113] Weigh KGN 120mg, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 726mg, N-hydroxysuccinimide (NHS) 434.8mg and dissolve in 20mL distilled water , adjust the pH value of the solution to 5.7, stir and react at 37° C. for 2 h, fully activate the carboxyl group of KGN, and obtain an activated KGN solution.

[0114] Weigh 4800 mg of chitosan and add it to the above-mentioned activated KGN solution, then add distilled water to make the total volume of the solution reach 150 mL, and stir and react at 37° C. for 24 h.

[0115] The reactant after the reaction was dialyzed in a dialysis bag with a molecular weight cut-off of 20 kD, and the distilled water was changed every 12 hours...

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Abstract

The invention relates to functionalized double-network hydrogel as well as a preparation method and application thereof. The functionalized double-network hydrogel is formed by interpenetrating a chitosan cross-linked network and a four-arm polyethylene glycol cross-linked network, wherein the chitosan cross-linked network is formed by chitosan ions coupled with KGN through cross-linking; the four-arm polyethylene glycol cross-linked network is formed by carrying out chemical reaction on a first precursor and a second precursor, wherein the first precursor is Tetra-PEG-NH2, and the second precursor is Tetra-PEG-NHS. The functionalized DN hydrogel provided by the invention not only has good mechanical properties and cell affinity, but also provides mechanical support for bone regeneration; and KGN can be slowly released, and necessary bioactive factors are continuously provided for seed cell osteogenic differentiation. The preparation method is simple in preparation process, low in price and easy to obtain, the double-network hydrogel can be prepared through simple steps, and no toxic initiator needs to be used.

Description

technical field [0001] The invention relates to the technical field of new medical materials, in particular to a functionalized double network hydrogel and its preparation method and application. Background technique [0002] Bone defects caused by inflammation, tumors, trauma, etc. are common and frequently-occurring diseases in humans, which seriously affect the physiological functions, physical and mental health and quality of life of patients. At present, the commonly used methods for repairing bone defects clinically include allograft bone, autologous bone transplantation, bone lengthening, etc., but the effect is often poor due to problems such as immune rejection, infectious diseases, and limited sources. Using tissue engineering technology, it is an effective treatment to use bone tissue engineering materials constructed from seed cells and biological scaffolds for bone defect repair. [0003] In tissue engineering, a good scaffold material is not only a cell carrie...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08L71/02C08L5/08A61L27/52A61L27/50A61L27/54A61L27/20A61L27/18
CPCC08J3/075C08J3/24A61L27/52A61L27/50A61L27/54A61L27/20A61L27/18C08J2371/02C08J2471/02C08J2405/08A61L2430/02A61L2300/216A61L2300/412C08L5/08C08L71/02
Inventor 余婷婷王星韩冰柳大为张云帆张凌云
Owner PEKING UNIV SCHOOL OF STOMATOLOGY
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