CN111098489A

CN111098489A - Chitosan catheter and 3D printing device and printing method thereof

Info

Publication number: CN111098489A
Application number: CN201911358269.6A
Authority: CN
Inventors: 林锦新; 赵超前; 黄婷婷; 卢衍锦; 许泽亚
Original assignee: Fujian Institute of Research on the Structure of Matter of CAS
Current assignee: Fujian Institute of Research on the Structure of Matter of CAS
Priority date: 2019-12-25
Filing date: 2019-12-25
Publication date: 2020-05-05
Anticipated expiration: 2039-12-25
Also published as: CN111098489B

Abstract

The invention discloses a chitosan conduit, a 3D printing device and a printing method thereof. The chitosan slurry comprises: the chitosan-chitosan composite material comprises an acid solution and chitosan dissolved in the acid solution, wherein the acid solution is at least one of formic acid solution, acetic acid solution, lactic acid solution and glycolic acid solution, and the mass ratio of the chitosan to the acid solution is 1 (2-10). The catheter is 3D printed from chitosan slurry and optionally a support material, present or not. The catheter printing device includes at least one of a rotary module, a fused deposition module, and a freeze-drying module, optionally used in conjunction with an extrusion 3D printing formation module. The device and the printing method can select a 3D printing method to complete the preparation of the personalized and complex-structure catheter according to specific requirements.

Description

Chitosan catheter and 3D printing device and printing method thereof

Technical Field

The invention relates to the field of 3D printing, in particular to a chitosan catheter, a 3D printing device and a 3D printing method thereof.

Background

Ducts of human soft tissues, such as the trachea, blood vessels and pancreatic ducts, are of great importance in the transport of secretory, nutritional and metabolic waste products. If these sites are diseased, some biological material is needed to repair them. Synthetic polymers such as polysiloxanes, Polyurethanes (PU), Polyhydroxyalkanoates (PHA), and Polytetrafluoroethylene (PTFE) have been widely used to repair these tissues. Although these biomaterials have sufficient mechanical properties, biocompatibility and degradability limit their further applications. Soft tissue, where the mechanical properties (e.g., young's modulus) of degradable synthetic polymers such as polylactic acid (PLA), Polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) are not matched, may cause injury and inflammatory reactions in applications.

Chitosan (chitosan) is a natural polymer, the deacetylated form of chitin (> 50% deacetylation), the second most abundant biopolymer behind natural cellulose, obtained mainly from the exoskeleton of crustaceans. Chitosan is an excellent biocompatible polymer with a range of excellent properties, such as non-toxicity, biodegradability, antibacterial and immunomodulatory properties. Chitosan is a multifunctional material which is easy to prepare and can be used in the field of biomedicine. Chitosan and its derivatives can be designed for the manufacture of nanoparticles, fibers, fabrics, films, hydrogels, bandages and scaffolds for drug delivery, sutures, wound dressings, antimicrobial coatings, cell culture and tissue engineering. Generally, in dilute acids (pH <6.3), protonated free amino groups on glucosamine can be easily converted to amine groups, which will promote solubility of polymer molecules and provide a convenient method for preparing various forms. Chitosan is soluble in dilute aqueous solutions of acetic, lactic, malic, formic and succinic acids. However, chitosan is insoluble in solutions with pH values greater than 7, in crystalline form. The pH of the human environment, such as body fluids (pH 7.4), is alkaline, which determines that chitosan can be applied to most soft tissues.

Conventionally, the manufacturing method of the catheter mainly includes injection molding, freeze-drying, electrostatic spinning, and the like. These methods, while offering some solutions, have difficulty meeting personalization requirements. The tissue and organ of human body have great difference between different individuals, and the catheter has complicated shape and structure. Therefore, as medicine develops, personalized customization solutions are becoming more and more approved. The advent of 3D printing technology provides a great opportunity for the manufacture of personalized catheters. The 3D printing technology can prepare the catheter with a complex structure, accurate size and controllable shape. Currently, the mainstream 3D printing technology includes laser sintering/fusing technology, laser curing technology, inkjet printing technology, extrusion-based fused deposition manufacturing, ink direct-writing printing technology, and the like. Each material may be manufactured using a different 3D printing technique, and each 3D printing technique may also be suitable for the manufacture of different materials.

Disclosure of Invention

The present invention provides a chitosan slurry, comprising: the chitosan-chitosan composite material comprises an acid solution and chitosan dissolved in the acid solution, wherein the acid solution can be at least one selected from formic acid solution, acetic acid solution, lactic acid solution, glycolic acid solution and the like, and the mass ratio of the chitosan to the acid solution can be 1 (2-10), such as 1 (3-6), and exemplarily, the ratio is 1:3, 1:4, 1:5 or 1: 6.

According to an aspect of the invention, the concentration of the acid solution may be 10-80 wt%, such as 15-70 wt%, exemplified by 10 wt%, 30 wt%, 50 wt% or 70 wt%.

According to the technical scheme of the invention, the acid solution can be selected from a formic acid solution, an acetic acid solution, a lactic acid solution or a glycolic acid solution; the acid solution is preferably glycolic acid solution.

According to a preferred embodiment of the present invention, the chitosan slurry comprises: the mass ratio of the chitosan to the glycolic acid solution can be 1 (2-10), such as 1 (3-6), and exemplarily, the ratio is 1: 4; the glycolic acid solution has a concentration of 20 to 70 wt%, such as 25 to 50 wt%, with 30 wt% being exemplary.

The present invention also provides a chitosan slurry for use in the preparation of 3D printed catheters, said chitosan slurry having the meaning as described above.

The invention also provides application of the chitosan in preparing a (bionic) catheter by 3D printing.

The invention also provides application of the chitosan slurry in 3D preparation of (bionic) catheters. Preferably, the chitosan slurry comprises a glycolic acid solution and chitosan dissolved in the glycolic acid solution, and the mass ratio of the chitosan to the glycolic acid solution can be 1 (2-10).

The invention also provides a chitosan conduit, and the raw materials for preparing the chitosan conduit comprise the chitosan slurry and optional supporting materials which are present or not present. Preferably, the support material may be selected from degradable polymers, such as at least one of polylactic acid (PLA), Polycaprolactone (PCL), polyvinyl alcohol (PVA), and poly (lactic-co-glycolic acid) (PLGA), and the like, as well as PLA, PVA, or PLGA, illustratively PVA.

According to the technical scheme of the invention, the shape of the chitosan catheter is not limited, and the shape of the chitosan catheter can meet individual requirements so as to meet the shape of a tubular body used for repairing or connecting fractured or defective organism tissues; for example, the catheter may be a circular catheter having a simple structure, or may be a catheter having a complicated structure such as a Y-shape.

According to the technical scheme of the invention, the chitosan conduit can be provided with a circular conduit with the same or different wall thickness at different positions and/or the same or different inner diameter of each cross section. Further, the chitosan conduit may be composed of chitosan layers which are alternately stacked, or the conduit wall of the chitosan conduit may have a porous structure.

The invention also provides a printing device of the chitosan catheter, which comprises: a 3D printing platform, an extrusion 3D printing forming module, and optionally at least one of a rotation module, a fused deposition module, and a freeze drying module used in conjunction with the extrusion 3D printing forming module.

According to the technical scheme of the invention, the extrusion 3D printing and forming module, the fused deposition module, the rotating module and the freeze drying module can be designed into independent modules, the required modules are integrated together when the device is used, each module is communicated with the 3D printing platform, and the whole 3D printing process is controlled by using the same control system.

According to the technical scheme of the invention, the extrusion 3D printing and forming module can be an extrusion 3D printing and forming device known in the art, and for example, the extrusion 3D printing and forming module can comprise an extrusion unit which comprises a barrel, a piston, chitosan slurry positioned in the barrel, and a needle positioned at the bottom end of the barrel.

According to the technical scheme of the invention, the 3D printing platform is used for bearing a printing piece or supporting a rotating module.

According to an aspect of the present invention, the rotation module includes: a stepper motor and a rotating shaft driven by the stepper motor for supporting printing stock (i.e., chitosan slurry) deposited thereon. Further, the stepper motor may be placed on the printing platform.

According to the technical scheme of the invention, the fused deposition printing device known in the field can be selected as the fused deposition module, for example, the fused deposition printing device can comprise a coil, a polymer wound on the coil, a feeder and a heater, wherein the feeder is used for feeding the polymer wound on the coil into the heater. Wherein, the heater is used for holding the polymer after the melting, and the bottom of heater sets up the nozzle.

According to the technical scheme of the invention, the freeze drying module comprises a freeze dryer for drying the printed piece, and preferably also comprises a freezing box for primarily shaping the printed piece. Wherein the freezer (e.g., using compression refrigeration, or liquid nitrogen refrigeration) is disposed around the 3D printing platform; the freeze dryer can be one available in the market.

According to the technical scheme of the invention, the printing device optionally contains or does not contain a temperature control component, and the temperature control component can realize heating or cooling and is used for carrying out primary shaping on a printed piece. Preferably, the temperature control component is disposed around the 3D printing platform. Those skilled in the art will appreciate that the choice of heating means or cooling means may be further selected depending on the desired effect to be achieved. Wherein, heating device and heat sink can select the part known in the art for use, for example heating device can be electric heating cabinet, the heat sink can be the freezer.

According to an embodiment of the present invention, the printing apparatus of the chitosan catheter comprises: the device comprises an extrusion 3D printing and forming module, a rotating module integrated with the extrusion 3D printing and forming module and a 3D printing platform, wherein the rotating module comprises a stepping motor and a rotating shaft driven by the stepping motor, the stepping motor is placed on the 3D printing platform, and the rotating shaft is used for supporting chitosan slurry deposited on the rotating shaft; and the extrusion 3D printing and forming module and the rotating module are controlled by the same control system.

According to an embodiment of the present invention, the printing apparatus of the chitosan catheter comprises: and the extrusion 3D printing and molding module and the fused deposition module integrated with the same are controlled by the same control system.

According to an embodiment of the present invention, the printing apparatus of the chitosan catheter comprises: and the 3D extrusion printing and forming module and the freeze drying module integrated with the same are controlled by the same control system.

The invention also provides a preparation method of the chitosan catheter, which comprises the following steps: the chitosan conduit is prepared by using the chitosan slurry and the optional support material as printing raw materials and using the printing device.

According to the embodiment of the invention, when the extrusion 3D printing molding module and the rotating module integrated with the extrusion 3D printing molding module are adopted during preparation, chitosan slurry in the extrusion 3D printing molding module is extruded under the action of air pressure and is deposited on the rotating shaft; after printing was completed, the resulting printed sample was dried. Wherein the gas pressure is 0.4-1.0MPa, preferably 0.6-0.8MPa, exemplary 0.6MPa, 0.7MPa or 0.8 MPa. Wherein the movement speed of the rotating module (i.e. the linear speed of the rotating shaft) is 1-10mm/s, preferably 3-5mm/s, exemplary 3mm/s, 4mm/s or 5 mm/s. Wherein the speed of movement of the extrusion module (speed of movement along a horizontal plane, i.e. the speed of movement of the needle) is 0.05-0.3mm/s, such as 0.08-0.28mm/s, exemplary 0.08mm/s, 0.10mm/s, 0.12mm/s, 0.14mm/s, 0.18mm/s, 0.20mm/s, 0.25 mm/s. Wherein the extrusion speed of the chitosan slurry is 1-10mm/s, preferably 3-5mm/s, exemplary 3mm/s, 4mm/s or 5 mm/s. Wherein the chitosan slurry after extrusion has a diameter of 0.2-0.6mm, such as 0.3-0.5mm, exemplary 0.4 mm. Wherein the diameter of the rotation axis is 1-3mm, such as 1.5-2.5mm, exemplary 2 mm. Wherein the rotational speed of the rotating shaft may be 0.15-0.8, such as 0.2-0.7, exemplary 0.21, 0.24, 0.29, 0.35, 0.45, 0.64. Wherein the rotation axis rotates for a period of 1-6s, such as 1.5-5s, exemplary 1.57s, 2.20s, 2.83s, 3.46s, 4.08s, 4.71 s. The print layer has a thickness of 0.1 to 0.5mm, preferably 0.2 to 0.4mm, and exemplary 0.3 mm. Wherein the chitosan slurry is deposited in at least one layer, such as at least two, three or more layers.

According to an embodiment of the present invention, when an extrusion 3D printing molding module and a fused deposition module integrated therewith are used for the preparation, the preparation process of the chitosan catheter comprises the following steps: (1) extruding chitosan slurry in the extrusion 3D printing and forming module under the action of air pressure, and depositing a chitosan layer; (2) after being heated and melted, the support material is extruded from a heater and is used for depositing a support material layer; (3) under the control of a program, firstly, printing of a layer of supporting material layer is completed, then, printing of a layer of chitosan layer is completed, the process is circulated and repeated until the 3D printing process is completed, and the obtained printing sample is dried. Wherein the gas pressure is 0.4-1.0MPa, preferably 0.6-0.8MPa, exemplary 0.6MPa, 0.7MPa or 0.8 MPa. Wherein, the movement speed of the extrusion 3D printing and molding module and the fused deposition module can be 1-10mm/s, preferably 3-5mm/s, and is exemplarily 3mm/s, 4mm/s or 5 mm/s. Wherein the support material has the meaning as described above. The print layer has a thickness of 0.1 to 0.5mm, preferably 0.2 to 0.4mm, and exemplary 0.3 mm. Wherein the extruded chitosan filaments and the support material filaments may have the same or different diameters, preferably the same diameter, e.g. between 0.2 and 0.6mm, and the same diameter; exemplary diameters are all 0.4 mm.

According to the technical scheme of the invention, when the 3D extrusion printing forming module and the freeze drying module integrated with the same are adopted, chitosan slurry in the 3D extrusion printing forming module is extruded under the action of air pressure and deposited on a printing platform, and the slurry is quickly solidified and formed under the action of low temperature; the shaped sample was then lyophilized.

According to the technical scheme of the invention, the low temperature is only needed to enable sizing of the slurry, and the temperature is-50 to-30 ℃, for example-50 ℃. Wherein the temperature of the lyophilization is from-60 to-40 ℃, such as from-55 to-45 ℃, exemplary-50 ℃. The printed chitosan conduit can be quickly frozen to dehydrate the conduit for forming.

According to the technical scheme of the invention, the method further comprises a post-treatment process of the dried printing piece, for example, the printing piece is sequentially subjected to alkali treatment and water soaking to remove impurities, such as acid solution in chitosan slurry, excessive alkali in the alkali treatment, salt generated by the alkali and the acid and/or supporting materials. Wherein, the alkali treatment adopts a mixed solution of alkali, water and ethanol, for example, the molar ratio of the alkali, the water and the ethanol in the mixed solution is 1 (4-8) to (2-4), preferably 1 (5-7) to (2.5-3.5), and exemplarily 1:6: 3. Among them, the water is preferably pure water. Further, when the impurities are removed by soaking with water, the water temperature needs to be a temperature capable of dissolving the impurities, preferably a temperature capable of dissolving the salt of the alkali with the acid and/or the support material.

The invention also provides the application of the chitosan catheter as a bionic catheter.

The bionic duct and the duct have the same meanings, refer to a tubular body used for repairing or connecting broken or defected organism tissues, can replace the original organism tissue duct to play a role, can be degraded and can induce the regeneration of the tissue duct, and are used for repairing soft tissues such as nerve ducts, blood vessels, pancreatic ducts, bile ducts and the like. In one embodiment, nerve cell regeneration can be guided and promoted by sleeving both ends of a defective or severed nerve into the lumen of a catheter. In one embodiment, a catheter is introduced during pancreaticostomy, which conducts pancreatic juice into the intestine, acting as a pancreatic duct.

The invention has the beneficial effects that:

1. the invention selects different acids, acid solutions with different concentrations and different proportions with chitosan to prepare chitosan slurry. The chitosan slurry can be used for preparing catheters, particularly chitosan slurry containing glycolic acid has excellent biocompatibility, and can be used for preparing catheters meeting requirements of soft tissue or nerve repair.

2. The conventional mode is difficult to prepare the catheter with a complex structure and individuation, and the invention combines an extrusion 3D printing method with other modes, such as rotating shaft deposition, fused deposition and freeze drying, so that the catheter with different structures and individuation can be prepared according to actual requirements.

3. Extrusion 3D printing modeling, rotating shafts, fused deposition fabrication, and freeze-drying, can all be achieved by separate modules. When the device is used, the required modules are integrated, so that the convenience of operation is greatly improved.

4. The chitosan catheter prepared by the method has good biocompatibility and excellent mechanical property, and can meet the requirements of soft tissue repair.

Drawings

Fig. 1 is a schematic diagram of the combination of an extrusion 3D printing and molding module and a rotation module in embodiment 1.

Fig. 2 is a schematic diagram of a movement relationship between the combination of the extrusion 3D printing and molding module and the rotation module in embodiment 1.

Fig. 3 is a schematic structural diagram of the combination of the extrusion 3D printing and molding module and the fused deposition module in example 2.

Fig. 4 is a schematic structural diagram of the combination of extrusion 3D printing and forming and freeze drying module in example 4.

Fig. 5 is a structure diagram of a multi-module integrated 3D printing in embodiment 5.

Fig. 6 is a view showing a chitosan catheter of a simple structure prepared by combining an extrusion 3D printing molding module and a rotation module in example 1.

Fig. 7 is a complex-structured chitosan catheter prepared by combining the extrusion 3D printing molding module and the fused deposition module in example 2.

The reference numerals shown in figures 1-5 are as follows: 1-1-gas inlet, 1-2-piston, 1-3-material cylinder, 1-4-chitosan slurry, 1-5-material cylinder needle, 1-6-stepping motor, 1-7-rotating shaft, 1-8-3D printing platform, 1-9-alkali solution system and 1-10-pure water;

3-1-nozzle, 3-2-heater, 3-3-feeder, 3-4-PVA wire, 3-5-PVA coil;

4-1-freezer;

5-1-fused deposition module, 5-2-extrusion 3D printing module, and 5-3-rotation module.

Detailed Description

The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.

Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.

Example 1

[ preparation of Chitosan slurry ]

Different acids and acid solutions with different mass concentrations are selected to prepare chitosan slurry, and the details are shown in the following table 1.

The properties of the chitosan slurries prepared according to the proportions in table 1 were tested:

tensile strength was tested according to GB/T1040-2006;

cytotoxicity was tested according to ISO 10993-52016, in which the cells used for the test were mouse fibroblasts (L-929, supplied by cell Bank, national academy of sciences). Cell viability > 70% indicates no potential cytotoxicity.

TABLE 1 preparation of Chitosan slurries

As can be seen from table 1, the chitosan slurry containing glycolic acid (mass concentration of glycolic acid 30 wt.%, mass ratio of chitosan to acid solution 1:4) has no potential cytotoxicity. This was used as a printing stock in examples 2 to 4 described below. Embodiment 2 printing device and method combining extrusion 3D printing module and rotation module

In the printing apparatus shown in fig. 1, an extrusion 3D printing module is combined with a rotation module for preparing a chitosan catheter of a simple structure. The extrusion 3D printing module comprises a gas inlet 1-1, a piston 1-2, a material cylinder 1-3 and a needle 1-5, wherein chitosan slurry 1-4 is contained in the material cylinder 1-3. The rotating module comprises stepping motors 1-6 and rotating shafts 1-7 driven by the stepping motors 1-6, the rotating shafts 1-7 are used for supporting the chitosan slurry deposited on the rotating shafts 1-7, and the stepping motors 1-6 are placed on the 3D printing platform 1-8. The printing process comprises the following steps:

the pressure is transmitted to the chitosan slurry through the piston 1-2 under the action of the pressure of the gas introduced into the gas inlet 1-1, and the slurry is extruded from the needle 1-5.

Under the control of a program, 1-6 stepping motors drive 1-7 rotating shafts to rotate, so that the chitosan slurry is deposited on the rotating shafts.

The moving speed of the rotating module is 4mm/s, and the air pressure is 0.6 MPa. The print layer thickness was 0.4 mm.

After the printing process was completed, the detachable part of the rotating shaft with the print was removed and placed in an environment of 70 ℃ for drying for 4 hours.

The printed catheter was then removed from the rotating shaft and placed in an alkaline solution system 1-9 (molar ratio 1:6:3) consisting of potassium hydroxide-water-ethanol to remove the acid solution.

Subsequently, the catheter was placed in pure water 1 to 10, and excess potassium hydroxide and a salt formed from glycolic acid and potassium hydroxide were removed.

Printing resulted in a simple structured chitosan catheter, which was a circular catheter of unequal thickness, as shown in fig. 6.

The rotating module and the extrusion 3D printing module need to satisfy the following relationship to ensure the precise unity of the two modules in the printing process, as shown in fig. 2 and table 2.

The rotational linear velocity of the rotating shaft or the extrusion speed can be derived from equation (1),

the rotational speed of the rotating shaft can be derived from (1),

the time taken for the rotating shaft to rotate one revolution can be obtained,

the speed of movement of the extrusion 3D printing module is,

wherein the content of the first and second substances,

v_extrusionis the extrusion rate of chitosan;

n_axisis the rotational speed of the rotating shaft;

d_CSthe extruded size of the chitosan;

v_syringethe moving speed of the needle head;

d_axisthe diameter of the rotating shaft;

t₁the time taken for one revolution;

m number of layers of chitosan printing.

TABLE 2 implementation data of the relevant parameters

v_syringe(mm/s)	m	v_extrusion(mm/s)	d_axis(mm)	d_CS(mm)	n_axis	t₁(s)
							0.25	0	4.00	2.00	0.40	0.64	1.57
0.18	1	4.00	2.00	0.40	0.45	2.20
							0.14	2	4.00	2.00	0.40	0.35	2.83
0.12	3	4.00	2.00	0.40	0.29	3.46
							0.10	4	4.00	2.00	0.40	0.24	4.08
0.08	5	4.00	2.00	0.40	0.21	4.71

Embodiment 3 printing device and printing method combining extrusion 3D printing module and fused deposition module

An extrusion 3D printing module was combined with a fused deposition module as shown in fig. 3 for the preparation of chitosan catheters of complex structure.

The structure of the extrusion 3D printing module was the same as in example 2, and the fused deposition module included PVA coils 3-5, PVA wires 3-4 wound on the PVA coils 3-5, a feeder 3-3, a heater 3-2, and a nozzle 3-1. The printing process comprises the following steps:

under program control, the feeder 3-3 passes the PVA wire 3-4 in the PVA coil 3-5 to the heater 3-2. The PVA thread is melted and extruded through the nozzle 3-1 under pressure provided by the feeder 3-3.

The extrusion 3D printing module and the fused deposition module are both under the same program control. Under the control of the program, the manufacture of a layer of PVA is firstly completed, and then the manufacture of a layer of chitosan is completed. And then finishing a layer of PVA manufacturing, and circulating and reciprocating until finishing the 3D printing process.

The movement speed of the extrusion 3D printing module and the fused deposition module was 4 mm/s. The air pressure is 0.6 MPa. The print layer thickness was 0.4 mm.

After the printing process was completed, the printed sample was placed in an environment of 70 ℃ for drying for 4 hours.

The printed sample was then placed in a system consisting of potassium hydroxide-water-ethanol 1-9 (molar ratio 1:6:3) and the acid solution was removed.

Next, the print sample was put in pure water 1 to 10 (water temperature 25 ℃ C.) to remove PVA, excess potassium hydroxide, and a salt formed by glycolic acid and potassium hydroxide.

The printed chitosan catheter with a complex structure is shown in fig. 7.

Example 4 printing apparatus and printing method combining an extrusion 3D printing module with a freeze-drying module

The extrusion 3D printing module was combined with a freeze drying module as shown in fig. 4 for the preparation of chitosan catheters of complex structure. The structure of the extrusion 3D printing module is the same as that of embodiment 2, the freeze drying module comprises a freezing box 4-1 and a freeze dryer (not shown in the figure), the freezing box 4-1 is used for primarily shaping a printed piece in the printing process, and the freezing box 4-1 surrounds the 3D printing platform 1-8. The extrusion 3D printing module and the freeze drying module are both under the same program control.

The printing method comprises the following steps:

under program control, the extrusion 3D printing module forms a layer of chitosan slurry onto the 3D printing platform 1-8. Since the 3D printing platforms 1-8 are in the freezing module, the liquid water contained in the slurry falling on the printing platform quickly freezes and becomes fixed. And then manufacturing the next chitosan layer until the 3D printing process is completed.

The movement speed of the extrusion 3D printing module is 4mm/s, and the air pressure is 0.6 MPa. The print layer thickness was 0.4 mm.

The temperature of the freezer of the freeze drying module was-50 ℃. After the printing process was completed, the sample was placed in a freeze dryer at a temperature of-50 ℃ and a pressure of 20 Pa.

The printed sample was then placed in 1-10 pure water to remove excess potassium hydroxide, as well as glycolic acid and potassium hydroxide forming salts.

Embodiment 5 multimode integrated 3D printing device

Fig. 5 is a structural diagram of a multi-module integrated 3D printing apparatus. The device mainly comprises a fused deposition module 5-1, an extrusion 3D printing module 5-2, a freezing box 4-1, a rotating module 5-3 and a 3D printing platform 1-8.

Wherein, the fused deposition module 5-1 and the extrusion 3D printing module 5-2 are fixed on a moving mechanism for 3D printing. The freezer 4-1 is disposed around the 3D printing platform 1-8. The rotating module 5-3 is located on the 3D printing platform 1-8 and inside the freezer 4-1.

The modules are controlled by the same set of control program, and different combinations are selected according to requirements to meet different requirements.

The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A chitosan slurry, wherein said chitosan slurry comprises: the chitosan-chitosan composite material comprises an acid solution and chitosan dissolved in the acid solution, wherein the acid solution is at least one of a formic acid solution, an acetic acid solution, a lactic acid solution and a glycolic acid solution, and the mass ratio of the chitosan to the acid solution is 1 (2-10).

2. The chitosan slurry of claim 1, wherein the acid solution has a concentration of 10-80 wt%;

preferably, the acid solution is selected from a formic acid solution, an acetic acid solution, a lactic acid solution or a glycolic acid solution; the acid solution is preferably glycolic acid solution;

preferably, the chitosan slurry comprises: the chitosan-chitosan composite material comprises an glycolic acid solution and chitosan dissolved in the glycolic acid solution, wherein the mass ratio of the chitosan to the glycolic acid solution is 1 (2-10), and the concentration of the glycolic acid solution is 20-70 wt%.

3. A chitosan slurry for the preparation of 3D printed catheters, characterized in that it has the meaning as described in claim 1 or 2.

4. Application of chitosan in 3D printing preparation of a bionic catheter.

5. Use of the chitosan slurry of claim 1 or 2 for 3D preparation of a biomimetic catheter.

6. A chitosan conduit, wherein the raw material for preparing the chitosan conduit comprises the chitosan slurry of claim 1 or 2, and optionally the support material, or not;

preferably, the support material is selected from degradable polymers, preferably at least one of polylactic acid, polycaprolactone, polyvinyl alcohol and polylactic acid-glycolic acid copolymer;

preferably, the shape of the chitosan conduit is not limited, and the shape of the chitosan conduit meets the personalized requirements.

7. Printing apparatus useful for preparing the chitosan catheter of claim 6, wherein the apparatus comprises: a 3D printing platform, an extrusion 3D printing forming module, and optionally at least one of a rotation module, a fused deposition module, and a freeze drying module used in conjunction with the extrusion 3D printing forming module;

preferably, the extrusion 3D printing and molding module comprises an extrusion unit including a barrel, a piston, chitosan slurry in the barrel, and a needle at the bottom end of the barrel;

preferably, the 3D printing platform is used to carry prints or support a rotating module;

preferably, the rotation module includes: a stepping motor and a rotating shaft driven by the stepping motor, the rotating shaft for supporting printing material deposited thereon; the stepping motor is placed on the printing platform;

preferably, the fused deposition module comprises a coil, a polymer wound on the coil, a feeder and a heater, wherein the feeder is used for feeding the polymer wound on the coil into the heater, the heater is used for accommodating the melted polymer, and a nozzle is arranged at the bottom end of the heater;

preferably, the freeze drying module comprises a freeze dryer for drying the print, and preferably further comprises a freezer for preliminary sizing the print; the freezer is arranged around the 3D printing platform;

preferably, the printing device optionally further comprises or does not comprise a temperature control component, and the temperature control component can realize heating or cooling and is used for carrying out primary shaping on a printed piece.

8. The printing device of claim 7, wherein the chitosan catheter printing device comprises: the device comprises an extrusion 3D printing and forming module, a rotating module integrated with the extrusion 3D printing and forming module and a 3D printing platform, wherein the rotating module comprises a stepping motor and a rotating shaft driven by the stepping motor, the stepping motor is placed on the 3D printing platform, and the rotating shaft is used for supporting chitosan slurry deposited on the rotating shaft; the extrusion 3D printing and forming module and the rotating module are controlled by the same control system;

alternatively, the printing device of the chitosan catheter comprises: the 3D printing and forming module and the fused deposition module integrated with the module are extruded and controlled by the same control system;

alternatively, the printing device of the chitosan catheter comprises: and the 3D extrusion printing and forming module and the freeze drying module integrated with the same are controlled by the same control system.

9. The method of making the chitosan catheter of claim 6, comprising the steps of: the chitosan catheter is prepared by using the printing apparatus of claim 7 or 8, with the chitosan slurry and optionally the support material present or absent as printing raw materials.

10. The preparation method according to claim 9, wherein when the extrusion 3D printing molding module and the rotating module integrated therewith are used for preparation, the chitosan slurry in the extrusion 3D printing molding module is extruded under the action of air pressure to be deposited on the rotating shaft; after printing is finished, drying the obtained printing sample;

preferably, when an extrusion 3D printing molding module and a fused deposition module integrated with the same are adopted in the preparation process, the preparation process of the chitosan conduit comprises the following steps: (1) extruding chitosan slurry in the extrusion 3D printing and forming module under the action of air pressure, and depositing a chitosan layer; (2) after being heated and melted, the support material is extruded from a heater and is used for depositing a support material layer; (3) under the control of a program, firstly, printing a layer of supporting material layer, then, printing a layer of chitosan layer, and repeating the steps until the 3D printing process is completed, and drying the obtained printed sample;

preferably, when the extrusion 3D printing and forming module and the freeze drying module integrated with the extrusion 3D printing and forming module are adopted, chitosan slurry in the extrusion 3D printing and forming module is extruded under the action of air pressure and is deposited on the printing platform, and the slurry is quickly solidified and formed under the action of low temperature; then freeze-drying the formed sample;

preferably, the method further comprises a post-treatment process of the dried print.