KR102665324B1 - Composite material for 3d printing, manufacturing method thereof, and 3d printed stent comprising the same - Google Patents

Abstract

One embodiment of the present invention is a biodegradable polymer resin; and tantalum oxide dispersed in the biodegradable polymer resin. It provides a composite material for 3D printing, characterized by improved mechanical properties and biocompatibility.
According to the above configuration, problems such as restenosis that occur in stents manufactured using conventional metals can be solved, and the limitations of mechanical properties seen by stents manufactured only with conventional polymer resins can be solved. It can overcome and solve the poor biocompatibility due to the hydrophobicity of the polymer.

Description

Composite material for 3D printing, manufacturing method thereof, and 3D printed stent containing the same {COMPOSITE MATERIAL FOR 3D PRINTING, MANUFACTURING METHOD THEREOF, AND 3D PRINTED STENT COMPRISING THE SAME}

The present invention relates to a composite material for 3D printing, and more specifically, to a composite material for 3D printing containing a biodegradable polymer resin and tantalum oxide, a manufacturing method thereof, and a 3D printed stent manufactured including the same.

Various attempts are underway to apply 3D printing technology to medical device manufacturing. In that medical devices must be modified in shape and structure to suit the patient, existing molding technology has limitations in both performance and economic feasibility, while 3D printing technology allows for a variety of customized designs based on the patient's measured physical information and This is because it is suitable for implementing complex shapes according to the structure.

In order to manufacture medical devices using 3D printing technology, selecting an appropriate filament material is most important. Physical properties such as elasticity and rigidity that can implement and maintain the desired shape must be satisfied, and additional conditions that take into account the special characteristics of being used in the body, such as biocompatibility and biodegradability, are required.

The purpose of the present invention is to manufacture a medical stent that can be used for cardiovascular disease using 3D printing technology, and to develop a suitable composite material for 3D printing.

Looking at the materials that have been used to manufacture medical stents using 3D printing technology, they are largely metals and polymers. Stents manufactured using metal have the advantage of having sufficient physical properties, but there is a problem that they remain in the body without being decomposed and subsequently leave scars on the affected area or cause restenosis. In addition, stents manufactured using polymers showed limitations in mechanical properties, and the mainstream polymer materials were hydrophobic and showed poor biocompatibility.

Looking at prior literature published from this perspective, Korea Patent Publication No. 10-2019-0109613 (name: 3D printing filament) is an extrusion-laminated 3D printing filament with excellent biocompatibility, harmless to the human body and the environment, and strong. A filament core formed from a filament resin composition containing a biocompatible resin for the purpose of providing a filament for 3D printing that is excellent and highly usable; and a 3D printing filament comprising a coating layer formed on the surface of the core and formed from a coating composition containing a chain extender, and an epoxy-based reactive oligomer is adopted as a material constituting the chain extender. However, since the composition disclosed in the preceding literature is composed of a polymer complex, it can be seen that there are limitations in completely overcoming the poor biocompatibility due to the hydrophobicity of the polymer described above.

Therefore, research on materials with sufficient physical properties and excellent biocompatibility is still urgent.

Republic of Korea Patent Publication No. 10-2019-0109613

The purpose of the present invention was created to solve and improve the problems of the prior art as described above, and to provide a composite material for 3D printing in which bio-ceramic nanoparticles are dispersed in a biodegradable polymer to have sufficient physical properties and excellent biocompatibility. To provide a manufacturing method and a stent manufactured using 3D printing including the same.

The technical problem to be achieved by the present invention is not limited to the technical problem mentioned above, and other technical problems not mentioned can be clearly understood by those skilled in the art from the description below. There will be.

In one embodiment of the present invention to achieve the above technical problem, the composite material for 3D printing includes a biodegradable polymer resin; and tantalum oxide dispersed in the biodegradable polymer resin.

In an embodiment of the present invention, the biodegradable polymer resin is polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, poly-l-lactic acid, poly(lactic-co-glycolic acid), glycolide- It may include any one or more selected from the group consisting of co-trimethylene carbonate, glycolide-co-ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof.

In an embodiment of the present invention, the biodegradable polymer resin may have a number average molecular weight of 40,000 or more and 50,000 or less.

In an embodiment of the present invention, the tantalum oxide may be included in an amount of 1 wt% or more and 5 wt% or less based on the total weight of the 3D printing composite material.

In an embodiment of the present invention, the tantalum oxide may have an average particle size of 50 nm or more and 80 nm or less.

In an embodiment of the present invention, the tantalum oxide may be tantalum pentoxide (Ta ₂ O ₅ ).

A method of manufacturing a composite material for 3D printing, which is another embodiment of the present invention for achieving the above technical problem, includes the steps of i) producing a sol containing tantalum oxide; ii) mixing the biodegradable polymer resin and the sol in a solvent.

In an embodiment of the present invention, the step of preparing the sol includes a) mixing a tantalum precursor, an organic solvent, distilled water, and an acid; b) dispersing the mixture of step a) above.

In an embodiment of the present invention, the tantalum precursor includes at least one selected from the group consisting of tantalum(V) ethoxide, tantalum(V) chloride, and combinations thereof, and the organic solvent includes isopropyl alcohol, ethanol, and It may include at least one selected from the group consisting of combinations thereof, and the acid may include at least one selected from the group consisting of hydrochloric acid, nitric acid, acetic acid, and combinations thereof.

In an embodiment of the present invention, the solvent in step ii) includes dichloromethane, and the biodegradable polymer resin includes polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, and poly-l-lactic acid. , poly(lactic-co-glycolic acid), glycolide-co-trimethylene carbonate, glycolide-co-ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof. It can be included.

In an embodiment of the present invention, the biodegradable polymer resin of step ii) may have a number average molecular weight of 40,000 or more and 50,000 or less.

A 3D printed stent, which is another embodiment of the present invention for achieving the above technical problem, is characterized by being manufactured by a 3D printing method using the above 3D printing composite material.

In an embodiment of the present invention, an immunosuppressant coated on the surface of the 3D printed stent may be further included.

In an embodiment of the present invention, the immunosuppressant may include one or more selected from the group consisting of sirolimus, Paclitaxel, and combinations thereof.

The effect of the present invention according to the above configuration is,

Since biodegradable polymer resin is used, problems such as restenosis that occur in stents manufactured using conventional metals can be solved.

By including bio-ceramic nanoparticles with excellent mechanical properties and high biocompatibility, it is possible to overcome the limitations in mechanical properties of stents made only from conventional polymer resins and solve the poor biocompatibility due to the hydrophobicity of the polymer.

In addition, the manufacturing method provided by the present invention evenly disperses the bio-ceramic nanoparticles on the biodegradable polymer resin, so the stent manufactured using this has physical properties including the advantages of the bio-ceramic nanoparticles described above. It appears uniform.

The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

Figure 1 is a 3D modeling image of a 3D printed stent, which is an embodiment of the present invention, and is partially enlarged to show the form in which the stent combines with cells and the extrusion of the composite material for 3D printing that makes up the stent. This is an image showing the molded form.
Figure 2 is a flowchart showing a method of manufacturing a composite material for 3D printing, which is an embodiment of the present invention.
Figure 3 is an image showing an example of an immunosuppressant being coated on a 3D printed stent, which is an embodiment of the present invention.
Figure 4 is an image of a pellet manufactured from a composite material with different contents of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.
Figure 5 is DLS analysis data of a tantalum pentoxide solution in a method of manufacturing a composite material for 3D printing, which is an embodiment of the present invention.
Figure 6 is TGA analysis data of a composite material for 3D printing, which is an embodiment of the present invention, with different contents of tantalum pentoxide.
Figure 7 is DSC analysis data of a composite material with different contents of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.
Figure 8 shows tensile strength analysis data performed using composite materials with different amounts of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.
Figure 9 shows compressive strength analysis data performed using composite materials with different amounts of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.
Figure 10 shows the results of a cell adhesion experiment performed using composite materials with different contents of tantalum pentoxide in the composite material for 3D printing, which is an embodiment of the present invention.
Figure 11 is an image of a 3D printed stent printed using a composite material with different contents of tantalum pentoxide in the composite material for 3D printing, which is an embodiment of the present invention.
Figure 12 is (a) an image of a 3D printed stent manufactured using a composite material containing 5 wt% of tantalum pentoxide based on the total weight in the composite material for 3D printing, which is an embodiment of the present invention, (b), (c) are its SEM images, and (d) are its EDX analysis images.
Figure 13 shows data measuring drug release behavior when an immunosuppressant is coated on a 3D printed stent, which is an embodiment of the present invention.

Hereinafter, the present invention will be described with reference to the attached drawings. However, the present invention may be implemented in various different forms and, therefore, is not limited to the embodiments described herein. In order to clearly explain the present invention in the drawings, parts unrelated to the description are omitted, and similar parts are given similar reference numerals throughout the specification.

Throughout the specification, when a part is said to be "connected (connected, contacted, combined)" with another part, this means not only "directly connected" but also "indirectly connected" with another member in between. "Includes cases where it is. Additionally, when a part is said to “include” a certain component, this does not mean that other components are excluded, but that other components can be added, unless specifically stated to the contrary.

The terms used in this specification are merely used to describe specific embodiments and are not intended to limit the invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this specification, terms such as “comprise” or “have” are intended to designate the presence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, but are not intended to indicate the presence of one or more other features. It should be understood that this does not exclude in advance the possibility of the existence or addition of elements, numbers, steps, operations, components, parts, or combinations thereof.

In this specification, “biodegradable” is a word corresponding to biodegradable in English and means that the material decomposes in the natural environment through microorganisms, etc., and in the present invention related to medical devices that can be inserted into the living body, it especially refers to biodegradable It can be understood to mean a substance that can be naturally decomposed in the environment without any additional treatment.

In this specification, “nanoparticles” refers to fine particles and can be understood to mean particles having nano or micro units. Although the expression nano is used, the unit does not necessarily mean only particles in the nm unit, and should be understood to mean fine particles containing tantalum oxide dispersed in a biodegradable polymer resin.

Hereinafter, the composite material 10 for 3D printing, which is an embodiment of the present invention, will be described in detail with reference to the attached drawings.

The composite material 10 for 3D printing, which is an embodiment of the present invention, includes a biodegradable polymer resin 100; and tantalum oxide 200 dispersed in the biodegradable polymer resin 100, and is characterized by improved mechanical properties and biocompatibility.

Prior to a detailed description of each configuration, let us look at the characteristics of the composite material 10 for 3D printing according to the above configuration.

The composite material 10 for 3D printing is a composite material in which a biodegradable polymer resin 100 and tantalum oxide 200 are dispersed.

Since biodegradable polymer resin 100 is used, medical devices such as stents manufactured using the 3D printing composite material 10 decompose after a certain period of time even when inserted into the body. Therefore, there is no concern about side effects caused by medical devices manufactured from previously non-biodegradable materials remaining in the body.

Based on these advantages, various biodegradable materials are widely used in biomaterials research. However, most of the biodegradable polymers that have been widely studied and used conventionally show limitations in mechanical properties, and due to their hydrophobic surfaces, they have low affinity to cells, which limits initial adhesion to cells when inserted into the body.

To solve this problem, the present invention attempted to disperse tantalum oxide 200, which is classified as a bioceramic and has particularly excellent biocompatibility, into the biodegradable polymer resin 100 in the form of nanoparticles.

The tantalum oxide 200 evenly dispersed in the biodegradable polymer resin 100 complements the physical properties such as tensile strength and compressive strength of the biodegradable polymer resin 100 with excellent mechanical properties compared to the polymer, and is especially effective in biodegradable polymer resin ( The tantalum oxide 200 dispersed on the surface of the biodegradable polymer resin 100 modifies the hydrophobic surface characteristics of the biodegradable polymer resin 100 to improve affinity with biological cells.

Accordingly, the present invention has the advantage that (1) even if inserted into the living body, it is naturally decomposed or discharged, so there are no residual problems, (2) it has sufficient mechanical properties to withstand or support the movement of the living body, and it also contains tantalum oxide ( 200) has the advantage of being able to adjust the mechanical properties according to the desired environment by changing the content, and (3) is a composite material for 3D printing that has the advantage of excellent affinity with biological cells by improving the hydrophobic surface characteristics of the polymer resin (10). ) and a 3D printed stent (20) manufactured using it can be provided.

Below, we will look at each configuration in detail.

First, the biodegradable polymer resin 100 will be described.

Referring to Figure 1, the biodegradable polymer resin 100 serves as a matrix in the composite material 10 for 3D printing. Specifically, since the tantalum oxide 200 alone cannot produce a molded product, the biodegradable polymer resin 100, which has a low melting point and is easy to mold, serves as a matrix.

Materials constituting the biodegradable polymer resin 100 include polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, poly-l-lactic acid, poly(lactic-co-glycolic acid), glycolide- It may include any one or more selected from the group consisting of co-trimethylene carbonate, glycolide-co-ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof.

However, it is not limited thereto, and any material that is biodegradable and has moldability with a low melting point can be used as a matrix material of the present invention.

Preferably, PCL (polycaprolactone) can be used as a material constituting the biodegradable polymer resin 100, which has excellent ductility, excellent moldability at low temperatures, and a decomposition period suitable for biological procedures, This is because it has high solubility in organic solvents compared to other polymers and blends stably with other materials.

At this time, the biodegradable polymer resin 100 may have a number average molecular weight of 40,000 or more and 50,000 or less.

Specifically, the biodegradable polymer resin 100 becomes harder as its number average molecular weight increases, but at the same time shows the characteristic of becoming more brittle. In addition, the inorganic nanoparticles mixed with the biodegradable polymer resin 100 modify the properties of the composite material 10 according to the inherent properties of the material, but at the same time increase the brittleness of the composite material.

Therefore, in the 3D printing composite material 10 containing the biodegradable polymer resin 100 and tantalum oxide 200, the number average molecular weight of the biodegradable polymer resin 100 and that of the tantalum oxide 200 are determined in consideration of brittleness. Controlling the content can be said to be very important.

To be more specific, based on an experimental example conducted in the present invention, if the number average molecular weight of the biodegradable polymer resin 100 is less than 16,000, brittleness due to the biodegradable polymer resin 100 is not a problem, but the small number average molecular weight Due to this, it does not have sufficient mechanical properties, and even if tantalum oxide 200 is additionally included, there is a problem in that excessive tantalum oxide 200 is not uniformly distributed when synthesizing the composite material 10 for 3D printing.

On the other hand, when the number average molecular weight of the biodegradable polymer resin (100) exceeds 80000, the content of tantalum oxide (200) that can be included in consideration of brittleness is reduced, thereby achieving the effect of improving biocompatibility for which the present invention aims. Can not.

Therefore, considering brittleness, the output characteristics of the 3D printing composite material 10, and the physical properties required for the stent that the present invention is to manufacture using the 3D printing composite material 10, in the present invention The number average molecular weight of the biodegradable polymer resin 100 is preferably 40,000 to 50,000.

Next, the tantalum oxide 200 dispersed in the biodegradable polymer resin 100 will be described.

The tantalum oxide 200 is evenly dispersed in the biodegradable polymer resin 100. Specifically, the tantalum oxide 200 is evenly distributed throughout the biodegradable polymer resin 100, including the surface and interior, to complement the mechanical properties.

As the tantalum oxide 200 is included, the tensile strength and compressive strength of the 3D printing composite material 10 and the 3D printing stent 20 containing it increase, thereby improving mechanical properties. Accordingly, it is possible to manufacture a stent with the desired diameter, elasticity, strength, and expandability at a thinner thickness.

According to what is known, the reason why stents made of biodegradable materials do not sufficiently replace stents made using existing metals is that the thickness of the stents made of biodegradable materials is not thin enough, Stents that are not thin enough have a higher rate of thrombosis than thin metal stents and are said to be vulnerable to various cardiovascular problems.

Considering this, the composite material 10 for 3D printing proposed in the present invention has the advantage of being biodegradable, and at the same time, by containing tantalum oxide (200) nanoparticles, it is possible to manufacture thin-walled stents, so it is very flexible. It can be said to be encouraging.

Next, tantalum oxide 200 is dispersed on the surface of the biodegradable polymer resin 100 to modify the hydrophobic surface characteristics of the biodegradable polymer.

Specifically, due to the high biocompatibility of tantalum oxide (200) itself, the biocompatibility and wettability of the 3D printing composite material (10) containing it are improved, and at the same time, it is evenly distributed on the surface of the biodegradable polymer resin (100). Since the tantalum oxide (200) nanoparticles replace the surface of the hydrophobic biodegradable polymer resin (100), the overall biocompatibility of the 3D printing composite material (10) containing it is very excellent.

Accordingly, a stent manufactured using the 3D printing composite material 10 proposed by the present invention has sufficient bonding force to be inserted into the body and not be initially positioned or fall off from the existing position.

At this time, the tantalum oxide 200 may be included in an amount of 1 wt% or more and 5 wt% or less based on the total weight of the 3D printing composite material 10.

Specifically, when the tantalum oxide 200 is included in less than 1 wt% based on the total weight of the 3D printing composite material 10, the effect of modification is insignificant and shows no difference from the pure biodegradable polymer resin 100, and 5 wt If the % is exceeded, the brittleness of the 3D printing composite material (10) is excessive, resulting in crimping accompanying the manufacture or use of a stent printed using the 3D printing composite material (10). ) or in an expansion situation, the possibility of destruction is greatly increased.

Therefore, considering both the effect of improvement due to the inclusion of tantalum oxide 200 and the subsequent use state, the tantalum oxide 200 is added to the 3D printing composite material 10 in an amount of 1 wt% or more and 5 wt% or less based on the total weight. It is desirable to include it.

However, it is not limited to this, and as the content of the tantalum oxide 200 increases, the tensile strength and compressive strength of the biodegradable polymer resin 100 increase, so the mechanical properties are complemented and the hydrophobicity of the polymer resin surface is reduced. Based on the fact that the surface properties are complemented, the content of the tantalum oxide 200 can be adjusted to suit the environment in which the 3D printing composite material 10 will be used.

Next, the tantalum oxide 200 may have an average particle size of 50 nm or more and 80 nm or less.

Specifically, the tantalum oxide 200 fills the pores in the matrix of the biodegradable polymer resin 100 more densely as the average particle size of the tantalum oxide 200 increases. Accordingly, as the relative density increases, the mechanical properties of the biodegradable polymer resin 100 improve. This improves. Therefore, considering the pore size in the matrix of the biodegradable polymer resin 100, it is preferable that the particle size of the tantalum oxide 200 is 80 nm or less.

On the other hand, if the particle size of the tantalum oxide 200 becomes too small, there is a direct effect on cells and there is a risk of cytotoxicity, which does not correspond to the effect of improving biocompatibility aimed at by the present invention, so the tantalum oxide ( 200) It is desirable that the average particle size is 50 nm or more.

Next, the tantalum oxide 200 may be tantalum pentoxide (Ta ₂ O ₅ ).

Specifically, tantalum pentoxide (Ta ₂ O ₅ ) is a very stable material with high corrosion resistance and low reactivity. Therefore, it has the advantage that it does not corrode even when inserted into the body and does not cause unwanted side reactions or inflammation.

In addition, compared to other bioceramics, it has high biocompatibility, so it provides sufficient bonding force to prevent it from initially settling or falling out of the existing position when inserted into the body.

Next, with reference to Figure 2, a method of manufacturing a composite material 10 for 3D printing, which is another embodiment of the present invention, will be described in detail.

In the description, configurations that overlap with those of the composite material 10 for 3D printing, which is the above-described embodiment, should be interpreted in the same way, and overlapping descriptions will be omitted.

The method for producing a composite material (10) for 3D printing of the present invention includes the steps of i) producing a sol containing tantalum oxide (200) (S100); ii) mixing the biodegradable polymer resin 100 and the sol in a solvent (S200).

Hereinafter, each step will be described in detail, starting with i) the step (S100) of producing a sol containing tantalum oxide 200.

The method for manufacturing the composite material 10 for 3D printing, which is an embodiment of the present invention, adopted a method of dispersing tantalum oxide 200 in the biodegradable polymer resin 100 with high dispersion and uniformity using a sol-gel method.

Specifically, the step of preparing the sol (S100) includes a) mixing a tantalum precursor, an organic solvent, distilled water, and acid (S110); b) dispersing the mixture of step a) (S110) (S120);

At this time, the tantalum precursor in step a) (S110) may include one or more selected from the group consisting of tantalum(V) ethoxide, tantalum(V) chloride, and combinations thereof.

Additionally, the organic solvent may include one or more selected from the group consisting of isopropyl alcohol, ethanol, and combinations thereof.

Additionally, the acid may include one or more selected from the group consisting of hydrochloric acid, nitric acid, acetic acid, and combinations thereof. Next, step b) (120) may further include mixing the mixture of step a) (S110) with dichloromethane (DCM) prior to dispersion. Dichloromethane plays a role in increasing miscibility when mixed with a polymer solution containing biodegradable polymer resin (100) later.

Next, in step b) (S120), dispersion is performed using a nano-disperser to increase the degree of dispersion of the tantalum oxide (200) nanoparticles contained in the mixture prepared through step a) (S110). It can be done.

Next, ii) mixing the biodegradable polymer resin 100 and the sol in a solvent (200) will be described in detail.

The solvent in step ii) (S200) includes dichloromethane, and the biodegradable polymer resin 100 includes polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, poly-l-lactic acid, poly (lactic-co-glycolic acid), glycolide-co-trimethylene carbonate, glycolide-co-ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof. You can.

In addition, the biodegradable polymer resin 100 of step ii) (S200) may have a number average molecular weight of 40,000 or more and 50,000 or less.

In addition, the amount of the sol in step ii) (S200) is determined based on the tantalum oxide 200 contained in the sol, and in the present invention, the tantalum oxide 200 is a composite for 3D printing. Based on the total weight of the material 10, it may be included in an amount of 1 wt% or more and 5 wt% or less.

Hereinafter, another embodiment of the present invention, a 3D printed stent 20, will be described in detail with reference to FIGS. 1 and 3.

In the present invention, the 3D printed stent 20, which is an embodiment, is characterized by being manufactured by a 3D printing method using the 3D printing composite material 10, which is an embodiment described above. The shape means that it is manufactured in a general stent shape as shown in Figure 1.

Here, the 3D printing method refers to an extrusion method, preferably using hot-melt extrusion.

At this time, the 3D printed stent 20 includes the above-described composite material 10 for 3D printing, so (1) it is naturally decomposed or discharged even when inserted into the living body, so there is no problem caused by the stent remaining. (2) It has sufficient mechanical properties to withstand or support the movement of the living body, and also has the advantage of being able to adjust the mechanical properties to suit the desired environment by changing the content of tantalum oxide (200), (3) The hydrophobic surface characteristics of the polymer resin have been improved, giving it the advantage of excellent affinity with biological cells.

Next, referring to Figure 3, the 3D printed stent 20 may further include an immunosuppressant 300 on the surface.

The immunosuppressant 300 may be coated on the outer surface of the stent based on the center of the cylindrical stent, as shown in FIG. 3.

The coating method may preferably be spray coating, but is not limited thereto.

The immunosuppressant 300 is included on the outer surface of the stent and serves to suppress cell overgrowth when inserted into the body.

The immunosuppressant 300 may include one or more selected from the group consisting of sirolimus, paclitaxel, and combinations thereof.

Manufacturing example

Manufacturing method of composite material for 3D printing (10)

(1) Ta ₂ O ₅ Sol manufacturing method (S100)

i) Mix and react 0.22mg of Tantalum(V) ethoxide, 0.3ml of distilled water, 0.01ml of hydrochloric acid, and 6.25ml of isopropyl alcohol.

ii) Afterwards, add dichloromethane. Dichloromethane is intended to increase affinity with the solvent of the polymer solution to be mixed later.

iii) Next, for uniform dispersion, the solution is dispersed in a nano-disperser.

(2) 1wt%, 3wt%, 5wt% Ta ₂ O ₅ and method for manufacturing composite material for 3D printing (10) including PCL (S200)

Dissolve 2 g of PCL using 10 ml of dichloromethane as a solvent, then add the previously prepared tantalum pentoxide solution considering the desired content of tantalum oxide (200).

Specifically, 0.56ml of the sol prepared above to contain 1wt% of tantalum oxide (200) was added to the 3D printing composite material (10), 1.68ml to contain 3wt%, and 2.95ml to contain 5wt%, respectively, for 3D printing. Manufacture composite material (10) for use.

A pellet manufactured using the 3D printing composite material 10 manufactured by the above method is shown in Figure 4.

Experimental Example 1

Experiment to confirm the characteristics of composite material for 3D printing (10)

(1) Experiment to check the mixing state of composite materials for 3D printing (10)

1) Experiment overview

In this experiment, 1) DLS (Dynamic light scattering) analysis was performed on the tantalum pentoxide sol prepared according to the above production example to determine the average size of tantalum pentoxide (200) nanoparticles present in the sol. 2) TGA (Thermo-gravimetric Analysis) analysis was performed on 3D printing composite material (10) with different contents of tantalum pentoxide (200) and PCL (poly caprolactone) (100). ) was confirmed to be mixed.

2) Experiment results and analysis

(i) Figure 5 is DLS analysis data of a tantalum pentoxide solution in a method of manufacturing a composite material for 3D printing, which is an embodiment of the present invention.

Referring to Figure 5, it can be seen that the average size of tantalum pentoxide (200) nanoparticles is 50 nm to 80 nm.

The average size of the tantalum pentoxide (200) nanoparticles confirmed through the experiment is as described above. Tantalum pentoxide (200) densely fills the pores in the matrix of the biodegradable polymer resin (100) to improve mechanical properties and at the same time reduce cytotoxicity. It is a size that can achieve the desired biocompatibility without concern.

Therefore, it can be seen as a result confirming that the manufacturing method proposed by the present invention can provide a composite material 10 for 3D printing with excellent mechanical properties and biocompatibility.

(ii) Figure 6 is TGA analysis data of a composite material with different contents of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.

This TGA analysis was performed under the conditions of Equilibrate (30℃), temperature increase rate (10℃/min), and temperature range (30℃~600℃).

Referring to Figure 6, it can be seen that the mass remaining after thermal decomposition of PCL (100) increases in proportion to the increase in the content of tantalum pentoxide (200) included. Through this, it was confirmed that in the manufactured composite material for 3D printing (10), tantalum pentoxide (200) and PCL (100) were physically mixed without chemical reaction.

(2) Measurement of denaturation temperature of composite material for 3D printing (10)

In this experiment, the melting point of the composite material for 3D printing (10) according to the tantalum pentoxide content (200) was confirmed through DSC (Differential Scanning Calorimetry) analysis, and the content of tantalum pentoxide (200) proposed by the present invention was determined in 3D This was carried out to confirm whether the melting point of the printing composite material (10) could be maintained below the denaturation temperature of PCL (100).

Figure 7 is DSC analysis data of a composite material with different contents of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.

This DSC analysis was performed under the conditions of Equilibrate (35℃), heating rate (10℃/min), and temperature range (35℃~400℃).

Referring to Figure 7, the melting temperature is 62°C when it is composed of only PCL (100), 64.23°C when it contains 1wt% of tantalum pentoxide (200), 64.10°C when it contains 3wt%, and 64.36°C when it contains 5wt%. As tantalum pentoxide (200) was included, the melting point of the 3D printing composite material (10) slightly increased, but it was confirmed that it was still maintained below the denaturation temperature of PCL (100).

In other words, it was confirmed through the above results that the composite material for 3D printing (10) of the present invention can be used for 3D printing without denaturing the PCL (100).

(3) Measurement of mechanical properties of composite material for 3D printing (10)

1) Tensile strength

A dog-bone shaped specimen was manufactured using this 3D printing composite material (10) and tensile strength was measured.

Figure 8 shows tensile strength analysis data performed using composite materials with different amounts of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.

According to Figure 8(a), as the content of tantalum pentoxide (200) increases, the ultimate tensile strength tends to decrease, and according to Figure 8(b), the tensile modulus tends to increase. According to Figure 8(c), the yield strength tends to increase, and according to Figure 8(d), the elongation tends to decrease.

According to the above results, it can be seen that as the tantalum pentoxide (200) content increases, the molding manufactured using the 3D printing composite material (10) becomes stiffer and can better maintain its shape even under external stress.

2) Compressive strength

Using this 3D printing composite material (10), an 8 mm cubic specimen was manufactured and compressive strength was measured.

Figure 9 shows compressive strength analysis data performed using composite materials with different amounts of tantalum pentoxide in a composite material for 3D printing, which is an embodiment of the present invention.

According to Figure 9, it can be seen that as the tantalum pentoxide (200) content increases, the molded product manufactured using the 3D printing composite material (10) can better maintain its shape even under external stress.

(4) Biocompatibility measurement of composite materials for 3D printing (10)

A specimen using this 3D printing composite material (10) was manufactured, and vascular endothelial cells attached to the specimen for 4 hours were measured using SEM.

Figure 10 shows the results of a cell adhesion experiment performed using composite materials with different contents of tantalum pentoxide in the composite material for 3D printing, which is an embodiment of the present invention.

Referring to Figure 10, it was confirmed that as the tantalum pentoxide (200) content increased, the number of cells attached to the manufactured specimen increased, and the attached cells were better spread out.

This result is believed to be because tantalum pentoxide (200) has stability in a wide range of pH, which is advantageous in both the initial cell attachment stage and the growth stage.

Through this, it was confirmed that tantalum pentoxide (200) added to PCL (100) is effective and effective in improving the biocompatibility of the composite material (10) for 3D printing.

Experimental Example 2

Experiment to confirm the characteristics of 3D printed stent (20)

(1) SEM confirmation

Figure 11 is an image of a 3D printed stent printed using a composite material with different contents of tantalum pentoxide in the composite material for 3D printing, which is an embodiment of the present invention.

Referring to Figure 11, it can be seen that excellent output is achieved without significant difference depending on the content of tantalum pentoxide 200.

The above results indicate that when tantalum pentoxide (200) is included in the above content range, the excellent formability of poly caprolactone (PCL) (100) is maintained.

(2) Check the distribution status of tantalum pentoxide (200) nanoparticles

Figure 12 is (a) an image of a 3D printed stent manufactured using a composite material containing 5 wt% of tantalum pentoxide based on the total weight in the composite material for 3D printing, which is an embodiment of the present invention, (b), (c) are its SEM images, and (d) are its EDX analysis images.

Referring to Figures 12(a), (b), and (c), it can be seen that the stent manufactured using this 3D printing composite material 10 is printed without interruption. These results indicate that even if tantalum pentoxide (200) is included, it is sufficient to be used as a stent output material using 3D printing.

Referring to Figure 12(d), it can be seen that tantalum ions are evenly distributed in the manufactured 3D printed stent 20, and through this, a molded product manufactured using the 3D printing composite material 10 It can be seen that the expected improvement in mechanical properties and biocompatibility can be uniformly expected by including tantalum pentoxide (200) nanoparticles, and also that the sol-gel method proposed in this manufacturing method is effective. It can be seen that tantalum pentoxide (200) nanoparticles are dispersed within PCL (100).

(3) Measurement of immunosuppressant release behavior

Using spray coating on a 3D printed stent (20), which is an embodiment of the present invention, the immunosuppressant (sirolimus) (300) was loaded only on the surface and the release behavior of the immunosuppressant (sirolimus) (300) was confirmed for 30 days. It was carried out in this way.

Specifically, in the process of inserting a stent into a living body, damaged blood vessels undergo regeneration for a long time, and during this process, overgrowth of smooth muscle cells must be suppressed to prevent restenosis of blood vessels.

Therefore, this experiment was conducted for the purpose of confirming whether the 3D printed stent 20 proposed by the present invention can effectively prevent restenosis of blood vessels by slowly releasing the immunosuppressant 300.

Figure 13 is data measuring the release behavior of the immunosuppressant when the 3D printed stent, which is an embodiment of the present invention, is coated with the immunosuppressant.

According to Figure 13, it was confirmed that about 40% of the immunosuppressant (300) was released over 30 days.

Through the above results, it was confirmed that the 3D printed stent (20) of the present invention slowly and continuously releases the coated immunosuppressant (sirolimus) (300).

Therefore, it can be seen that the 3D printed stent 20 of the present invention can effectively inhibit cell overproliferation and can effectively prevent restenosis of blood vessels when inserted into a blood vessel.

The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. For example, each component described as single may be implemented in a distributed manner, and similarly, components described as distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the patent claims described below, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention.

10: Composite material for 3D printing
20: 3D printed stent
100: Biodegradable polymer resin
200: tantalum oxide
300: Immunosuppressant

Claims (14)

biodegradable polymer resin; and
Characterized by improved mechanical properties and biocompatibility, including tantalum oxide dispersed in the biodegradable polymer resin,
The biodegradable polymer resin has a number average molecular weight of 40,000 to 50,000,
The tantalum oxide is contained in an amount of 1 wt% or more and 5 wt% or less based on the total weight of the composite material for 3D printing,
The tantalum oxide is a composite material for 3D printing, characterized in that the average particle size is 50 nm or more and 80 nm or less.
According to paragraph 1,
The biodegradable polymer resin includes polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, poly-l-lactic acid, poly(lactic-co-glycolic acid), glycolide-co-trimethylene carbonate, glycolide-co A composite material for 3D printing, characterized in that it contains at least one selected from the group consisting of -ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof.
delete delete delete According to paragraph 1,
The tantalum oxide is a composite material for 3D printing, characterized in that it is tantalum pentoxide (Ta ₂ O ₅ ).
i) preparing a sol containing tantalum oxide;
ii) mixing a biodegradable polymer resin and the sol in a solvent; a method for manufacturing a composite material for 3D printing, comprising:
The biodegradable polymer resin in step ii) has a number average molecular weight of 40,000 to 50,000,
The tantalum oxide is contained in an amount of 1 wt% or more and 5 wt% or less based on the total weight of the 3D printing composite material,
A method of manufacturing a composite material for 3D printing, characterized in that the tantalum oxide has an average particle size of 50 nm or more and 80 nm or less.
In clause 7,
The step of preparing the sol is,
a) mixing tantalum precursor, organic solvent, distilled water and acid;
b) dispersing the mixture of step a) above; A method of manufacturing a composite material for 3D printing, comprising:
According to clause 8,
The tantalum precursor includes at least one selected from the group consisting of tantalum(V) ethoxide, tantalum(V) chloride, and combinations thereof,
The organic solvent includes at least one selected from the group consisting of isopropyl alcohol, ethanol, and combinations thereof,
A method of manufacturing a composite material for 3D printing, wherein the acid includes at least one selected from the group consisting of hydrochloric acid, nitric acid, acetic acid, and combinations thereof.
In clause 7,
The solvent in step ii) includes dichloromethane,
The biodegradable polymer resin includes polycaprolactone, polyglycolic acid, polylactic acid, polyorthoester, phosphazene, polypeptide, polydioxanone, poly-l-lactic acid, poly(lactic-co-glycolic acid), glycolide-co-trimethylene carbonate, glycolide-co A method of manufacturing a composite material for 3D printing, characterized in that it includes at least one selected from the group consisting of -ε-caprolactone, polyglyconate, polyglactin, poly ethylene glycol, poly ethylene oxide, and combinations thereof.
delete A 3D printed stent, characterized in that it is manufactured by 3D printing using the composite material for 3D printing of claim 1.
According to clause 12,
A 3D printed stent, characterized in that it further comprises an immunosuppressant coated on the surface of the 3D printed stent.
According to clause 13,
A 3D printed stent, characterized in that the immunosuppressant includes at least one selected from the group consisting of sirolimus, paclitaxel, and combinations thereof.

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