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Injectable silk fibroin/nano-hydroxyapatite composite hydrogel and preparation method thereof

A nano-hydroxyapatite and hydroxyapatite technology, applied in pharmaceutical formulations, medical science, prostheses, etc., can solve the limitations of popularization, application and performance, difficulty in storage and transportation of hydrogel raw materials, interface bonding strength, mixing It is difficult to guarantee the scale and uniformity, so as to achieve the effect of easy industrialization and popularization and application, efficient and fast preparation method, and meet the needs of clinical application.

Pending Publication Date: 2021-08-06
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above method is essentially physical mixing, not a combination of chemical bonds, and its interface bonding strength, mixing scale and uniformity are difficult to guarantee
In addition, the regenerated silk fibroin solution is extremely unstable, and even if it is stored at low temperature, it will spontaneously form a gel over time. The preparation, transportation and preservation of the drug have brought great inconvenience, and the preparation process is very complicated and cumbersome, thus limiting its clinical application and effectiveness.
Because hydroxyapatite has good biocompatibility and osteoinductivity, it is often used as a material for injectable hydrogels. However, hydrogel products prepared from hydroxyapatite are currently facing many problems: hydroxyapatite Stone powder is prone to agglomeration due to its small particle size, resulting in uneven distribution of inorganic phases in composite materials, difficulty in removing air bubbles, and difficulty in storage and transportation of hydrogel raw materials.

Method used

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  • Injectable silk fibroin/nano-hydroxyapatite composite hydrogel and preparation method thereof
  • Injectable silk fibroin/nano-hydroxyapatite composite hydrogel and preparation method thereof
  • Injectable silk fibroin/nano-hydroxyapatite composite hydrogel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] (1) Select 0.05% Na 2 CO 3 20g silkworm cocoons were degummed with 1L of the solution, washed and dried to obtain silk fibroin fibers.

[0048] (2) Dissolve 5 g of silk fibroin fibers with 50 ml of calcium chloride / ethanol / water (molar ratio 1:2:8) ternary system solution at 70°C to obtain 10% (w / v) silk fibroin fibers. protein mixture solution.

[0049] (3) At 37°C, gradually add 10.0 g of ammonium dihydrogen phosphate to the silk fibroin mixed solution obtained in step (2) according to the molar ratio of calcium: phosphorus of 10:6, and use 2M ammonia water to adjust the pH value to 10.0, stirring and reacting for 6 hours; after the reaction, the silk fibroin / nano-hydroxyapatite composite solution was obtained by dialysis.

[0050] (4) The silk fibroin / nano-hydroxyapatite composite solution obtained in step (3) is induced with ultrasonic power of 250 watts and the ultrasonic power ratio is 90% for 1 min to obtain injectable silk fibroin / nano-hydroxyapatite Apatite...

Embodiment 2

[0052] (1) Select 0.05% Na 2 CO 3 20g silkworm cocoons were degummed with 1L of the solution, washed and dried to obtain silk fibroin fibers.

[0053] (2) Dissolve 15g of silk fibroin fiber with 50ml of calcium chloride / ethanol / water (molar ratio: 1:2:8) ternary system solution at 70°C to obtain 15% (w / v) silk protein mixture solution.

[0054] (3) At 60°C, gradually add 15.0 g of diammonium hydrogen phosphate to the silk fibroin mixed solution obtained in step (2) at a molar ratio of calcium: phosphorus of 10:6, and use 2M sodium hydroxide to adjust the pH value to 9.0, stirred for 4 hours; after the reaction, the silk fibroin / nano-hydroxyapatite composite solution was obtained by dialysis.

[0055] (4) The silk fibroin / nano-hydroxyapatite composite solution obtained in step (3) is induced with ultrasonic power of 250 watts and the ultrasonic power ratio is 30% for 2 minutes to obtain injectable silk fibroin / nano-hydroxyapatite Apatite composite hydrogel; the silk fibroin...

Embodiment 3

[0057] (1) Select 0.05% Na 2 CO 3 The solution degummed 20 g silkworm cocoons, washed and dried to obtain silk fibroin fibers.

[0058] (2) Dissolve 5g of silk fibroin fiber with 100ml of calcium chloride / ethanol / water (molar ratio is 1:2:8) ternary system solution at 75°C to obtain 5% (w / v) silk fibroin protein mixture solution.

[0059] (3) At 60°C, gradually add 30 g of diammonium hydrogen phosphate to the silk fibroin mixed solution obtained in step (2) according to the molar ratio of calcium: phosphorus of 10:6, and adjust the pH value to 10 with ammonia water, The reaction was stirred for 2 hours; after the reaction, the silk fibroin / nano hydroxyapatite composite solution was obtained by dialysis.

[0060] (4) The silk fibroin / nanometer hydroxyapatite composite solution obtained in step (3) is induced with ultrasonic power of 250 watts and an ultrasonic power ratio of 70% for 0.5 min to obtain injectable silk fibroin / nano Hydroxyapatite composite hydrogel; the silk f...

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Abstract

The invention provides injectable silk fibroin / nano-hydroxyapatite composite hydrogel and a preparation method thereof. The preparation method comprises the following steps that silkworm cocoons are degummed and dried to obtain silk fibroin, the silk fibroin is dissolved with a solvent at a certain temperature and then mixed with phosphate to obtain a mixed solution, the pH value of the mixed solution is adjusted, and after reaction is conducted for a period of time, performing dialyzing and drying to obtain silk fibroin / nano-hydroxyapatite powder, and then performing ultrasonic treatment to generate the silk fibroin / nano-hydroxyapatite composite hydrogel. The mass volume concentration of the silk fibroin / hydroxyapatite powder is 0.1%-90%; The mass ratio of the silk fibroin to the hydroxyapatite is (5-99): (1-95). The prepared composite hydrogel is uniform, good in interface bonding, free of bubbles inside, safe, non-toxic and excellent in injectability. The method is simple in preparation process, mild in condition, free of chemical cross-linking agents in the whole process, environmentally friendly, low in cost and easy to industrialize, popularize and apply.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to an injectable silk fibroin / nanometer hydroxyapatite composite hydrogel and a preparation method thereof. Background technique [0002] Hydrogel is a kind of cross-linked polymer with a three-dimensional network structure, which can well simulate the water environment of the extracellular matrix, and provide a microenvironment similar to the natural extracellular matrix for cell adhesion, proliferation and differentiation. It is an ideal material for repair and reconstruction, so it is widely used in biomedical fields, such as medical dressings, cartilage tissue repair, cell transplantation, drug delivery and tissue engineering scaffolds, etc., especially injectable hydrogels for tissue repair. Attractive, it can not only be transplanted to the defect site in a minimally invasive manner, but also can fill defects of any shape, and at the same time facilitate the loadi...

Claims

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Application Information

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IPC IPC(8): A61L27/22A61L27/12A61L27/50A61L27/52
CPCA61L27/227A61L27/12A61L27/50A61L27/52A61L2400/12A61L2400/06
Inventor 肖芸龙仕和吴永豪朱向东张兴栋
Owner SICHUAN UNIV
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