KR20180054503A - Method for preparation of dual-pore scaffold for medical use by using FDM 3D printing - Google Patents

Abstract

The present invention relates to a method for manufacturing a dual pore scaffold and a medical dual pore scaffold manufactured thereby. The method comprises a step of supplying a 3D printing filament prepared by blending a thermosetting biodegradable polymer and a foaming agent decomposed at a temperature equal to or higher than a melting point of the polymer at a decomposition temperature of the foaming agent or less to a fused deposition modeling (FDM) 3D printer, and then printing while maintaining a temperature of a printer nozzle at or above the decomposition temperature of the foaming agent. A first pore has an average diameter of 10-100 μm and a second pore has an average diameter of 100-1000 μm.

Description

TECHNICAL FIELD The present invention relates to a dual-pore scaffold for medical use using FDM 3D printing,

The present invention provides a 3D printing filament prepared by blending a thermosetting biodegradable polymer and a foaming agent decomposed at a temperature higher than the melting point of the polymer at a decomposition temperature of the foaming agent or lower, to a Fused Deposition Modeling (FDM) 3D printer Of the double pore scaffold having an average pore size of 10 to 100 mu m and a second pore size of 100 to 1000 mu m in average diameter, including the step of outputting while maintaining the temperature of the printer nozzle at or above the decomposition temperature of the foaming agent And a medical dual-pore scaffold prepared thereby.

Recently, studies on bone regeneration and organ regeneration through the tissue engineering approach have been actively carried out. For this purpose, researches on the development of scaffolds for bone defect filling, that is, medical scaffolds for implantation, have been actively conducted.

Conventionally, various methods such as electrospinning, solvent casting, and particle etching have been used for manufacturing a medical scaffold, but there have been disadvantages such as a risk of residual solvent, a scaffold in a limited form, and complicated procedures for manufacturing.

Accordingly, there is a need for a method of manufacturing a medical scaffold that can meet the needs of a large number of patients who wish to organ transplant by simplifying a complicated manufacturing process, which is a problem of a conventional medical bio scaffold.

A 3D (3-Dimension, 3-dimensional) printer is a device that melts with an extruder using a filament, and builds a three-dimensional shape by stacking layers with fine thickness through nozzles. 3D printing is spreading in various fields. In addition to the automotive field consisting of many parts, it is used by many manufacturers for a variety of applications ranging from household products such as medical manikins, toothbrushes, razors, and clothing.

In recent years, 3D printer modeling has been used to rapidly produce damaged tissues such as bone / cartilage as a substitute material suitable for a patient's individual lesion, and to customize a long-term manufacturing process by disrupting individual somatic cells There is a need to develop a method of manufacturing a medical type scaffold.

Accordingly, the present inventors have found that, in the manufacture of medical scaffolds having various sizes of pores in the form of open channels connected to the inside from the surface so as to facilitate growth / proliferation of cells and / As a result, it has been found that a patient-customized scaffold is manufactured through 3D printer modeling using an FDM 3D printer, and a polymer and a foaming agent having a predetermined heat capacity and / or melt index are selected and combined, Accordingly, it has been confirmed that a dual pore scaffold having pores having a size of several tens of micrometers and several hundreds of micrometers can be manufactured in a single process by using the filament manufactured by mixing at a predetermined temperature, and the present invention has been completed.

One object of the present invention is to provide a method for preparing a 3D printing filament by blending a thermosetting biodegradable polymer and a foaming agent decomposed at a temperature equal to or higher than the melting point of the polymer at a decomposition temperature or lower of the foaming agent, And a second step of supplying the filament obtained from the first step to a Fused Deposition Modeling (FDM) 3D printer to output the temperature of the printer nozzle while maintaining the temperature of the printer nozzle at or above the decomposition temperature of the blowing agent, To provide a process for producing a dual pore scaffold having a first pore of 10 to 100 μm and a second pore of an average diameter of 100 to 1000 μm.

Another object of the present invention is to provide a medical dual-pore scaffold prepared by the above method.

In order to accomplish the above object, the present invention provides a method for preparing a 3D printing filament by blending a thermosetting biodegradable polymer and a foaming agent decomposed at a temperature equal to or higher than the melting point of the polymer at a decomposition temperature or lower of the foaming agent, ; And a second step of supplying the filament obtained from the first step to a Fused Deposition Modeling (FDM) 3D printer to output the temperature of the printer nozzle while maintaining the temperature of the printer nozzle at or above the decomposition temperature of the blowing agent, A first pore of 10 to 100 mu m and a second pore of 100 to 1000 mu m in average diameter.

Specifically, the present invention aims to provide a medical scaffold for in vivo implantation for tissue regeneration and the like.

In manufacturing the medical scaffold, the present invention uses a Fused Deposition Modeling (FDM) method among 3D printing methods. The FDM is a method in which the material is melted by heat and extruded through a nozzle at a constant pressure to form a laminate. The shape of the supplied material is in the form of a filament, which is continuously wound on a roll such as a protective cartridge or a thread. These solid materials are softened and extruded into a material close to the liquid phase through a temperature controlled head, which can be controlled by temperature, and then a three-dimensional model is formed through further fusion lamination. The feature of the FDM method is that the surface is rough and the precision is lower than that of other types of printers, but the advantage is that the raw material is cheap, the strength is strong, and the post-processing is easy.

As described above, the medical scaffold is implanted in vivo for the purpose of tissue regeneration, and the scaffold made of the biodegradable polymer can be mainly used for the bone tissue and cartilage tissue. In order to promote tissue regeneration, cells such as stem cells penetrate into the scaffold to adhere and proliferate and / or differentiate. In addition to the entry and exit of the cells, growth factors such as nutrients for their proliferation and / It is important that the supply of the material such as water is easy. Thus, it is preferred that the scaffold used therein has a size and shape suitable for the site to be implanted, as well as an appropriately sized open pore leading from the surface thereof to the interior. In the present invention, a scaffold is manufactured by printing in a 3D modeled form. The filament is based on a thermosetting biodegradable polymer and includes a foaming agent in a predetermined amount. And has a pore connecting from the surface to the inside through the decomposition of the foaming agent.

Specifically, in the method of manufacturing a scaffold according to the present invention, the first pores having a smaller size can be formed by gas release due to the decomposition of the foaming agent due to the temperature of the nozzle at the time of output. In the FDM type 3D printer used in the present invention, since resolution is easy to drive but resolution is not high, it may be difficult to realize small size pores such as the first pore through 3D modeling. On the other hand, the second pore of a larger scale can be formed by printer modeling.

For example, for use as a biologic alternative, the scaffold must meet a variety of essential properties, including 1) biodegradable and non-toxic, 2) structural stability, 3) low immunoreactivity, 4) ) Hydrophilic, and 6) biocompatibility. In the present invention, a chemical hydrolyzable biodegradable polymer was used to produce a medical scaffold satisfying this requirement.

Examples of the thermosetting biodegradable polymer include polybutylene succinate (PBS), polylactic acid (PLA), poly (butylene adipate-co-terephthalate) terephthalate (PBAT), polydioxanone, poly (? -hydroxybutyrate), poly (hydroxyvalerate), poly (? -capro T-CDM orthoester), poly (DTE carbonate), poly (methyl 2-cyanoacylate), poly (ε-caprolactone), polyglycolic acid, poly (p-methylphenoxy) (ethylglycineito) phosphazene] or poly (bis (p-carboxyphenoxy) propane-sebacic acid) may be used alone or in combination of two or more. .

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

Specifically, the thermosetting biodegradable polymer preferably has a heat capacity of 5 to 100 J / K in a molten state. When a polymer having a heat capacity of less than 5 J / K in a molten state is used, the viscosity is lowered in the molten state, which lowers the process speed, and the formation of pores in the polymer melt due to the gas release due to the decomposition of the foaming agent may be inhibited, If it exceeds 100 J / K, the heat transfer to the foaming agent is delayed due to the high heat absorption by the polymer, thereby inhibiting or delaying the decomposition of the microporous foaming agent from the inside of the scaffold, It may be difficult to form pores of the shape.

Furthermore, 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 less than 2.5 g / 10 min, the foaming efficiency of the foaming agent may be lowered due to the high viscosity. On the other hand, when the melt index of the polymer exceeds 30 g / 10 min, the viscosity of the polymer is too low and it may be difficult to maintain the pores formed by the blowing agent.

For example, the blowing agent may be a substance having a gas volume of 100 to 350 mL / g, which decomposes at a temperature higher than the decomposition temperature thereof, for example, at a printer nozzle temperature to release gas. When a foaming agent having a gas volume of less than 100 mL / g is used, it may be difficult to form a microstructure having a desired size and / or porosity. When a foaming agent having a gas volume of more than 350 mL / g is used, The size of the pore structure is increased more than necessary or the porosity is increased and the pore structure formed thereby can be easily collapsed.

Examples of the foaming agent include azodicarbonamide, modified azodicarbonamide, p-toluenesulfonyl semicarbazide, p-toluenesulfonyl hydrazide, but are not limited to, hydrazide, p-toluenesulfonyl acetone hydrazide, 5-phenyltetrazole, sodium bicarbonate, or combinations thereof . For example, the blowing agent may be a substance which decomposes at 130 to 250 ° C to generate gas, but is not limited thereto. Specifically, a foaming agent having a decomposition temperature at a low temperature of less than 130 ° C may be 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, a foaming agent having a decomposition temperature at a high temperature exceeding 250 ° C. may cause difficulty in foaming at a set nozzle temperature, or considerably increase the temperature of the nozzle for foaming. The modified azodicarbonamide may be a substance modified to further include a vinyl group so as to control the early foaming phenomenon during the foaming process, and may be a substance having a decomposition temperature controlled by such modification. For example, the azodicarbonamide is decomposed at 180 to 205 ° C, whereas the azodicarbonamide modified to have a vinyl group is decomposed at a lower temperature of 140 to 160 ° C.

For example, in the method of manufacturing a double pore scaffold according to the present invention, the filament used may include the foaming agent in an amount of 0.1 to 10 wt% based on the total weight of the filaments. If the content of the blowing agent in the filament is less than 0.1 wt%, it may be difficult to form fine pores having a desired size and / or porosity, for example, 100 μm. When the content of the blowing agent is more than 10 wt%, excessive pore formation It may be difficult to maintain the structure of the scaffold.

The temperature of the printer nozzle in the second step may be a temperature selected from the range of 180 to 230 ° C, but is not limited thereto. The higher the temperature of the nozzle, the more easily the decomposition of the blowing agent, thereby increasing the cumulative gas emission amount. However, 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 blowing agent can be selected at the same time.

The filament preferably has an average diameter of 1.7 to 1.8 mm, but is not limited thereto. However, the filament standard has been proposed in consideration of a method of using an FDM printer, and it is preferable that the filament has a diameter of about 1.75 mm to comply with the standard of a commercially available FDM 3D printer. However, it is apparent to those skilled in the art that when the specification of the apparatus is changed, the filament specification can be appropriately changed within the allowable tolerance range thereof.

In another aspect, the present invention provides a medical dual-pore scaffold fabricated by the above method.

As described above, the scaffolds produced by the method of the present invention have various sizes of pores that pass from the surface to the interior to facilitate entry and exit of cells and / or materials, and can be usefully used as implants for tissue regeneration .

A method for manufacturing a medical scaffold using a filament for a 3D printer prepared by mixing at a predetermined temperature so as to contain a foaming agent mixed with a polymer selected in consideration of a heat capacity in accordance with the present invention at a predetermined temperature, It is possible to provide a dual pore scaffold having pores of two different scales through a simple single-step process of outputting while maintaining the temperature at a certain level.

FIG. 1 is a schematic view illustrating a method of manufacturing a medical dual-pore scaffold by 3D printing using the expandable filament according to the present invention.
FIG. 2 is a graph showing the results of DSC analysis of polylactic acid as a biodegradable polymer according to the present invention and the foaming agent content of filaments containing azodicarbonamide as a foaming agent.
FIG. 3 is a graph showing the relationship between the amount of blowing agent in a scaffold prepared by outputting a polylactic acid as a biodegradable polymer according to the present invention and a filament containing azodicarbonamide as a blowing agent to a 3D printer, Fig. (c), (d), (e) and (f) show the cross section and the surface of the scaffold made of the filament with the blowing agent content of 1 wt% and the blowing agent content of 3 wt% and 5 wt% The cross section and the surface of a scaffold made of filaments are shown.
FIG. 4 is a graph showing FE-SEM analysis of pore formation characteristics according to the temperature of the 3D printer nozzle. Polylactic acid as a biodegradable polymer and filament containing 1 wt% of azodicarbonamide as a foaming agent were used. On the left side, the temperature of the nozzle was adjusted to 165 ° C lower than the decomposition temperature of the foaming agent and 205 ° C to the right, 1 shows a cross section of a scaffold.
Fig. 5 is a graph showing the FE-SEM analysis of the cross-sectional pore characteristics of a scaffold output in a bulk form using a polylactic acid as a biodegradable polymer and a filament containing 1 wt% of azodicarbonamide as a foaming agent .
6 is a view showing an example of a structure in which a macro pore pattern is formed by adjusting packing density through 3D printing modeling.
FIG. 7 shows the results of FE-SEM analysis of the surfaces of double pore scaffolds (denoted by D100, D80 and D60, respectively) prepared by adjusting packing density to 100%, 80% and 60% by 3D printing modeling . As a control, a PLA filament with a packing density of 100% (Neat PLA) was used.
FIG. 8 is a graph showing the FE-SEM analysis of a cross section of a double pore scaffold in which packing density is 100%, that is, a bulk type, through 3D printing modeling.
FIG. 9 is a graph showing the pore characteristics of the double pore scaffold fabricated by 3D printing according to the packing density, by the porosimetry (Hg-porosimetry) method using mercury penetration.
10 is a graph showing the results of DSC analysis according to the kind of the biodegradable polymer resin used in the expandable filament according to the present invention. Examples of the polymer resin include polyethylene (PE), polybutylene succinate (PBS), polylactic acid (PLA), and poly (butylene adipate-co- Poly (butylene adipate-co-terephthalate) (PBAT) was used.
11 is a graph showing the results of SEM analysis of a cross section of a bulk type scaffold produced by 3D printing PE, PBS, PLA and PBAT as biodegradable polymers and filament containing azodicarbonamide as a foaming agent.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for describing the present invention more specifically, and the scope of the present invention is not limited by these examples.

Example  1: Manufacture of expandable filaments for FDM 3D printers 1

99 g of polylactic acid (PLA) pellets and 1 g of azodicarbonamide (ADA) powder as a foaming agent were mixed and homogeneously blended at 180 rpm at 50 rpm using a single extruder Filaments for FDM 3D printers were produced (diameter: 1.75 mm).

Example  2: Manufacture of expandable filaments for FDM 3D printers 2

Filaments were 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: Manufacture of expandable filaments for FDM 3D printers 3

Filaments were 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: Manufacture of expandable filaments for FDM 3D printers 4

A filament was prepared in the same manner as in Example 3, except that modified azodicarbonamide (gold) was used to replace the azodicarbonamide as a foaming agent with a vinyl group.

Example  5: Manufacture of expandable filaments for FDM 3D printers 5

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

Experimental Example  1: Property analysis of filament

The filaments prepared according to Examples 1 to 5 were subjected to a tensile test according to ASTM D882. As a result, tensile strengths of 104.5 to 115.5 KPa in the MD direction and 137.9 to 152.1 KPa in the TD direction and 160% of the bank elongation were obtained.

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

Filaments prepared according to Examples 1 to 5 were supplied to an Edison Multi 3D printer (ROKIT) and output to produce a scaffold. At this time, the temperature of the 3D printer nozzle was kept at 205 deg. The output product was cooled and recovered without affecting the morphology.

Experimental Example  2: Depending on the type of foaming agent Scaffold  Property Analysis

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 The modified azodicarbonamide
(Example 9) Fine Yellow Powder 140 to 160 175-195 p-Toluenesulfonyl semicarbazide
(Example 10) Fine Yellow Powder 228 to 232 115 to 155

Experimental Example  3: Depending on the foaming agent content of the filament 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, the matrix polymer, such as increasing the amount of the blowing agent for a polymeric resin of the filaments (Examples 1 to 3 from a), due to the additives the glass transition temperature (T _g) and melting temperature (T _m) It was confirmed that the thermal properties were decreased, and further, the dispersity gradually increased as the content of the blowing agent was increased.

Experimental Example  4: Porosity printed in the form of monofilaments Scaffold  Cross section and surface analysis

The cross-sections and surfaces of the porous scaffolds printed in filament form according to Examples 6 to 8 were observed by FE-SEM, and the results are shown in Fig. As a result of analyzing the image of FIG. 3, it was confirmed that pores with a diameter of 45 to 220 μm were randomly formed in the printed scaffold. On the other hand, the printed monofilament type scaffold was found to have a diameter of about 450 μm. Further, from the surface images of the scaffolds prepared using filaments containing blowing agents at 1 wt%, 3 wt%, and 5 wt%, respectively, with respect to the polymers according to Examples 6 to 8, as the foaming agent content in the filaments increased, It was confirmed that the number of elongated pores was increased. It is an object of the present invention to provide a medical scaffold for use as an implant in vivo, and it is an important factor to have a suitable level of pores extending to the surface to facilitate entry and exit of the material and / or cells.

Comparative Example  1: by low temperature printing Scaffold  Produce

A scaffold was prepared in the same manner as in Example 6 except that the temperature of the nozzle was lowered to 165 deg. C lower than the decomposition temperature of the foaming agent.

Experimental Example 5: 3D  Characterization of Pore Formation by Printer Nozzle Temperature

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

Experimental Example  6: Bulk type Scaffold  Cross-sectional pore characterization analysis

The scaffold was manufactured in the same manner as in Example 6, and repeatedly carried out to produce a bulk type, not a monofilament type, and its cross section was analyzed by FE-SEM and the results are shown in FIG. As shown in FIG. 5, pores having a size of 60 to 210 μm were randomly formed in the interior, 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 uniformly blended at 180 rpm and 300 rpm using a single compressor to prepare filaments for an FDM 3D printer (diameter: 1.75 mm ).

The prepared filament was supplied to an Edison Multi 3D printer, and the nozzle temperature was maintained at 205 DEG C to produce a scaffold. At this time, a scaffold of macropores (10 mm x 10 mm) controlled by 3D printing modeling with fill densities of 100% (PLA03 D100), 80% (PLA03 D80) and 60% (PLA03 D60) × 3 mm). The output product was cooled and recovered without affecting the morphology.

Experimental Example  7: Filling  Double porosity 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. In addition, the surface morphology of the scaffolds of filling densities of 100%, 80% and 60% prepared with filaments containing a blowing agent according to Examples 11 to 13 was observed by FE-SEM. The results are shown in Fig. 7 . For comparative purposes, a scaffold with a packing density of 100% (Neat PLA) was prepared in the same manner using only commercially available PLA filaments containing only pure PLA, ie, a foaming agent. As shown in FIG. 7, when a commercial PLA filament was used, since it was produced at a packing density of 100%, not only macropores were present but also micropores revealed on the surface were not observed at all. 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 pattern and size realized according to the packing density controlled by 3D printing modeling, Showing microporous pores having micro-level pores connected to the surface and inside of the scaffold formed by the decomposition of the scaffold. For example, in the case of a sample having a packing density of 60% (PLAO3 D60), macropores having a size of 200 to 300 mu m implemented through 3D printing modeling were introduced. As confirmed by surface observation, Of the micropores. These micropores were formed in a similar pattern even at the filling densities of 100% and 80% regardless of the filling density.

As a representative example, a filament containing a foaming agent was supplied according to Example 11, and a bulk density scaffold output at a filling density of 100% was cut using liquid nitrogen, and its cross section was analyzed by SEM. The results are shown in Fig. When the filling density was set to 100%, macropores were not observed, and microscopic pores due to the gas generated by the decomposition of the blowing agent generated at the output were uniformly present in the scaffold.

Porosimetry using mercury penetration (Hg-porosimetry) was carried out to measure the porosity and the total penetration volume of the scaffolds according to the filling density, that is, the pore volume, and is shown in FIG. 9 and Table 2 below. As shown in Table 2, significantly higher porosity and total infiltration volume were exhibited in the scaffolds of Examples 11 to 13 compared to scaffolds output at a packing density of 100% using commercial PLA filaments, Of the total population. At this time, the bulk type scaffold made of the commercial PLA filament also showed some degree of porosity due to the porosity of the PLA itself. Further, as shown in Fig. 9, the scaffold made of the filament containing the blowing agent according to the present invention exhibited an additional peak at about 90 [mu] m added by the foaming agent together with the peak at about 30 [mu] m.

Name of sample 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: PBS-based foamable filament as 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: biodegradable polymer PBAT  Based foaming filament Scaffold  Produce

Except that poly (butylene adipate-co-terephthalate) (PBAT, EnPol PBG 7070, Lotte Fine Chemicals) was used instead of polylactic acid as the biodegradable polymer. A biodegradable porous scaffold was prepared in the same manner as in Example 11.

Comparative Example  2: biodegradable polymer PE  Based foaming filament 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: Property analysis of basic polymer resin

In order to produce a biodegradable polymer scaffold of desired porosity using a 3D printer, physical properties according to the type of the polymer resin as a basic material are analyzed first and compared with Table 3 below. These polymer resins were analyzed by differential scanning calorimetry (DSC), and the results are shown in FIG. As shown in the following Table 3, these polymer resins exhibited different heat capacities, glass transition temperature, melting point, density and / or melt flow index (MI). In order to confirm the effect of the physical properties of the polymer resin on the production of the porous scaffold, 3D printers including PBS, PLA, PBAT and PE according to Examples 1 to 3 and Comparative Example 1, And output to a 3D printer to produce a porous scaffold.

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

Experimental Example 9: 3D  The porosity produced by the printer Scaffold  Analysis of pore characteristics

According to Examples 11, 14 and 15 and Comparative Example 2, the cross-section of a porous scaffold prepared from filaments containing the same amount of azodicarbonamide as a foaming agent and containing PLA, PBS, PBAT and PE as basic polymers, SEM. The results are shown in Fig. According to Table 3, the heat capacity of the polymer resin was decreased in the order of PE> PBS> PLA> PBAT. Compared with FIG. 11, it is based on PBS, PLA and PBAT having a low heat capacity value of 100 J / K or less In the case of scaffolds, micropores 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 having a heat capacity value exceeding 100 J / K Despite being made of filaments containing the same type and content of foaming agent, only pore traces were observed but no distinct open channel pores were observed. It is considered that the reason is that the pores formed by the decomposition of the blowing agent at the time of output were collapsed by heat due to the high heat capacity of the polymer.

Further, the effect of the melt index on pore formation was confirmed. As shown in Table 3, the polymer resin used in the present invention exhibited a decreasing melt index in the order of PBS> PLA> PBAT> PE. It was confirmed from FIG. 3 that the higher the melting index, that is, the lower the viscosity, the higher the foaming efficiency.

Claims (12)

A first step of preparing a filament for 3D printing by blending a thermosetting biodegradable polymer and a foaming agent decomposed at a temperature equal to or higher than the melting point of the polymer at a decomposition temperature or lower of the foaming agent; And
And a second step of supplying the filament obtained from the first step to a Fused Deposition Modeling (FDM) 3D printer to output while maintaining the temperature of the printer nozzle at or above the decomposition temperature of the foaming agent.
A process for preparing a dual pore scaffold having a first pore having an average diameter of 10 to 100 μm and a second pore having an average diameter of 200 to 1000 μm.
The method according to claim 1,
Wherein the first pores are formed by decomposition of the foaming agent.
The method according to claim 1,
Wherein the second pores are formed by printer modeling.
The method according to claim 1,
The thermosetting biodegradable polymer may be selected from the group consisting of polybutylene succinate (PBS), polylactic acid (PLA), poly (butylene adipate-co-terephthalate) Poly (hydroxyvalerate), poly (ε-caprolactone), poly (ε-caprolactone), poly poly (ε-caprolactone), polyglycolic acid, poly (DETOSU-1,6HD-t-CDM orthoester), poly (DTE carbonate), poly (methyl 2-cyanoacylate) Methylphenoxy) (ethylglycineito) phosphazene], and poly (bis (p-carboxyphenoxy) propane-sebacic acid).
The method according to claim 1,
Wherein the thermosetting biodegradable polymer has a heat capacity of 5 to 100 J / K in a molten state.
The method according to claim 1,
Wherein the thermosetting biodegradable polymer has a melt flow index (MI) of 2.5 to 30 g / 10 min at 210 ° C.
The method according to claim 1,
Wherein the foaming agent is a substance having a gas volume of 100 to 350 mL / g, which is decomposed at a temperature not lower than its decomposition temperature to release gas.
The method according to claim 1,
The blowing agent may be selected from the group consisting of azodicarbonamide, modified azodicarbonamide, p-toluenesulfonyl semicarbazide, p-toluenesulfonyl hydrazide wherein the solvent is at least one selected from the group consisting of p-toluenesulfonyl acetone hydrazide, 5-phenyltetrazole, and sodium bicarbonate. .
The method according to claim 1,
Wherein the foaming agent is contained in an amount of 0.1 to 10 wt% based on the total weight of the filaments.
The method according to claim 1,
Wherein the filaments have an average diameter of 1.7 to 1.8 mm.
A medical dual-pore scaffold prepared by the method of any one of claims 1 to 10.
12. The method of claim 11,
Wherein the scaffold is an implant for tissue regeneration.

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