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Injectable self-healing hydrogel with adjustable mechanical properties as well as preparation method and application of injectable self-healing hydrogel

A self-healing, hydrogel technology, applied in medical science, pharmaceutical formulations, bandages, etc., can solve the problems of no further research on hemostasis and promotion of wound healing, prolonged gel time, and inability to inject smoothly, so as to promote wound healing. , Expand the scope of application, the effect of adjustable mechanical properties

Active Publication Date: 2020-08-11
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And the gelation time needs to be strictly controlled. If the gelation is too slow, the hydrogel will be diluted by the body fluid before being injected into the body, releasing the toxicity of the raw material and prolonging the gelation time; if the gelation is too fast, it will Clogged needle, unable to inject smoothly
Moreover, the hydrogel prepared by this patent only forms a single reversible imine bond with the primary amino groups of chitin derivatives and / or collagen by oxidizing the aldehyde groups of polysaccharides, which not only leads to lower mechanical strength, but also because More residual free aldehyde groups lead to greater cytotoxicity
In addition, the hydrogel prepared by this patent is only used to prepare intraocular fillings, and there is no further research on hemostasis and promotion of wound healing

Method used

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  • Injectable self-healing hydrogel with adjustable mechanical properties as well as preparation method and application of injectable self-healing hydrogel
  • Injectable self-healing hydrogel with adjustable mechanical properties as well as preparation method and application of injectable self-healing hydrogel
  • Injectable self-healing hydrogel with adjustable mechanical properties as well as preparation method and application of injectable self-healing hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Preparation of oxidized hyaluronic acid (OHA):

[0055] To 200 mL of 10 mg / mL hyaluronic acid aqueous solution, add 5 mL of 0.5 mol / L sodium periodate aqueous solution dropwise, and stir for 2 h in the dark; then add 1 mL of ethylene glycol, and continue stirring for 1 h; After water dialysis for 3 days, it was freeze-dried, and the molecular weight cut-off of the dialysis bag was 8-14KDa to obtain oxidized hyaluronic acid (OHA).

[0056] The hydrogen nuclear magnetic spectrum of the above-mentioned oxidized hyaluronic acid is as follows: figure 1 As shown, compared with hyaluronic acid (HA), a new aldehyde group characteristic peak appears in the OHA NMR spectrum at 4.9-5.0ppm, indicating that OHA was successfully synthesized.

Embodiment 2

[0058] Preparation of succinyl chitosan (NSC):

[0059] Chitosan is dispersed in dimethyl sulfoxide containing succinic anhydride, so that the concentration of chitosan in the reaction system is 50mg / mL; the amino group of chitosan: the molar ratio of succinic anhydride is 1:(1-2 ), stirred and reacted at 60°C for 1.5-4h and then centrifuged; dispersed the precipitate in water, adjusted the pH value to 10-12 with sodium hydroxide solution to form a yellow solution; added acetone to produce a precipitate; centrifuged to collect the precipitate, washed with acetone, and dried Succinyl chitosan (NSC) was obtained.

[0060] The proton nuclear magnetic spectrum of above-mentioned succinyl chitosan is as figure 2 As shown, compared with chitosan (CS), the characteristic peak of new methylene hydrogen appears in the NSC NMR spectrum at 2.40-2.49ppm, indicating that NSC was successfully synthesized.

Embodiment 3

[0062] A method for preparing an injectable self-healing hydrogel with adjustable mechanical properties, comprising the following steps:

[0063] (1) The OHA prepared in Example 1 was dissolved in the phosphate buffer solution of pH=7.4 to obtain a 60 mg / mL OHA solution; calcium chloride (CaCl 2 ) was dissolved in water to obtain 120 mg / mL calcium chloride aqueous solution; OHA solution and calcium chloride aqueous solution were mixed, wherein the mass ratio of OHA and calcium chloride was 1:0.1 to obtain OHA composite solution 1;

[0064] (2) Dissolve the NSC prepared in Example 2 in a phosphate buffer solution with pH=7.4 to obtain a 60 mg / mL NSC solution;

[0065] (3) Mix the OHA composite solution 1 in step (1) with the NSC solution in step (2), the mass ratio of the two is 1:1, and the cross-linking reaction is 30-60 seconds at 25-37°C to obtain NSC- OHA-Ca2 hydrogel.

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Abstract

The invention relates to an injectable self-healing hydrogel with adjustable mechanical properties as well as a preparation method and application of the injectable self-healing hydrogel. The hydrogeldisclosed by the invention is prepared from the following raw materials: oxidized hyaluronic acid and succinyl chitosan, and further is prepared from one or more of calcium ions, polyethylene glycolderivatives, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. According to the invention, hyaluronic acid and succinyl chitosan are oxidized; introducing one or more of calcium ions, a polyethylene glycol derivative, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) is adopted; the self-healing and injectable hydrogel is prepared by adjusting the components and the component content of the hydrogel, so that the hydrogel has the characteristic of adjustable mechanical properties, and the biocompatibility, hemostasis, wound healing promotion, angiogenesis promotion and other properties of the hydrogel are improved.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to an injectable self-healing hydrogel with adjustable mechanical properties and a preparation method and application thereof. Background technique [0002] Tissue bleeding and trauma are very common in daily life and clinical practice. Therefore, we should pay attention to promoting wound repair and reducing scar formation while stopping bleeding. Hydrogels are widely used in biomedical materials because they are similar in structure to extracellular matrix, have a soft and high water content 3D structure, and are conducive to cell growth, adhesion, and secretion of growth factors. The hydrogel can absorb water in the blood, enrich platelets and blood cells, and keep the wound moist, thus playing the role of hemostasis and wound healing. However, most of the hydrogels currently studied are prefabricated hydrogels, which are difficult to fill and cover irre...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L71/02C08K3/16A61L26/00C08B37/08
CPCA61L26/0019A61L26/0023A61L26/008A61L2400/06C08B37/003C08B37/0072C08J3/075C08J3/24C08J2305/08C08J2471/02C08K2003/162
Inventor 陈宗刚翁洪娟贾维彬顾国锋郭忠武
Owner SHANDONG UNIV
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