WO2016107110A1 - Hydroxyapatite nerve scaffold and manufacturing method therefor - Google Patents

Abstract

A hydroxyapatite nerve scaffold comprising a scaffold membrane (1) and a degradable metal wire (2) wrapped by the scaffold membrane (1). The primary constituent of the scaffold membrane (1) is hydroxyapatite. The artificial nerve scaffold manufactured per the method has great mechanical properties, is biodegradable, provides a three-dimensional structure required for neuroregeneration, and has profound significance in neurorestoration.

Description

Hydroxyapatite nerve scaffold and preparation method thereof Technical field

The invention relates to the technical field of nerve stents, in particular to a hydroxyapatite nerve stent and a preparation method thereof.

Background technique

Peripheral nerve damage or breakage due to various trauma causes a decrease or loss of sensory and motor function. Severe peripheral nerve injury often leads to paralysis or permanent loss of labor. Peripheral nerve injury has a high incidence in China. According to statistics, in trauma patients, nerve injury of the extremities accounts for about 10% of the total number of trauma, and about 60% of the fractures of firearm injuries have neurological injuries. To this end, we need to find the ideal treatment for peripheral nerve injury. For peripheral nerve fractures, if the fracture gap is large, the fractured peripheral nerve must be regenerated and repaired by bridging the graft.

Currently, commonly used implants include autografts and artificial nerve stents. Autologous grafts have limited sources and can cause donor sequelae. In terms of artificial nerve stents, the development of non-degradable catheter materials may lead to nerve compression and the risk of secondary surgery. In recent years, research has mainly led to the development and research of biodegradable stent materials. Currently, the United States has approved a variety of brands, such as NeuraGen, SaluBridge, Neurolac and other nerve catheters for clinical use. However, China's research on nerve scaffolds is relatively backward, and no neural catheters with independent intellectual property rights have been developed.

Hydroxyapatite is the main inorganic component of human and animal bones and teeth. Its physical and chemical composition is very similar to the inorganic composition of human bone. It has good biocompatibility, bioactivity and osteoconductivity, and human bone tissue. Excellent chemical and biological affinity. Bioactive ceramics prepared from hydroxyapatite are not only safe, non-toxic, but also capable of conducting bone growth. However, the use of hydroxyapatite for the preparation of nerve scaffolds for nerve repair has not been reported so far.

Summary of the invention

In order to overcome the deficiencies of the prior art, the present invention provides a hydroxyapatite nerve scaffold and a preparation method thereof. The neural scaffold prepared by the method has good mechanical properties, is biodegradable, and has a three-dimensional structure required for nerve regeneration. Repair has far-reaching significance.

The technical scheme of the present invention is as follows: a hydroxyapatite nerve stent comprising a stent film and a degradable metal wire wrapped by a stent film, and the main component of the stent film is hydroxyapatite.

The stent is in the form of a sheet, a strip or a cylinder.

The degradable wires are distributed along the lateral and longitudinal directions of the stent.

The main component of the degradable metal wire is magnesium, zinc, calcium, iron or an alloy thereof.

The preparation method of the hydroxyapatite nerve stent comprises the following steps:

1) Preparation of binder: Weigh 3g of carboxymethyl cellulose dissolved in 60ml of distilled water, heated to 40 ° C with a temperature-controlled magnetic stirrer and stirred for 30min until the solution is clarified to obtain a carboxymethyl cellulose solution;

2) Preparation of hydroxyapatite slurry: hydroxyapatite powder was taken, calcined at 900 ° C for 3 hours, cooled and dissolved in distilled water, and ultrasonically shaken for 30 min to make it uniformly dispersed to obtain a hydroxyapatite slurry. The mass concentration is 10-50%;

3) Preparation of the stent film: 1-1.5% by volume of the carboxymethyl cellulose solution obtained in the step 1 was added to the hydroxyapatite slurry obtained in the step 2), stirred for 1 hour with a magnetic stirrer, and allowed to stand in a vacuum box for 24 hours. Removing the gas in the slurry to obtain the stent film material;

4) injecting the stent film into a cavity of a special mold, and disposing a degradable wire in a lateral direction and a longitudinal direction in a molding direction of the stent film, freezing at -10-70 ° C, and then taking out the mold The equipment is pumped up, connected to a vacuum pump, placed in a freezer for vacuum drying; then, at a high temperature of 200-400 ° C, the methyl cellulose is removed, and then sintered at 1000-1200 for 2-6 hours to obtain the hydroxyl group. Apatite nerve support.

The nerve scaffold has a porosity of 40-65%.

The beneficial effects of the invention are as follows: the hydroxyapatite nerve scaffold of the invention has good mechanical properties, biodegradability, and has the three-dimensional structure required for nerve regeneration, and has profound significance for nerve repair.

BRIEF DESCRIPTION OF THE DRAWINGS:

1 is a schematic view showing the structure of a hydroxyapatite nerve stent according to the present invention.

Figures 2a, 2b and 2c are photographs of the upper surface, lower surface and longitudinal surface of the resulting hydroxyapatite nerve stent observed under a microscope.

detailed description

The present invention will be further described below in conjunction with the drawings and preferred embodiments, but the embodiments of the present invention are not limited thereto.

Referring to Fig. 1, a hydroxyapatite nerve stent comprises a stent film 1 and a degradable metal wire 2 wrapped by a stent film 1. The degradable wires are distributed along the lateral and longitudinal directions of the stent. The stent can be prepared into various shapes according to the needs of use, and is generally cylindrical or sheet-shaped. The nerve scaffold has a porosity of 40-65%.

The stent film 1 is hydroxyapatite. The main component of the degradable metal wire 2 is magnesium, zinc, calcium, iron or an alloy thereof.

Embodiment 1, a method for preparing a hydroxyapatite nerve stent, comprising the following steps:

1) Preparation of binder: Weigh carboxymethyl cellulose dissolved in distilled water, heated to 40 ° C with a temperature-controlled magnetic stirrer and stirred for 30 min until the solution is clarified to obtain a carboxymethyl cellulose solution with a mass concentration of 5%. ;

2) Preparation of hydroxyapatite slurry: hydroxyapatite powder was taken, calcined at 900 ° C for 3 hours, cooled and dissolved in distilled water, and ultrasonically shaken for 30 min to make it uniformly dispersed to obtain a hydroxyapatite slurry. The mass concentration is 40%;

3) Preparation of the stent film: 1.5% by volume of the carboxymethyl cellulose solution obtained in the step 1 was added to the hydroxyapatite slurry obtained in the step 2), stirred for 1 hour with a magnetic stirrer, and allowed to stand in a vacuum box for 24 hours. a gas in the slurry to obtain the scaffold film;

4) injecting the stent film into a cavity of a special mold, disposing a degradable wire in a lateral direction and a longitudinal direction in a molding direction of the stent film, freezing at -10 ° C, and then taking out the mold into a pumping device And connected to a vacuum pump, placed in a freezer for vacuum drying; then, at 200-400 ° C high temperature, remove methyl cellulose, and then sintered at 1050 for 2-6 hours to obtain the hydroxyapatite nerve stent .

Figures 2a, 2b and 2c are photographs of the upper surface, lower surface and longitudinal surface of the artificial nerve stent obtained under a microscope.

Embodiment 2, a method for preparing a hydroxyapatite nerve stent, comprising the following steps:

1) Preparation of binder: Weigh carboxymethyl cellulose dissolved in distilled water, heated to 40 ° C with a temperature-controlled magnetic stirrer and stirred for 30 min until the solution is clarified to obtain a carboxymethyl cellulose solution with a mass concentration of 3%. ;

2) Preparation of hydroxyapatite slurry: hydroxyapatite powder is taken, calcined at 800-° C. for 3 hours, cooled, dissolved in distilled water, and shaken by ultrasonic for 40 min to uniformly disperse to obtain a hydroxyapatite slurry. Its mass concentration is 50%;

3) Preparation of the stent film: 1% by volume of the carboxymethyl cellulose solution obtained in the step 1 was added to the hydroxyapatite slurry obtained in the step 2), stirred for 1 hour with a magnetic stirrer, and allowed to stand in a vacuum box for 24 hours. a gas in the slurry to obtain the scaffold film;

4) injecting the stent film into a cavity of a special mold, disposing a degradable wire in a lateral direction and a longitudinal direction in a molding direction of the stent film, freezing at -70 ° C, and then taking out the mold into a pumping device And connected to a vacuum pump, placed in a freezer for vacuum drying; then, at 200-400 ° C high temperature, remove methyl cellulose, and then sintered at 1000-1200 for 2-6 hours to obtain the hydroxyapatite Nerve stent.

The above is a further detailed description of the present invention in connection with the specific preferred embodiments, and the specific embodiments of the present invention are not limited to the description. For those skilled in the art to which the present invention pertains, the architectural form can be flexible and can be derived from a series of products without departing from the inventive concept. It is to be understood that the invention is intended to be limited to the scope of the invention as defined by the appended claims.

Claims (6)

A hydroxyapatite nerve scaffold characterized by comprising a scaffold film and a degradable metal wire wrapped by a scaffold film, the main component of the scaffold film being hydroxyapatite. The hydroxyapatite nerve stent according to claim 1, wherein the stent is in the form of a sheet, an elongated strip or a cylinder. The hydroxyapatite nerve stent according to claim 1, wherein the degradable metal wire is distributed along a lateral direction and a longitudinal direction of the stent. The hydroxyapatite nerve stent according to claim 1, wherein the main component of the degradable metal wire is magnesium, zinc, calcium, iron or an alloy thereof. The method for preparing a hydroxyapatite nerve stent according to any one of claims 1 to 4, comprising the steps of: 1) Preparation of binder: Weigh 3g of carboxymethyl cellulose dissolved in 60ml of distilled water, heated to 40 ° C with a temperature-controlled magnetic stirrer and stirred for 30min until the solution is clarified to obtain a carboxymethyl cellulose solution; 2) Preparation of hydroxyapatite slurry: hydroxyapatite powder was taken, calcined at 900 ° C for 3 hours, cooled and dissolved in distilled water, and ultrasonically shaken for 30 min to make it uniformly dispersed to obtain a hydroxyapatite slurry. The mass concentration is 10-50%; 3) Preparation of the stent film: 1-1.5% by volume of the carboxymethyl cellulose solution obtained in the step 1 was added to the hydroxyapatite slurry obtained in the step 2), stirred for 1 hour with a magnetic stirrer, and allowed to stand in a vacuum box for 24 hours. Removing the gas in the slurry to obtain the stent film material; 4) injecting the stent film into a cavity of a special mold, and disposing a degradable wire in a lateral direction and a longitudinal direction in a molding direction of the stent film, freezing at -10-70 ° C, and then taking out the mold The equipment is pumped up, connected to a vacuum pump, placed in a freezer for vacuum drying; then, at a high temperature of 200-400 ° C, the methyl cellulose is removed, and then sintered at 1000-1200 for 2-6 hours to obtain the hydroxyl group. Apatite nerve support. The method for preparing a hydroxyapatite nerve stent according to claim 5, wherein the nerve stent has a porosity of 40-65%.

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