KR102166991B1 - Method for controling pores in preparation of porous scaffold by FDM 3D printing - Google Patents

Abstract

In the present invention, in manufacturing a porous scaffold using a fused deposition modeling (FDM) 3D printer, a thermosetting biodegradable polymer having a specific range of heat capacity in a molten state is selected to maintain the shape of the pores. It relates to a method for manufacturing a porous scaffold, including the steps, and a porous scaffold for medical use, in which the size and shape of the pores are controlled.

Description

Method for controlling pores in preparation of porous scaffold by FDM 3D printing {Method for controlling pores in preparation of porous scaffold by FDM 3D printing}

In the present invention, in manufacturing a porous scaffold using a fused deposition modeling (FDM) 3D printer, a thermosetting biodegradable polymer having a specific range of heat capacity in a molten state is selected to maintain the shape of the pores. It relates to a method for manufacturing a porous scaffold, including the steps, and a porous scaffold for medical use, in which the size and shape of the pores are controlled.

This intellectual property right is a study conducted with the support of the Korea Institute of Industrial Technology's own research project "World's No. 1 Production Technology Project in 2017 (2/4) (Kitech UR-17-0018)".

Recently, studies on bone regeneration and organ regeneration through a histologic approach have been actively conducted, and for this purpose, studies on the development of a scaffold for bone defect filling, that is, a medical scaffold for transplantation, are also actively conducted.

Existing methods for manufacturing medical scaffolds have been using various methods such as electrospinning, solvent casting, and particle etching, but there are disadvantages such as the risk of residual solvents, a limited form of scaffold, and complicated procedures for manufacturing.

Accordingly, there is a need for a method of manufacturing a medical scaffold capable of satisfying the demands of many patients who desire an organ transplant by simplifying the complex manufacturing process, which is a problem of the existing medical biological scaffold.

A 3D (3-Dimension) printer is an equipment that uses filaments to melt it with an extruder and builds up a three-dimensional shape by stacking layers to a fine thickness through a nozzle. 3D printing is spreading its use in various fields. In addition to the automotive field composed of a large number of parts, it is used by many manufacturers for a variety of purposes, from medical human models, household products such as toothbrushes and razors, and clothing.

In recent years, through 3D printer modeling, it is possible to rapidly manufacture damaged bone/cartilage as a substitute material with a shape and characteristics suitable for the affected part of a patient, and a customized organ manufacturing is possible through individual somatic cell division. There is a need for development of a method for manufacturing a medical scaffold.

Accordingly, the inventors of the present invention have worked hard to find a method for forming pores having a predetermined size and maintained in a distinct shape in manufacturing a polymer-based porous scaffold by a single process using a 3D printer. By using a filament additionally containing a foaming agent, but by selecting a polymer in consideration of heat capacity, it was confirmed that the pore size and shape of the resulting porous scaffold were determined, and the present invention was completed.

One object of the present invention is to produce a porous scaffold using a fused deposition modeling (FDM) 3D printer, in order to maintain the shape of the pores, in order to maintain a heat capacity of 5 to 100 J/K in a molten state. A first step of selecting a thermosetting biodegradable polymer having; A second step of preparing a filament for 3D printing by blending the selected polymer and a foaming agent; And a third step of supplying the filament obtained from the second step to a fused deposition modeling (FDM) 3D printer, and outputting the print while maintaining the temperature of the printer nozzle above the decomposition temperature of the foaming agent. Is to do.

Another object of the present invention is to provide a medical porous scaffold manufactured by the above method, in which the size and shape of pores are controlled.

As an aspect for achieving the above object, the present invention is in the molten state in order to maintain the shape of the pores in manufacturing a porous scaffold using a fused deposition modeling (FDM) 3D printer. A first step of selecting a thermosetting biodegradable polymer having a heat capacity of 100 J/K; A second step of preparing a filament for 3D printing by blending the selected polymer and a foaming agent; And a third step of supplying the filament obtained from the second step to a fused deposition modeling (FDM) 3D printer, and outputting the print while maintaining the temperature of the printer nozzle above the decomposition temperature of the foaming agent. do.

Specifically, an object of the present invention is to discover a method capable of controlling the shape of pores formed to have a predetermined size while manufacturing a porous scaffold based on a polymer, which can be achieved with a simple process.

In manufacturing the porous scaffold, the present invention is based on using a fused deposition modeling (FDM) method among 3D printing methods. The FDM is a method of laminating and molding by melting the material by heat and extruding it through a nozzle at a certain pressure. The form of the supplied material is in the shape of a filament, and is placed on a roll such as a protective cartridge or thread. It is wound and supplied continuously. These solid materials are softened and extruded into a material close to the liquid phase while passing through a temperature-controlled melt-extruded head, and a three-dimensional model is created through a further fusion lamination process. The characteristics of the FDM method are that the surface is rough and the precision is low compared to other types of printers, but the raw material is cheap, the strength is strong, and the post-processing process is easy.

The porous scaffold needs to adjust the size and shape of the pores according to its purpose. Furthermore, this control of pores is also related to the strength of the scaffold. For example, if the porosity is too large or the porosity is high, it is difficult to maintain the shape of the scaffold or it may be easily broken even with small stimulation. Examples of pore types include closed pores and open pores. In the case of open pores, the pores are connected to the surface and a kind of channel connected to each other is formed inside, so that the material can enter and exit.

As an example of such a porous scaffold, a medical scaffold is implanted in vivo for the purpose of tissue regeneration, and a scaffold made of a biodegradable polymer may be mainly used for bone tissue and cartilage tissue. At this time, in order to promote tissue regeneration, cells such as stem cells penetrate and adhere to the inside of the scaffold for proliferation and/or differentiation, and growth factors, including nutrients for proliferation and/or differentiation, as well as cell entry and exit. It is important that the supply of materials such as etc. is easily accessible. Therefore, it is preferable that the scaffold used for this has a size and shape suitable for the site to be implanted, as well as pores of an appropriate size that pass from its surface to the inside. In the present invention, the scaffold is manufactured by printing in a 3D modeled form, but it is based on a thermosetting biodegradable polymer and uses a filament containing a foaming agent in a predetermined content to have an input shape when output through a high-temperature nozzle. It is characterized by having pores that are connected from the surface to the inside through decomposition of the blowing agent.

Specifically, in the method of manufacturing a scaffold according to the present invention, the pores may have an average diameter of 10 to 100 μm. These pores may be formed by gas evolution due to decomposition of the blowing agent due to the temperature of the nozzle during output. The FDM type 3D printer used in the present invention is easy to drive, but the resolution is not high. Therefore, it may be difficult to implement pores of a small size of several tens of μm through 3D modeling. Furthermore, the scaffold of the present invention may be designed to have additional pores of a larger scale through printer modeling during the output of the third step.

On the other hand, the second step may be carried out below the decomposition temperature of the blowing agent. In this case, as the foaming agent, a material that decomposes at a temperature equal to or higher than the melting point of the polymer may be selected.

For example, in order to be used as a biomaterial, the scaffold must satisfy various essential properties, and its representative features include 1) biodegradability and non-toxicity, 2) structural stability, 3) low immune reactivity, 4) inhibition of thrombus formation, 5 ) Hydrophilicity, 6) biocompatibility, etc. In the present invention, a chemical hydrolyzable biodegradable polymer was used to prepare a medical scaffold that satisfies this.

For example, as the thermosetting biodegradable polymer, polybutylene succinate (PBS), polylactic acid (PLA), poly(butylene adipate-co-terephthalate) (poly(butylene adipate-co- terephthalate); PBAT), polyethylene (PE), polydioxanone, poly(β-hydroxybutyrate)), poly(hydroxyvalerate) (poly(hydroxyvalerate) ), poly(ε-caprolactone) (poly(ε-caprolactone)), polyglycolic acid, poly(DETOSU-1,6HD-t-CDM orthoester), poly(DTE carbonate), poly(methyl 2-cya Noacylate), poly[(p-methylphenoxy)(ethyl glycinato)phosphazene] or poly(bis(p-carboxyphenoxy)propane-sebacic acid) alone or in combination of two or more However, it is not limited thereto.

In the present invention, the "melting point of a polymer" may be a melting point of a pure polymer, but is not limited thereto. For example, in the case of a polymer, when two or more kinds of polymers are mixed, or when an additive is included, such as the foaming agent in the present invention, the melting point thereof may be changed. Therefore, the melting point of the polymer may include both the melting point of the pure polymer as well as the melting point changed by the material added thereto.

For example, in the case of forming open pores, it is preferable to select the thermosetting biodegradable polymer having a heat capacity of 5 to 100 J/K in a molten state. In the case of using a polymer with a heat capacity of less than 5 J/K in the molten state, the viscosity in the molten state decreases, thereby lowering the process speed, and the formation of pores in the polymer melt due to gas evolution due to decomposition of the blowing agent may be inhibited. In the case of more than 100 J/K, heat transfer to the foaming agent is relatively delayed due to the large amount of heat absorption by the polymer. Accordingly, the shape of the pores collapses by inhibiting or delaying the decomposition of the foaming agent forming micropores from the inside of the scaffold. It can be difficult to form pores in the form of open channels that reach the surface. The pores in the form of open channels are only meant to be connected to the surface so that the material can enter and exit, but it does not mean that these pores must be connected to each other. As long as these pores do not destroy the structure of the scaffold itself, They may be connected or cross each other inside the scaffold, but the present invention is not limited thereto.

Further, the thermosetting biodegradable polymer may be selected from materials having a melt flow index (MI) of 2.5 to 30 g/10 min at 210°C. For example, when the melt index of the polymer is as low as 2.5 g/10 min, the foaming efficiency of the foaming agent may decrease due to high viscosity. On the other hand, when the melt index of the polymer is more than 30 g/10 min, the viscosity of the polymer is too low, and it may be difficult to maintain the pores formed by the foaming agent.

For example, the foaming agent may be a material having a gas volume of 100 to 350 mL/g, which is decomposed at a temperature above its decomposition temperature, for example, a printer nozzle temperature to release gas. When using a foaming agent having a gas volume of less than 100 mL/g, it may be difficult to form a microstructure of a desired size and/or porosity. When using a foaming agent having a gas volume of more than 350 mL/g, the pores The size of the pore becomes larger than necessary or the porosity increases, and thus the formed pore structure may be easily collapsed.

Examples of the foaming agent include azodicarbonamide, modified azodicarbonamide, p-toluenesulfonyl semicarbazide, p-toluenesulfonyl hydrazide, p-toluenesulfonyl hydrazide), p-toluenesulfonyl acetone hydrazide, 5-phenyltetrazole, sodium bicarbonate, or a combination thereof, but is not limited thereto. . For example, the foaming agent may be a material that is decomposed in the range of 130 to 250° C. to generate gas, but is not limited thereto. Specifically, the foaming agent having a decomposition temperature at a low temperature of less than 130° C. is easily decomposed and foamed while passing through a high-temperature nozzle, so that it may be difficult to control pore formation. On the other hand, the foaming agent having a decomposition temperature at a high temperature of more than 250° C. may cause difficulty in foaming at a set nozzle temperature, or the trouble of having to significantly increase the temperature of the nozzle for foaming. The modified azodicarbonamide may be a material modified to further include a vinyl group so as to control an early foaming phenomenon during the foaming process, and may be a material having a decomposition temperature controlled by such modification. For example, azodicarbonamide decomposes at 180 to 205°C, but azodicarbonamide modified to have a vinyl group decomposes at a lower temperature of 140 to 160°C.

For example, in the method of manufacturing a porous scaffold according to the present invention, the filament used therein may include 0.1 to 10 wt% of the foaming agent based on the total weight of the filament. If the content of the foaming agent in the filament is less than 0.1 wt%, it may be difficult to form fine pores of a desired size and/or porosity, such as 100 μm, and when the content of the foaming agent exceeds 10 wt%, it may be difficult to form excessive pores. It can be difficult to maintain the structure of the scaffold.

In the third step, the temperature of the printer nozzle may be specifically selected from 180 to 230°C, but is not limited thereto. The higher the temperature of the nozzle, the easier it is to decompose the foaming agent, and accordingly, the cumulative gas emission amount can be increased, but if the temperature is higher than a certain level, the foaming efficiency may be lowered. Therefore, as described above, the melting point of the polymer as well as the decomposition temperature of the foaming agent can be considered at the same time and appropriately selected.

The filament preferably has an average diameter of 1.7 to 1.8 mm, but is not limited thereto. However, the standard of the filament exemplified is proposed in consideration of the method of using the FDM printer, and it is preferable to have a diameter of about 1.75 mm to meet the standard of the currently commercialized FDM 3D printer. However, it is obvious to those skilled in the art that when the standard of the device is changed, the standard of the filament can also be appropriately changed within the allowable error range thereof.

As another aspect, the present invention provides a medical porous scaffold manufactured by the above method.

As described above, the scaffold prepared by the method of the present invention can be usefully used as an implant for tissue regeneration, as it has pores of various sizes that pass from the surface to the inside so as to facilitate the entry of cells and/or materials. .

According to the present invention, a method for manufacturing a medical scaffold using a 3D printer filament prepared by mixing at a predetermined temperature to contain a polymer selected in consideration of heat capacity and a foaming agent mixed in a predetermined amount A porous scaffold having pores of a controlled size can be provided through a simple single step of outputting while maintaining the temperature at a certain level.

1 is a diagram schematically showing a method of manufacturing a medical porous scaffold by 3D printing using a foamable filament according to the present invention.
2 is a view showing the DSC analysis results according to the content of the foaming agent of the filament containing polylactic acid as a biodegradable polymer according to the present invention and azodicarbonamide as a foaming agent.
Figure 3 is a cross-section and surface FE- according to the content of the foaming agent of the scaffold prepared in the form of a monofilament by printing a filament containing polylactic acid as a biodegradable polymer according to the present invention and azodicarbonamide as a foaming agent by a 3D printer. It is a diagram showing the results of SEM analysis. (a) and (b) are the cross-section and surface of the scaffold made of a filament having a foaming agent content of 1 wt%, and (c) and (d) and (e) and (f) are the foaming agent contents of 3 wt% and 5 wt%, respectively. The cross section and surface of a scaffold made of filaments are shown.
4 is a view showing the result of analyzing the pore formation characteristics according to the 3D printer nozzle temperature by FE-SEM. A filament containing polylactic acid as a biodegradable polymer and 1 wt% of azodicarbonamide as a blowing agent was used, and the temperature of the nozzle on the left was adjusted to 165°C lower than the decomposition temperature of the blowing agent, and on the right to 205°C. A cross section of a scaffold is shown.
FIG. 5 is a diagram showing the results of analyzing cross-sectional pore characteristics of a scaffold output in a bulk form using a filament containing polylactic acid as a biodegradable polymer and azodicarbonamide in a content of 1 wt% as a blowing agent by FE-SEM .
6 is a diagram showing an example of a structure in which a macropore pattern is formed by controlling a filling density through 3D printing modeling.
7 is a diagram showing the results of analyzing the surface of a porous scaffold (denoted as D100, D80 and D60, respectively) prepared by adjusting the filling density to 100%, 80% and 60% through 3D printing modeling with FE-SEM to be. As a control, a structure printed with a filling density of 100% using a commercial PLA filament (denoted as Neat PLA) was used.
FIG. 8 is a diagram showing the results of analyzing a cross section of a porous scaffold outputted in a bulk form with a filling density of 100% through 3D printing modeling using FE-SEM.
FIG. 9 is a diagram showing the results of analyzing the pore characteristics according to the packing density of a porous scaffold prepared by 3D printing by a porosity measurement method (Hg-porosimetry) using mercury penetration.
10 is a view showing the DSC analysis results according to the type of biodegradable polymer resin used in the foamable filament according to the present invention. The polymer resin includes polyethylene (PE), polybutylene succinate (PBS), polylactic acid (PLA), and poly(butylene adipate-co-tere) instead of polybutylene succinate. Phthalate) (poly(butylene adipate-co-terephthalate); PBAT) was used.
FIG. 11 is a diagram showing the results of analyzing a cross section of a bulk scaffold prepared by 3D printing a filament containing PE, PBS, PLA, and PBAT as a biodegradable polymer and azodicarbonamide as a foaming agent, respectively, by SEM.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for describing the present invention in more detail, and the scope of the present invention is not limited by these examples.

Example 1: Preparation of FDM 3D printer foamable filament 1

After mixing 99 g of polylactic acid (PLA) pellets and 1 g of azodicarbonamide (ADA) powder as a blowing agent, and uniformly blending at 180° C. at 50 rpm using a single extruder A filament for an FDM 3D printer was prepared (diameter: 1.75 mm).

Example 2: Preparation of FDM 3D printer foamable filament 2

A filament was prepared in the same manner as in Example 1, except that the amounts of polylactic acid and azodicarbonamide were changed to 97 g and 3 g, respectively.

Example 3: Preparation of FDM 3D printer foamable filament 3

A filament was prepared in the same manner as in Example 1, except that the amounts of polylactic acid and azodicarbonamide were changed to 95 g and 5 g, respectively.

Example 4: Preparation of foamable filament for FDM 3D printer 4

A filament was prepared in the same manner as in Example 3, except that modified azodicarbonamide (Geumyang) was used instead of azodicarbonamide as a foaming agent.

Example 5: Preparation of foamable filament for FDM 3D printer 5

A filament was prepared in the same manner as in Example 3, except that p-toluenesulfonyl semicarbazide (PTSS) was used instead of azodicarbonamide as a blowing agent.

Experimental example 1: Analysis of filament properties

A tensile test was performed on the filaments prepared according to Examples 1 to 5 according to ASTM D882. As a result, it exhibited a tensile strength of 104.5 to 115.5 KPa in the MD direction, 137.9 to 152.1 KPa in the TD direction, and an elongation at break of 160%.

Example 6 to 10: 3D Porosity using printer Scaffold Produce

The filaments prepared according to Examples 1 to 5 were supplied to an Edison Multi 3D printer (ROKIT) and printed to prepare a scaffold. At this time, the temperature of the 3D printer nozzle was maintained at 205°C or higher. The output result was recovered by cooling so that there was no influence of morphology.

Experimental example 2: According to the type of blowing agent Scaffold Property analysis

In order to check the effect according to the type of foaming agent, first, the physical properties of the foaming agents used in the scaffolds prepared according to Examples 6 to 10 were analyzed, and the results are shown in Table 1 below.

blowing agent Exterior Decomposition temperature(℃) Gas volume (mL/g) Azodicarbonamide
(Example 8) Fine Yellow Powder 200 to 205 263 to 322 Modified azodicarbonamide
(Example 9) Fine Yellow Powder 140 to 160 175 to 195 p-toluenesulfonyl semicarbazide
(Example 10) Fine Yellow Powder 228 to 232 115 to 155

Experimental example 3: according to the content of the filament foaming agent Scaffold DSC analysis

The scaffolds prepared according to Examples 6 to 10 were analyzed by differential scanning calorimetry (DSC), and the results are shown in FIG. 2. As shown in Figure 2, as the content of the foaming agent for the polymer resin in the filament increases (from Examples 1 to 3), the matrix polymer such as the glass transition temperature (T _g ) and the melting point (T _m ) due to the additive It was confirmed that the thermal properties decreased, and furthermore, it was confirmed that the dispersion degree gradually increased as the content of the blowing agent increased.

Experimental example 4: Porosity printed in the form of a mono filament Scaffold Section and surface analysis

The cross section and surface of the porous scaffold printed in the form of filaments according to Examples 6 to 8 were observed with FE-SEM, and the results are shown in FIG. 3. As a result of analyzing the image of FIG. 3, it was confirmed that pores having a diameter of 45 to 220 μm were randomly formed in the printed scaffold. Meanwhile, the printed monofilament-shaped scaffold was confirmed to have a diameter of about 450 μm. In addition, according to Examples 6 to 8, from the surface image of the scaffold prepared using filaments containing a foaming agent at 1 wt%, 3 wt%, and 5 wt%, respectively, for the polymer, to the surface as the content of the foaming agent in the filament increased. It was confirmed that the prolonged pores increased. Finally, it is an important element to have an appropriate level of pores that extend to the surface and are connected to each other so as to facilitate entry and exit of substances and/or cells, as an object of providing a medical scaffold for use as an in vivo implant.

Comparative example 1: by low temperature printing Scaffold Produce

A scaffold was manufactured in the same manner as in Example 6, but the temperature of the nozzle was lowered to 165° C. lower than the decomposition temperature of the foaming agent and printed.

Experimental example 5: 3D Analysis of pore formation characteristics according to printer nozzle temperature

According to Example 6 and Comparative Example 1, the pore-forming characteristics of the porous scaffold prepared by varying only the nozzle temperature of the printer were analyzed by FE-SEM, and the results are shown in FIG. 4. As shown on the left side of FIG. 4, when output at 165° C. lower than the decomposition temperature of azodicarbonamide, the foaming agent contained in the filament, pores were not yet formed, but as shown on the right side of FIG. 4, optimal decomposition When outputting at a temperature of 205°C, it was confirmed that pores were formed in the cross section and the surface.

Experimental example 6: Bulk Scaffold Analysis of section pore characteristics

A scaffold was prepared in the same manner as in Example 6, but was repeatedly performed to produce a bulk type instead of a monofilament type, and the cross-section thereof was analyzed by FE-SEM, and the results are shown in FIG. 5. As shown in FIG. 5, pores having a size of 60 to 210 μm were randomly formed inside, and the diameter of each layer was about 400 μm.

Example 11 to 13: Filling density Controlled double pore Scaffold Produce

200 g of polylactic acid pellets and 10 g of azodicarbonamide powder were mixed (5 phr), and then uniformly blended at 180° C. at 300 rpm using a single compressor to prepare a filament for an FDM 3D printer (diameter: 1.75 mm). ).

The prepared filament was supplied to an Edison Multi 3D printer, and a scaffold was manufactured by printing while maintaining the nozzle temperature at 205°C. At this time, through 3D printing modeling, the fill density is adjusted to 100% (PLA03 D100), 80% (PLA03 D80), and 60% (PLA03 D60), respectively, with a macroporous scaffold (10 mm × 10 mm). ×3 mm) was prepared. The output result was recovered by cooling so that there was no influence of morphology.

Experimental example 7: Filling Double pores according to density Scaffold Analysis of pore characteristics

An example of a scaffold manufactured by controlling the filling density through 3D printing modeling is shown in FIG. 6. In addition, the surface morphology of the scaffold having a filling density of 100%, 80% and 60%, prepared with a filament containing a foaming agent according to Examples 11 to 13 was observed with FE-SEM, and the results are shown in FIG. Done. For comparison, a scaffold having a filling density of 100% was prepared by the same method using a commercial PLA filament containing only pure PLA, that is, without a foaming agent (Neat PLA), and compared and observed by the same method. As shown in FIG. 7, when a commercial PLA filament was used, not only did not have macropores, but also micropores exposed to the surface were not observed at all because it was manufactured at 100% filling density. On the other hand, the scaffolds of Examples 13 to 15 made of filaments containing the foam of the present invention not only have macropores of patterns and sizes implemented according to the filling density controlled by 3D printing modeling, but also have a foaming agent during the printing process. It showed a double pore structure with micro-level pores connected to the surface and the interior of the scaffold formed by the decomposition of For example, in the case of a sample with a packing density of 60% (PLAO3 D60), macro pores of 200 to 300 μm size implemented through 3D printing modeling were introduced, and as confirmed through surface observation, 40 to 70 μm size It was confirmed to have additional micropores. These micropores were formed in a similar pattern in samples of 100% and 80% filling density regardless of the filling density.

Meanwhile, as a representative example, according to Example 11, a filament containing a foaming agent was supplied and output at a filling density of 100%, that is, a bulk-type scaffold was cut using liquid nitrogen, and its cross section was analyzed by SEM. The results are shown in FIG. 8. When the filling density was set to 100%, macropores did not appear, and micropores due to gas generated by decomposition of the blowing agent generated during output were evenly present inside the scaffold.

Further, by measuring the porosity using mercury infiltration (Hg-porosimetry), the porosity and total penetration volume of these scaffolds according to the packing density, that is, the volume of pores, were measured and shown in FIG. 9 and Table 2 below. As shown in Table 2, the scaffolds of Examples 11 to 13 showed remarkably high porosity and total penetration volume compared to the scaffold output with a filling density of 100% using a commercial PLA filament, and these values are the filling density. Increased as is decreased. At this time, the bulk scaffold made of a commercial PLA filament also exhibited some porosity due to the porosity of PLA itself. In addition, as shown in FIG. 9, the scaffold made of the filament containing the blowing agent according to the present invention exhibited a peak around 30 μm and an additional peak at about 90 μm added by the blowing agent.

Sample name Porosity (%) Total intrusion volume (mL/g) Neat PLA 13.2 0.1158 PLAO3 D100 18.2 0.1715 PLAO3 D80 28.8 0.3044 PLAO3 D60 37.2 0.4639

Example 14: Using a foamable filament based on PBS as a biodegradable polymer Scaffold Produce

A biodegradable porous scaffold was prepared in the same manner as in Example 11, except that polybutylene succinate (PBS, EnPol G4560J, Lotte Fine Chemicals) was used instead of polylactic acid as a biodegradable polymer.

Example 15: As a biodegradable polymer PBAT Based on foamable filaments Scaffold Produce

As a biodegradable polymer, except for using poly(butylene adipate-co-terephthalate) (poly(butylene adipate-co-terephthalate); PBAT, EnPol PBG 7070, Lotte Fine Chemical) instead of polylactic acid. A biodegradable porous scaffold was prepared in the same manner as in Example 11.

Comparative example 1: As a biodegradable polymer PE Based on foamable filaments Scaffold Produce

A biodegradable porous scaffold was prepared in the same manner as in Example 11, except that polyethylene (PE, UF-414, Lotte Chemical) was used instead of polybutylene succinate as a biodegradable polymer.

Experimental example 8: Analysis of properties of basic polymer resin

In order to manufacture a biodegradable polymer scaffold having a desired porosity using a 3D printer, the physical properties according to the type of the basic polymer resin were first analyzed, and were compared and summarized in Table 3 below. In addition, these polymer resins were analyzed by differential scanning calorimetry (DSC), and the results are shown in FIG. 10. As shown in Table 3 below, these polymer resins exhibited different heat capacities, glass transition temperatures, melting points, density and/or melt flow index (MI). Accordingly, in order to check the effect of the physical properties of the polymer resin on the manufacture of the porous scaffold, according to Examples 11, 14, 15 and Comparative Example 1, respectively, based on PLA, PBS, PBAT, and PE, a foaming agent was further included. A porous scaffold was manufactured by manufacturing a filament for 3D printer and printing it with a 3D printer while supplying it.

Example 11 Example 14 Example 15 Comparative Example 1 Base resin PLA PBS PBAT PE Heat capacity (J/K) 36.8 64.6 6.75 104.3 T _g (℃) 60 to 65 -42 to -18 40 to 52 -34 to -10 T _m (℃) 150 to 160 115 130 130 to 170 Density (g/mL) 1.31 to 1.39 1.22 to 1.28 1.24 to 1.31 0.82 to 0.90 MI(g/10min) 7 to 9 13 to 20 3 to 5 2

Experimental example 9: 3D Porosity produced by the printer Scaffold Analysis of pore characteristics

According to Examples 11, 14, 15 and Comparative Example 1, a cross section of a porous scaffold prepared from filaments containing azodicarbonamide in the same amount as a foaming agent, but having PLA, PBS, PBAT and PE as basic polymers, respectively. Observation by SEM, and the results are shown in FIG. 11. According to Table 3, the heat capacity of the polymer resin decreased in the order of PE>PBS>PLA>PBAT, and compared with FIG. 11, based on PBS, PLA and PBAT having a low heat capacity value of 100 J/K or less. In the case of the scaffold, fine pores having a size of 20 to 60 μm were randomly distributed inside the scaffold, and these pores extended to the surface, but in the case of a scaffold based on PE with a heat capacity value exceeding 100 J/K Despite the fact that the filaments were made of the same type and content of the foaming agent, only traces of crushed pores were observed, but no distinct spherical pores were observed. This was considered to be because the pores formed by the decomposition of the foaming agent at the time of printing were collapsed by heat due to the high heat capacity of the polymer.

Furthermore, the effect of the melt index on pore formation was confirmed. As shown in Table 3, the polymer resin used in the present invention showed a melting index decreasing in the order of PBS>PLA>PBAT>PE. Compared with FIG. 11, it was confirmed that the higher the melt index, that is, the lower the viscosity, the higher the foaming efficiency.

Claims (13)

In manufacturing a porous scaffold using a fused deposition modeling (FDM) 3D printer,
A first step of selecting a thermosetting biodegradable polymer having a heat capacity of 5 to 100 J/K in a molten state to maintain the shape of the pores;
A second step of preparing a filament for 3D printing by blending the selected polymer and a foaming agent; And
Including a third step of supplying the filament obtained from the second step to a fused deposition modeling (FDM) 3D printer, and outputting the printer while maintaining the temperature of the printer nozzle above the decomposition temperature of the foaming agent,
During the third step, the thermosetting biodegradable polymer has a heat capacity of 5 to 100 J/K, thereby forming micropores in the form of open channels connected to the surface of the porous scaffold,
A method of forming macropores having a larger pore size than the micropores by controlling the fill density to less than 100% during the third step.
The method of claim 1,
The method wherein the pores have an average diameter of 10 to 100 μm.
The method of claim 1,
The method wherein the pores are formed by decomposition of the blowing agent.
The method of claim 1,
The method wherein the foaming agent is decomposed at a temperature above the melting point of the polymer selected from the first step.
The method of claim 1,
The second step is a method that is carried out below the decomposition temperature of the blowing agent.
The method of claim 1,
The thermosetting biodegradable polymer is polybutylene succinate (PBS), polylactic acid (PLA), poly(butylene adipate-co-terephthalate) (poly(butylene adipate-co-terephthalate)); PBAT), polyethylene (PE), polydioxanone, poly(β-hydroxybutyrate)), poly(hydroxyvalerate)), poly (ε-caprolactone)(poly(ε-caprolactone)), polyglycolic acid, poly(DETOSU-1,6HD-t-CDM orthoester), poly(DTE carbonate), poly(methyl 2-cyanoacylate) ), poly[(p-methylphenoxy)(ethyl glycinato)phosphazene], and poly(bis(p-carboxyphenoxy)propane-sebacic acid) any one or more selected from the group consisting of .
The method of claim 1,
The thermosetting biodegradable polymer has a melt flow index (MI) of 1 to 30 g/10 min at 210°C.
The method of claim 1,
The foaming agent is a material having a gas volume of 100 to 350 mL/g, which is decomposed at a temperature above its decomposition temperature to release a gas.
The method of claim 1,
The blowing agent is azodicarbonamide, modified azodicarbonamide, p-toluenesulfonyl semicarbazide, p-toluenesulfonyl hydrazide ), p-toluenesulfonyl acetone hydrazide (p-toluenesulfonyl acetone hydrazide), 5-phenyltetrazole (5-phenyltetrazole) and sodium bicarbonate (sodium bicarbonate) in any one or more selected from the group consisting of.
The method of claim 1,
The method of the foaming agent is contained in an amount of 0.1 to 10% by weight based on the total weight of the filament.
The method of claim 1,
Wherein the filament has an average diameter of 1.7 to 1.8 mm.
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