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Preparation method of hyaluronic acid-based bi-crosslinked hydrogel

A technology of hyaluronic acid and cross-linked hyaluronic acid, which is applied in the fields of pharmaceutical formulations, medical science, and prostheses, and can solve problems such as insufficient mechanical properties of injectable hydrogels, limited tissue engineering applications, and poor tissue adhesion. Achieve the effects of ensuring non-toxicity and cell compatibility, simple and easy-to-operate preparation process, and mild reaction conditions

Active Publication Date: 2020-06-19
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, injectable hydrogels often have insufficient mechanical properties, poor adhesion to tissues, and easy to fall off, which limits their application in tissue engineering.

Method used

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  • Preparation method of hyaluronic acid-based bi-crosslinked hydrogel
  • Preparation method of hyaluronic acid-based bi-crosslinked hydrogel
  • Preparation method of hyaluronic acid-based bi-crosslinked hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Dissolve 0.5g hyaluronic acid completely in 100mM morpholineethanesulfonic acid buffer at room temperature, add 0.7g carboxyl activator 4-(4,6-dimethoxytriazin-2-yl)-4-methanol After activating the carboxyl group with morpholine hydrochloride for 30 minutes, add 110 μL of furfurylamine, stir and react for 24 hours at room temperature in the dark, then add 0.7 g of 4-(4,6-dimethoxytriazin-2-yl)-4-methyl After activating the carboxyl group with morpholine hydrochloride for 30 minutes, add 0.7112 g of dopamine hydrochloride, stir and react for 24 hours, after the reaction, dialyze through a dialysis bag with a molecular weight cut-off of 8000-14000 for 4 days, and freeze-dry at -50°C to obtain furan and dopamine-modified hyaluronic acid .

[0031] Dissolve 0.5g hyaluronic acid completely in 100mM morpholineethanesulfonic acid buffer at room temperature, add 0.7g carboxyl activator 4-(4,6-dimethoxytriazin-2-yl)-4-methanol After activating the carboxyl group with morpholine...

Embodiment 2

[0037] Dissolve 0.5g hyaluronic acid completely in 100mM morpholineethanesulfonic acid buffer at room temperature, add 1.4g carboxyl activator 4-(4,6-dimethoxytriazin-2-yl)-4-methanol After activating the carboxyl group with morpholine hydrochloride for 30 minutes, add 110 μL of furfurylamine, stir and react for 24 hours at room temperature in the dark, then add 1.4 g of 4-(4,6-dimethoxytriazin-2-yl)-4-methyl After activating the carboxyl group with morpholine hydrochloride for 30 minutes, add 0.7112 g of dopamine hydrochloride, stir and react for 24 hours, after the reaction, dialyze through a dialysis bag with a molecular weight cut-off of 8000-14000 for 4 days, and freeze-dry at -50°C to obtain furan and dopamine-modified hyaluronic acid .

[0038] Dissolve 0.5g hyaluronic acid completely in 100mM morpholineethanesulfonic acid buffer at room temperature, add 1.4g carboxyl activator 4-(4,6-dimethoxytriazin-2-yl)-4-methanol After activating the carboxyl group with morpholine...

Embodiment 3

[0041] Example 3 (compression performance test of double cross-linked hydrogels at different pHs)

[0042] The 2% double cross-linked hydrogel was soaked in phosphate buffer solution with pH 6, 7.4 and 9 for 24 hours to make it swell completely. A dynamic mechanical analyzer was used to test the compressive properties of hydrogels that swelled completely under different pH phosphate buffers, and the obtained compression curves were as follows: Figure 5 shown. The results indicated that the mechanical properties of the hydrogel improved with the increase of pH. This is because as the pH increases, the more phenylboronate is formed, which improves the mechanical properties of the hydrogel to a certain extent.

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Abstract

The invention discloses a preparation method of hyaluronic acid-based double-crosslinked hydrogel, which comprises the following steps: respectively modifying hyaluronic acid to obtain furan- and dopamine-modified hyaluronic acid and furan- and phenylboronic acid-modified hyaluronic acid, blending the two modified hyaluronic acids with maleimide-terminated four-arm polyethylene glycol to generatedouble crosslinking, wherein the vicinal diol structures of phenylboronic acid and dopamine can spontaneously form phenylboronic acid ester under the condition that the pH value is 7.4 and the hydrogel has injectability and adhesion, producing single cross-linked hydrogel, and making the furan group and maleimide undergo a Diels-Alder reaction in subsequent time to form secondary cross-linking, sothat the mechanical property of the hydrogel is enhanced and the double cross-linked hydrogel is obtained. By adopting a double-crosslinking mode of click chemistry and phenylboronic acid ester, theobtained product has good mechanical properties, injectability, hyaluronidase degradation resistance and excellent biocompatibility, and the two crosslinking modes are mild and rapid and can encapsulate cells for injection.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a method for preparing a hyaluronic acid-based double-crosslinked hydrogel. Background technique [0002] Hydrogels are high water content systems composed of three-dimensional networks of hydrophilic polymers combined with water, and they have unique properties similar to natural ECMs, such as high water content, biodegradability, porosity and Biocompatible, versatile and attractive biomaterials for tissue engineering and cell therapy applications, the composition, structure, mechanical properties, and biochemical properties of hydrogels can be easily adjusted to suit various desired biomedical applications. Benefiting from the above advantages, hydrogels have been widely studied as tissue engineering repair materials, and their application fields include repair of soft tissues such as nerves, osteocartilage, skin, muscle, and blood vessels. [0003] Hyaluronic ac...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L5/08C08L71/02C08B37/08A61L27/20A61L27/50A61L27/52
CPCA61L27/20A61L27/50A61L27/52A61L2400/06A61L2430/06C08B37/0072C08J3/075C08J3/243C08J3/246C08J2305/08C08J2471/02C08L5/08
Inventor 曹晓东余晨希李庆涛
Owner SOUTH CHINA UNIV OF TECH
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