阅读说明：本技术 一种3d打印内壁微图案化神经导管的简易制备方法 (Simple preparation method of 3D printing inner wall micropatterned nerve conduit ) 是由 张强强 张靖翔 王记增 张宝强 刘鐘阳 王静 于 2021-07-07 设计创作，主要内容包括：本发明涉及3D打印技术领域,具体为一种3D打印内壁微图案化神经导管的简易制备方法,提出了一种快速、便捷、简易、低成本、适用多种生物材料的制备内壁微图案、侧壁无缝的一体化神经导管制备方法；其包括打印装置的搭建和墨水配置、打印及交联；该方法依托直接书写式3D打印系统,将“墨水”直接打印在具有微图案结构的钨钢棒上,交联固化后直接取下。与传统工艺相比,该方法不但具有同样精细度的微图案结构和无缝侧壁,并且操作简单、制备快速,设备一次搭建便可一直重复使用。本方法基于3D打印技术提出了一种快速、便捷、简易、低成本、适用多种生物材料的制备内壁微图案、侧壁无缝的一体化神经导管制备方法。(The invention relates to the technical field of 3D printing, in particular to a simple preparation method of a 3D printing inner wall micro-patterning nerve conduit, and provides a rapid, convenient, simple, low-cost and seamless side wall integrated nerve conduit preparation method suitable for preparing inner wall micro-patterns by using various biological materials; the method comprises the steps of constructing a printing device, configuring ink, printing and crosslinking; the method is based on a direct writing type 3D printing system, and the 'ink' is directly printed on a tungsten steel bar with a micro-pattern structure and is directly taken down after being crosslinked and cured. Compared with the traditional process, the method has the advantages that the micro-pattern structure and the seamless side wall with the same fineness are provided, the operation is simple, the preparation is rapid, and the equipment can be repeatedly used after being built once. The method provides an integrated nerve conduit preparation method which is rapid, convenient, simple, low in cost, suitable for preparing inner wall micro-patterns and side wall seamless and applicable to various biological materials based on a 3D printing technology.)

1. A simple preparation method of a 3D printing inner wall micropatterned nerve conduit is characterized by comprising the following steps:

the method comprises the following steps: the printing device comprises a bottom plate (1), wherein an ink printing device, a moving device, a supporting plate (16) and an ultraviolet curing lamp (17) are mounted on the bottom plate (1), and the moving device is mounted below the ink printing device; the ink printing device comprises a first upright post (2) fixed on a bottom plate (1), the upper part of the first upright post (2) is connected with a cross rod (4) through a connecting block (3), a material barrel (5) is installed at the right end of the cross rod (4), and a needle head (6) is installed at the bottom of the material barrel (5); the moving device comprises a first stepping motor (7) and a fixed block (9) which are installed on a bottom plate (1), a screw rod (10) is connected onto an output shaft of the first stepping motor (7), the other end of the screw rod (10) is connected with the fixed block (9) through a bearing, a sliding block (8) is in threaded connection with the middle of the screw rod (10), two guide rods (11) are fixedly connected between the first stepping motor (7) and the fixed block (9), the two guide rods (11) are located on two sides of the screw rod (10), the two guide rods (11) are in clearance connection with the sliding block (8), a moving platform (12) is fixedly connected to the upper surface of the sliding block (8), a second upright column (13) is fixedly connected to the upper surface of the moving platform (12), a second stepping motor (14) is installed at the top of the second upright column (13), a tungsten steel bar (15) is installed on an output shaft of the second stepping motor (14), the other end of the tungsten steel bar (15) is inserted into a supporting plate (16), and ultraviolet curing lamps (17) are placed on two sides of the moving device;

step two: configuring, printing and crosslinking ink, namely configuring one or more of methacrylic acidylated gelatin, sodium alginate, chitosan, polyvinyl alcohol and the like into printing ink with a certain concentration, discharging gas in the printing ink in a vacuum auxiliary mode, then filling the configured printing ink into a printing cylinder, and extruding the printing ink out of a needle head by adjusting the air pressure of a propeller; enabling the tungsten steel bar (15) to rotate along the central axis through the second stepping motor (14), enabling the moving platform (12) to transversely move at a constant speed through the first stepping motor (7), and enabling the biological ink to be uniformly printed on the tungsten steel bar (15) through adjusting numerical values of the tungsten steel bar, the moving platform and the moving platform; if the printing ink is methacrylic acid acylated gelatin and the like which need to be crosslinked under the condition of ultraviolet light, the ultraviolet light curing lamps on the two sides are turned on in the printing process, and if other conditions need to be crosslinked, the tungsten steel bar is taken down and placed in other crosslinking environments.

2. The simple preparation method of the 3D printing inner wall micropatterned nerve conduit according to claim 1, characterized in that: in the first step, the diameter of the tungsten steel bar (15) is 1-3mm, and the surface of the tungsten steel bar (15) is subjected to micro-pattern structuring treatment.

3. The simple preparation method of the 3D printing inner wall micropatterned nerve conduit according to claim 1, characterized in that: in the first step, the tungsten steel bar (15) is positioned on the light path of two ultraviolet curing lamps (17).

4. The simple preparation method of the 3D printing inner wall micropatterned nerve conduit according to claim 1, characterized in that: in the first step, the first stepping motor 7 drives the screw rod 10 to rotate, so that the moving platform 12 is driven by the sliding block 8 to move transversely.

5. The simple preparation method of the 3D printing inner wall micropatterned nerve conduit according to claim 1, characterized in that: in the first step, the second stepping motor (14) drives the tungsten steel bar (15) to rotate.

6. The simple preparation method of the 3D printing inner wall micropatterned nerve conduit according to claim 1, characterized in that: in the first step, the material cylinder (5) is connected with a propeller, so that the ink is uniformly distributed on the tungsten steel bar (15) through a needle (6) under the pressure of the propeller.

Technical Field

The invention relates to the technical field of 3D printing, in particular to a simple preparation method of a 3D printing inner wall micropatterned nerve conduit.

Background

Peripheral nerve injury is a common disease, can cause movement and sensory disturbance of innervation areas of patients, and brings great negative effects on daily life, mental health and the like. Although peripheral nerves have a certain self-repairing ability, long-distance nerve defects caused by tumors, trauma, etc. must be treated by other means. At present, autologous nerve transplantation is the "gold standard" for peripheral nerve regeneration, but the method has the problems of severe donor deficiency, inevitable secondary damage to donor sites and the like. Therefore, artificial nerve repair catheters have become a hotspot in modern medical research.

An ideal nerve conduit would provide sufficient mechanical strength to act as a bridge between damaged nerve endings. On one hand, the invasion of surrounding tissues can be prevented; on the other hand, the damaged nerve can be regenerated along the direction of the catheter, and support and nutrition are provided for nerve regeneration. Among them, how to guide the nerve cells to migrate directionally is the most important issue. Previous researches show that the surface micro-pattern structure (groove structure) of the biomaterial scaffold can induce the directional migration of cells so as to induce the rapid growth of tissues, and at present, the method is successfully applied to the repair of tissues such as skin, muscle and the like. The planar micro-pattern structure (groove structure) is simple in construction method, but nerves are three-dimensional tissues, so that the difficulty of the preparation process of the micro-pattern structure (groove structure) is greatly increased, and the application of the structure in a nerve conduit is limited. At present, a great deal of research is conducted on preparing a planar micropattern structure (groove structure), then forming a cylinder by a curl method, and then performing sealing treatment such as sewing on the edge of the cylinder. Nevertheless, the sutures and suture recesses in the side wall of the catheter may cause an inflammatory response, and nutrient leakage or neurite outgrowth may occur at the suture site, resulting in implant failure. The preparation method of the nerve conduit with seamless side wall needs to carry out the processes of etching, casting, pouring, forming, re-casting, re-pouring and the like for many times, and each process needs to ensure the accuracy, thereby greatly increasing the processing steps and the complexity.

In order to avoid the complicated steps and processes of multiple processing and prevent the implantation failure caused by the leakage of the side wall, the development of an integrated nerve conduit preparation technology which can simply prepare micro-patterns on the inner wall and has seamless side wall is urgent.

Disclosure of Invention

The invention aims to provide a simple preparation method of a 3D printing inner wall micropatterned nerve conduit, and provides a rapid, convenient, simple, low-cost and seamless side wall integrated nerve conduit preparation method suitable for preparing inner wall micropatterns by using various biological materials.

In order to achieve the purpose, the invention adopts the following technical scheme:

a simple preparation method of a 3D printing inner wall micropatterned nerve conduit is characterized by comprising the following steps:

the method comprises the following steps: the method comprises the following steps of (1) constructing a printing device, wherein the printing device comprises a bottom plate 1, an ink printing device, a moving device, a supporting plate 16 and an ultraviolet curing lamp 17 are installed on the bottom plate 1, and the moving device is installed below the ink printing device; the ink printing device comprises a first upright post 2 fixed on a bottom plate 1, the upper part of the first upright post 2 is connected with a cross rod 4 through a connecting block 3, the right end of the cross rod 4 is provided with a material barrel 5, and the bottom of the material barrel 5 is provided with a needle 6; the moving device comprises a first stepping motor 7 and a fixed block 9 which are installed on a bottom plate 1, a screw rod 10 is connected to an output shaft of the first stepping motor 7, the other end of the screw rod 10 is connected with the fixed block 9 through a bearing, a sliding block 8 is in threaded connection with the middle of the screw rod 10, two guide rods 11 are fixedly connected between the first stepping motor 7 and the fixed block 9, the two guide rods 11 are located on two sides of the screw rod 10, the two guide rods 11 are in clearance connection with the sliding block 8, a moving platform 12 is fixedly connected to the upper surface of the sliding block 8, a second upright column 13 is fixedly connected to the upper surface of the moving platform 12, a second stepping motor 14 is installed at the top of the second upright column 13, a tungsten steel rod 15 is installed on an output shaft of the second stepping motor 14, and a support plate 16 is inserted into the other end of the tungsten steel rod 15, the ultraviolet curing lamps 17 are arranged on two sides of the mobile device;

step two: configuring, printing and crosslinking ink, namely configuring one or more of methacrylic acidylated gelatin, sodium alginate, chitosan, polyvinyl alcohol and the like into printing ink with a certain concentration, discharging gas in the printing ink in a vacuum auxiliary mode, then filling the configured printing ink into a printing cylinder, and extruding the printing ink out of a needle head by adjusting the air pressure of a propeller; enabling the tungsten steel bar 15 to rotate along the central axis through the second stepping motor 14, enabling the moving platform 12 to transversely move at a constant speed through the first stepping motor 7, and enabling the biological ink to be uniformly printed on the tungsten steel bar 15 through adjusting numerical values of the tungsten steel bar 15, the moving platform and the biological ink; if the printing ink is methacrylic acid acylated gelatin and the like which need to be crosslinked under the condition of ultraviolet light, the ultraviolet light curing lamps on the two sides are turned on in the printing process, and if other conditions need to be crosslinked, the tungsten steel bar is taken down and placed in other crosslinking environments.

Preferably, in the first step, the diameter of the tungsten steel rod 15 is 1-3mm, and the surface of the tungsten steel rod 15 is subjected to micropatterning (groove structure) treatment.

Preferably, in the step one, the tungsten steel rod 15 is positioned in the optical path of two ultraviolet curing lamps 17.

Preferably, in step one, the first stepping motor 7 (servo motor) rotates the screw rod 10, so that the moving platform 12 is moved laterally by the sliding block 8.

Preferably, in the first step, the second stepping motor 14 (servo motor) drives the tungsten steel bar 15 to rotate.

Preferably, in step one, the cartridge 5 is connected to a pusher so that the ink is evenly distributed on the tungsten steel rod 15 through the needle 6 under the pressure of the pusher.

The invention has the beneficial effects that: the method is based on a direct writing type 3D printing system, and the 'ink' is directly printed on a tungsten steel bar with a micro-pattern structure (groove structure), and is directly taken down after being crosslinked and cured. Compared with the traditional process, the method has the advantages that the micro-pattern structure (groove structure) and the seamless side wall with the same fineness are provided, the operation is simple, the preparation is quick, and the equipment can be repeatedly used all the time after being built once. The method provides an integrated nerve conduit preparation method which is rapid, convenient, simple, low in cost, suitable for preparing inner wall micro-patterns and side wall seamless and applicable to various biological materials based on a 3D printing technology.

Drawings

FIG. 1 is a flow chart of the preparation of a 3D printed inner wall micro-patterned nerve conduit of the present invention;

FIG. 2 is a schematic diagram of a printing apparatus according to the present invention;

FIG. 3 is a scanning electron microscope image of a W-steel bar after micro-pattern (groove structure) processing according to the present invention;

fig. 4 is a 3D printed macro picture of the calcium alginate nerve conduit and a micro pattern (groove structure) on the inner wall of the nerve conduit.

Shown in the figure: the device comprises a base plate 1, a first upright post 2, a connecting block 3, a cross rod 4, a charging barrel 5, a needle 6, a first stepping motor 7, a sliding block 8, a fixed block 9, a spiral rod 10, a guide rod 11, a moving platform 12, a second upright post 13, a second stepping motor 14, a tungsten steel bar 15, a supporting plate 16 and an ultraviolet curing lamp 17.

Detailed Description

The following detailed description of embodiments of the present invention is provided in connection with the accompanying drawings and examples. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Example 1

A simple preparation method of a 3D printing inner wall micropatterned nerve conduit is characterized by comprising the following steps as shown in figure 1:

the method comprises the following steps: the printing device is constructed, as shown in fig. 2, the printing device comprises a bottom plate 1, an ink printing device, a moving device, a support plate 16 and an ultraviolet curing lamp 17 are mounted on the bottom plate 1, and the moving device is mounted below the ink printing device; the ink printing device comprises a first upright post 2 fixed on a bottom plate 1, the upper part of the first upright post 2 is connected with a cross rod 4 through a connecting block 3, the right end of the cross rod 4 is provided with a material barrel 5, and the bottom of the material barrel 5 is provided with a needle 6; the moving device comprises a first stepping motor 7 and a fixed block 9 which are installed on a bottom plate 1, a screw rod 10 is connected to an output shaft of the first stepping motor 7, the other end of the screw rod 10 is connected with the fixed block 9 through a bearing, a sliding block 8 is in threaded connection with the middle of the screw rod 10, two guide rods 11 are fixedly connected between the first stepping motor 7 and the fixed block 9, the two guide rods 11 are located on two sides of the screw rod 10, the two guide rods 11 are in clearance connection with the sliding block 8, a moving platform 12 is fixedly connected to the upper surface of the sliding block 8, a second upright column 13 is fixedly connected to the upper surface of the moving platform 12, a second stepping motor 14 is installed at the top of the second upright column 13, a tungsten steel rod 15 is installed on an output shaft of the second stepping motor 14, and a support plate 16 is inserted into the other end of the tungsten steel rod 15, the ultraviolet curing lamps 17 are arranged on two sides of the mobile device;

step two: configuring, printing and crosslinking ink, namely configuring one or more of methacrylic acidylated gelatin, sodium alginate, chitosan, polyvinyl alcohol and the like into printing ink with a certain concentration, discharging gas in the printing ink in a vacuum auxiliary mode, then filling the configured printing ink into a printing cylinder, and extruding the printing ink out of a needle head by adjusting the air pressure of a propeller; enabling the tungsten steel bar 15 to rotate along the central axis through the second stepping motor 14, enabling the moving platform 12 to transversely move at a constant speed through the first stepping motor 7, and enabling the biological ink to be uniformly printed on the tungsten steel bar 15 through adjusting numerical values of the tungsten steel bar 15, the moving platform and the biological ink; if the printing ink is methacrylic acid acylated gelatin and the like which need to be crosslinked under the condition of ultraviolet light, the ultraviolet light curing lamps on the two sides are turned on in the printing process, and if other conditions need to be crosslinked, the tungsten steel bar is taken down and placed in other crosslinking environments.

Preferably, in the first step, as shown in fig. 3, the diameter of the sendust rod 15 is 1-3mm, and the surface of the sendust rod 15 is processed with a micro-pattern structure (groove structure).

Preferably, in the step one, the tungsten steel rod 15 is positioned in the optical path of two ultraviolet curing lamps 17.

Preferably, in step one, the first stepping motor 7 (servo motor) rotates the screw rod 10, so that the moving platform 12 is moved laterally by the sliding block 8.

Preferably, in the first step, the second stepping motor 14 (servo motor) drives the tungsten steel bar 15 to rotate.

Preferably, in step one, the cartridge 5 is connected to a pusher so that the ink is evenly distributed on the tungsten steel rod 15 through the needle 6 under the pressure of the pusher.

Example 2

As shown in fig. 4, fig. 4(a) is a 3D printed calcium alginate nerve conduit macro picture, and fig. 4(b) is a 3D printed calcium alginate nerve conduit inner wall micro pattern (groove structure) picture.

Taking sodium alginate printing ink as an example: sodium alginate is prepared into biological ink (the concentration is 100-300 mg/mL), and the biological ink is placed in 10-1000mg/mL CaCl after being printed₂Soaking in the solution for 1-24h to ensure sufficient crosslinking, placing the sample in deionized water for 1-36h, and removing excessive CaCl₂And taking down the sample to obtain the integrated calcium alginate nerve conduit with the micro-pattern on the inner wall and the seamless side wall.

The invention carries the nerve conduit equipment for directly writing 3D printing the inner wall micro-pattern, is suitable for various biological hydrogels, forms the nerve conduit with the inner wall micro-pattern (groove structure) in one step, and promotes the development of the structural design of the nerve conduit. The method gets rid of the defect of plane carving, and realizes the integrated design of materials, structures and functions by utilizing a direct writing type 3D printing system. The invention simplifies the complicated preparation process of the prior preparation method, is suitable for various biological hydrogels, reduces the production cost, is suitable for large-scale practical popularization of the nerve conduit with the inner wall micropatterned (groove structure), and has great application value.

Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.