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Self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, and preparation method and application of self-crosslinking hyaluronic acid and gelatin composite hydrogel injection

A hydrogel injection, hyaluronic acid technology, applied in pharmaceutical formulations, medical science, prostheses, etc., can solve the problems of complex preparation process, difficulty in maintaining various cell proliferation and biological functions, poor biocompatibility, etc. The effect of strong controllability, prevention of cell loss and easy operation

Pending Publication Date: 2020-09-08
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to address the above problems, to provide a self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, the preparation material is selected to biomime the polysaccharide and protein components in the natural extracellular matrix, and the biomimetic protein in the cross-linking mode The connection of disulfide bonds solves the problems in the prior art that traditional hydrogels need exogenous triggers, poor biocompatibility, complicated preparation process, and difficulty in maintaining various cell proliferation and biological functions.

Method used

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  • Self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, and preparation method and application of self-crosslinking hyaluronic acid and gelatin composite hydrogel injection
  • Self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, and preparation method and application of self-crosslinking hyaluronic acid and gelatin composite hydrogel injection
  • Self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, and preparation method and application of self-crosslinking hyaluronic acid and gelatin composite hydrogel injection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] This example discloses a preparation method of mercaptolated hyaluronic acid, and the specific steps are as follows:

[0060] (1) Dissolve sodium hyaluronate with a molecular weight of 340KDa in deionized water, add N-hydroxysuccinimide (NHS), fully dissolve, and then add 1-ethyl-(3-dimethylaminopropyl) Carbodiimide hydrochloride (EDC·HCl), fully dissolved, use 0.1mol / L and 1mol / L NaOH solution and 0.1mol / L and 1mol / L HCl solution to adjust the pH value of the mixture to 4.75~ 5.5, react at room temperature for 1-2 hours, then add cysteamine hydrochloride, and react at low temperature for 24 hours.

[0061] In this step, sodium hyaluronate, N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) and half The molar ratio of cystamine hydrochloride is 1:1:3:3.

[0062] (2) The reaction solution obtained in step (1) was dialyzed for 5 days in a hydrochloric acid solution with a pH value of 3.3 to 3.5, and then freeze-dried to obta...

Embodiment 2

[0066] This embodiment discloses the preparation method of thiolated gelatin, and the specific steps are as follows:

[0067] (1) Dissolve gelatin in deionized water at 60°C, add N-hydroxysuccinimide (NHS) after cooling to room temperature, fully dissolve, then add 1-ethyl-(3-dimethylaminopropyl) Carbodiimide hydrochloride (EDC·HCl), fully dissolved, use 0.1mol / L and 1mol / L NaOH solution and 0.1mol / L and 1mol / L HCl solution to adjust the pH value of the mixture to about 5.0 , react at room temperature for 1.5h, then add cysteamine hydrochloride, react at room temperature for 20h.

[0068] In this step, gelatin, N-hydroxysuccinimide (NHS), 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl), cysteamine salt The mass ratio of acid salt is 0.5:2:4:1.

[0069] (2) The reaction solution obtained in step (1) was dialyzed for 5 days in a hydrochloric acid solution with a pH value of 3.3 to 3.5, and then freeze-dried to obtain mercaptolated gelatin (GelSH). The merc...

Embodiment 3

[0072] In this example, the self-crosslinked hyaluronic acid and gelatin composite hydrogel injection was prepared, and the steps were as follows:

[0073] (1) Fully dissolve the thiolated hyaluronic acid and thiolated gelatin obtained by dialysis and freeze-drying with deionized water to a concentration of 6.0 wt%, wherein the mass ratio of thiolated hyaluronic acid to thiolated gelatin is 1:1.

[0074] (2) At room temperature, use 0.1mol / L and 1mol / L NaoH and 0.1mol / L and 1mol / L HCl solutions to adjust the pH value of the mixed solution to 7.5, immediately draw the mixed solution with a syringe, and quickly inject it into the mold, Gel at room temperature.

[0075] attached Figure 4 A macroscopic view of the hydrogel.

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Abstract

The invention belongs to the technical field of biological materials, and particularly relates to a self-crosslinking hyaluronic acid and gelatin composite hydrogel injection, and a preparation methodand application of the self-crosslinking hyaluronic acid and gelatin composite hydrogel injection. The structure of the self-crosslinking hyaluronic acid and gelatin composite hydrogel injection is shown as a formula I. According to the preparation method, the two sulfydryl modified natural materials are prepared through a spontaneous oxidation reaction for forming disulfide bonds. The self-crosslinking hyaluronic acid and gelatin composite hydrogel injection provided by the invention can be used as a tissue engineering scaffold or / and other biological material loaded cells, drugs and bioactive substances. The preparation method is scientific in design and is simple and convenient to operate, and the prepared hydrogel injection has good hydrophilicity, biocompatibility and degradability,can well support normal form and proliferation behaviors of cells and promote anabolism of the cells, and shows an application prospect in tissue engineering and regenerative medicine.

Description

technical field [0001] The invention belongs to the technical field of biomaterials, in particular to a self-crosslinking hyaluronic acid and gelatin composite hydrogel injection and a preparation method and application thereof. The injection can be used in tissue engineering and regenerative medicine, and has good application prospects in tissue regeneration, wound repair and the like. Background technique [0002] Since the concept of tissue engineering was proposed, researchers have widely applied it in many fields of biomedicine, not only constructing various engineered tissues and organs in animal models, but also applying it clinically and achieved certain results. [0003] Compared with traditional organ transplantation, tissue engineering technology has no or less immune rejection, avoids shortage of donor sources and ethical issues, and is expected to achieve tissue and organ reconstruction, thereby solving clinical problems. In tissue engineering, there are three...

Claims

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Application Information

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IPC IPC(8): A61L27/38A61L27/48A61L27/50A61L27/52A61L27/58C08J3/24C08J3/075C08L5/08C08L89/00
CPCA61L27/3817A61L27/3852A61L27/3895A61L27/48A61L27/50A61L27/52A61L27/58A61L2400/06A61L2430/06C08J3/075C08J3/246C08J2305/08C08J2389/00C08L5/08C08L89/00
Inventor 樊渝江王玉祥孙勇张兴栋
Owner SICHUAN UNIV
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