Dual-network poly(N-acryloyl-L-alpha-amino acid)/hyaluronic acid composite hydrogel and preparation method thereof

A composite hydrogel and acryloyl technology, applied in the field of biomedical materials, can solve the problems of few applications, hydrogel brittleness and large modulus, and achieve the effect of simple process, good mechanical properties, and rapid reduction of dissociation properties

Active Publication Date: 2015-09-16
BEIJING ABACE BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the other hand, poly(N-acryloyl-L-α-amino acid) formed by radical polymerization of L-α-amino acid acryloyl derivatives also has many properties of polyamino acids, and has good applications in the field of biomedicine. However, the application of this kind of materia

Method used

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  • Dual-network poly(N-acryloyl-L-alpha-amino acid)/hyaluronic acid composite hydrogel and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0028] 1) Preparation of Hydrazide Hyaluronic Acid

[0029] Carbodiimide method is used to graft 2,2'-dithiodiacetylhydrazide on hyaluronic acid with a molecular weight of 1 million to obtain hydrazide hyaluronic acid with a substitution degree of 40%. The details are as follows: mix hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride with N-hydroxysuccinimide, 2,2'-dithiodiacetyl Hydrazine was dissolved in distilled water to prepare a hyaluronic acid solution with a concentration of 1%. The pH value of the system was adjusted to 5 with 1mol / L hydrochloric acid, and the reaction was stirred at room temperature for 48 hours. After the reaction, the reaction system was dialyzed with deionized water for 2 days ( The molecular weight cut-off of the dialysis bag is 3500Da, the same below) and freeze-dried at minus 20°C for 72 hours to obtain hydrazide hyaluronic acid. Among them, the number of repeating units of hyaluronic acid, 1-(3-dimethylaminopropyl)-3...

Embodiment 2

[0040] 1) Preparation of Hydrazide Hyaluronic Acid

[0041] Carbodiimide method is used to graft 2,2'-dithiodiacetylhydrazide on hyaluronic acid with a molecular weight of 2 million to obtain hydrazide hyaluronic acid with a substitution degree of 30%. The details are as follows: mix hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride with N-hydroxysuccinimide, 2,2'-dithiodiacetyl Hydrazine was dissolved in distilled water to prepare a hyaluronic acid solution with a concentration of 0.5%. The pH value of the system was adjusted to 5.5 with 1mol / L hydrochloric acid, and the reaction was stirred at room temperature for 24 hours. Dialyzed with distilled water for 2 days with a molecular weight cut-off of 3500Da, the Freeze drying at minus 20°C for 72 hours to obtain hydrazide hyaluronic acid. Among them, the number of repeating units of hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide, 2,2'-dithiobis Th...

Embodiment 3

[0051] 1) Preparation of Hydrazide Hyaluronic Acid

[0052] Using the carbodiimide method, 3,3'-dithiodipropionyl hydrazide was grafted onto hyaluronic acid with a molecular weight of 800,000 to obtain hydrazide hyaluronic acid with a substitution degree of 30%. The details are as follows: mix hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride with N-hydroxysuccinimide, 3,3'-dithiodipropyl Hydrazide was dissolved in distilled water to prepare a hyaluronic acid solution with a concentration of 0.8%. The pH value of the system was adjusted to 5 with 1mol / L hydrochloric acid. The reaction was stirred at room temperature for 24 hours, and the distilled water was dialyzed for 2 hours with a dialysis bag with a molecular weight cut-off of 3500Da. Two days later, it was freeze-dried at minus 20°C for 72 hours to obtain hydrazidated hyaluronic acid. Among them, the number of repeating units of hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hy...

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Abstract

The invention discloses dual-network poly(N-acryloyl-L-alpha-amino acid)/hyaluronic acid composite hydrogel and a preparation method thereof. Hydrazide hyaluronic acid and N-acryloyl-L-alpha-amino acid are used as main raw materials and are radiated by ultraviolet after being uniformly mixed with a crosslinking agent, and hydrazone bond crosslinking and photochemical crosslinking are realized to form the dual-network poly(N-acryloyl-L-alpha-amino acid)/hyaluronic acid composite hydrogel containing disulfide bonds in a crosslinking network chain. The disulfide bond in the hydrogel can be broken by responding to a reducing substance, so that the rapid dissociation of the hydrogel can be realized. The method has advantages of easiness in obtaining of raw materials, moderate reaction conditions, simple and rapid process and the like. The prepared hydrogel has characteristics of adjustability in strength, degradation speed, microhole structure, charge state and the like and is good in biological compatibility and cell adhesion property and wide in application prospect on the aspects of tissue engineering, three-dimensional cell culture, in-vitro tumor models and the like.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a double network poly(N-acryloyl-L-α-amino acid) / hyaluronic acid composite hydrogel and a preparation method thereof. Background technique [0002] With the rapid development of three-dimensional cell culture technology, hydrogel has attracted more and more attention, because it not only has a porous elastic hydration network similar to living tissue, but also facilitates the transport of oxygen, nutrients and metabolic waste in it, which can be used for cells. Adhesion, proliferation, and differentiation provide an ideal three-dimensional microenvironment. Hydrogels have been widely used in biomedical research fields, such as drug or protein delivery, cell delivery, bioadhesives, tissue engineering, three-dimensional cell culture in vitro, etc. Among them, hydrogels prepared from natural polymers, such as alginate, hyaluronic acid, chitosan, collagen, s...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L77/04
Inventor 钱军民崔宁胥伟军赵娜张雅萍
Owner BEIJING ABACE BIOTECH
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