Scaffold for cartilage regeneration and construction method therefor

Abstract

The present invention relates to a scaffold for cartilage regeneration and a construction method therefor and, more specifically, to a scaffold for cartilage regeneration and a construction method therefor, wherein the scaffold is constructed by a scaffold construction device including a predetermined mold and structure, whereby the scaffold, even if produced in a large area, allows for excellent uniformity in the thickness of a biocompatible polymer sheet and in the pattern formed on the sheet, thus exhibiting excellent cartilage regeneration effects and adhesion to the affected area.

Description

Scaffold for cartilage regeneration and method for manufacturing the same

[0001] The present invention relates to a support for cartilage regeneration and a method for manufacturing the same.

[0002] Cartilage is a bone tissue composed of chondrocytes and the surrounding cartilaginous matrix. Chondrocytes function to synthesize and secrete the cartilaginous matrix within the cartilage. The cartilaginous matrix provides elasticity to the cartilage. Unlike other tissues, cartilage lacks blood vessels and nerves, making it difficult to regenerate once damaged. Due to this insufficient self-repair capacity, surgical procedures such as microfracture are required to treat cartilage damage.

[0003] Microfracture surgery is a surgical technique that regenerates damaged cartilage. It creates microscopic fractures in the exposed bone due to damaged cartilage, and when the subchondral bone is damaged, bone marrow components including bone marrow stem cells leak out, and these cells differentiate to form cartilage.

[0004] Most cartilage produced by microfracture is fibrocartilage, not hyaline cartilage. Fibrocartilage is rich in type I collagen and has low proteoglycan content, making it less resistant to wear. Therefore, when damaged cartilage tissue regenerates into fibrocartilage, symptoms improve by 60-70% for about two years after surgery. However, after that, structural collapse may occur, leading to worsening symptoms. Furthermore, the larger the defect, the more severe the symptom worsens. Microfracture treatment has limitations in treating extensive cartilage defects and has the disadvantage of regenerating fibrocartilage with poor mechanical properties. Therefore, it is necessary to implant a cartilage regeneration scaffold into the cartilage defect along with microfracture treatment to promote cartilage regeneration and enhance maturation during the cartilage regeneration process.

[0005] Cartilage regeneration scaffolds must be uniform in thickness and pattern to ensure dense and consistent growth of chondrocytes. However, existing methods have limitations in achieving uniform thickness and pattern. In particular, when cartilage regeneration scaffolds are manufactured to a surface area exceeding a certain size, non-uniformity in thickness and pattern increases.

[0006]

[0007] The purpose of the present invention is to provide a support for cartilage regeneration having a uniform thickness and pattern and a method for manufacturing the same.

[0008] The purpose of the present invention is to provide a support for cartilage regeneration that can be attached to a cartilage defect site with high adhesive strength and a method for manufacturing the same.

[0009]

[0010] 1. A scaffold for cartilage regeneration, which is made of a biocompatible polymer and has a pattern for cartilage regeneration formed on one side or both sides, the pattern is made of repeating crests and valleys, and the area of ​​the pattern satisfying the uniformity (U) of the following mathematical formula 1 is 95% or more of the total area:

[0011] [Mathematical Formula 1]

[0012] U = |H P1 - H P2 |≤ 0.1H n

[0013] (In the equation, H P1 is the height at P1, H P2 refers to the height at P2 and H n refers to the height difference between the peak and valley of the normal pattern).

[0014] 2. In the above 1, a support for cartilage regeneration, wherein both P1 and P2 are points located on the floor or both are located on the bone.

[0015] 3. A support for cartilage regeneration, wherein the area satisfying the uniformity of mathematical expression 1 in the above 1 is 99% or more of the total area.

[0016] 4. In the above 1, a support for cartilage regeneration having a thickness of 30 to 100 ㎛.

[0017] 5. A support for cartilage regeneration, wherein in the above 1, the biocompatible polymer is any one selected from the group consisting of polycaprolactone, polylactide-co-glycolide, polyethylene glycol, polyethylene oxide, polylactic acid, and polyglycolic acid.

[0018] 6. A support for cartilage regeneration in the above 1, wherein the biocompatible polymer is polylactide-co-glycolide containing 65 to 85 mol% of lactide and 15 to 35 mol% of glycolide.

[0019] 7. In the above 1, the pattern is a straight or curved shape in which the floor and the valley are repeated in parallel, a support for cartilage regeneration.

[0020] 8. A support for cartilage regeneration, wherein any one selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs is applied to one or both sides of the support in the above 1.

[0021] 9. A support for cartilage regeneration in the above 1, with fibrin applied to the edge.

[0022] 10. A method for producing a support for cartilage regeneration according to any one of items 1 to 9 above, comprising: applying a polymer solution containing a biocompatible polymer onto a polyurethane acrylate mold to produce a sheet-shaped semi-hardened material; applying pressure to the semi-hardened material with a polydimethylsiloxane mold to produce a patterned semi-hardened material; and drying the patterned semi-hardened material.

[0023] 11. A method for manufacturing a support for cartilage regeneration, wherein in the above 10, the patterned semi-hardened material is manufactured by placing the semi-hardened material between a polyurethane acrylate mold and a polydimethylsiloxane mold and then applying pressure with upper and lower plates.

[0024] 12. A method for manufacturing a support for cartilage regeneration, wherein in the above 10, the polyurethane acrylate mold or the polydimethylsiloxane mold has unevenness formed for pattern formation.

[0025] 13. A method for manufacturing a support for cartilage regeneration, wherein the upper plate in the above 11 has a pressure rod and a guide rod.

[0026] 14. A method for manufacturing a support for cartilage regeneration, wherein the pressure in the above 10 is 0.40 Pa to 0.70 Pa.

[0027]

[0028] The support for cartilage regeneration of the present invention has an excellent cartilage regeneration effect.

[0029] The support for cartilage regeneration of the present invention has excellent adhesive strength.

[0030] The support for cartilage regeneration of the present invention has excellent workability.

[0031]

[0032] Figure 1 is a conceptual diagram of a manufacturing process of a support for cartilage regeneration of the present invention.

[0033] Figure 2 schematically illustrates a method for measuring the uniformity (U) of mathematical expression 1.

[0034] Figure 3 is a perspective view of a device for manufacturing a support for cartilage regeneration according to one embodiment of the present invention.

[0035] Figure 4 is a front view of a support manufacturing device for cartilage regeneration according to one embodiment of the present invention.

[0036] Figure 5 is a top view of a support manufacturing device for cartilage regeneration according to one embodiment of the present invention.

[0037] Fig. 6 is a cross-sectional view taken along A1-A2 of Fig. 5.

[0038] Figure 7 is a block diagram illustrating a device for manufacturing a support for cartilage regeneration according to an embodiment of the present invention.

[0039] Figure 8 is a plan view showing the shape of a pressurizing plate of a pressurizing unit according to an embodiment of the present invention.

[0040] FIG. 9 is a plan view showing another shape of a pressurizing plate of a pressurizing unit according to an embodiment of the present invention.

[0041] FIG. 10 is a plan view showing another shape of a pressurizing plate of a pressurizing unit according to an embodiment of the present invention.

[0042] Figure 11 is a flowchart illustrating a method for manufacturing a support for cartilage regeneration using a support manufacturing device for cartilage regeneration according to one embodiment of the present invention.

[0043] Figures 12 to 14 are flowcharts of a detailed method for manufacturing a support for cartilage regeneration according to each step of Figure 11.

[0044] Figures 15 to 20 are process diagrams illustrating a method for manufacturing a support for cartilage regeneration using a support manufacturing device for cartilage regeneration according to one embodiment of the present invention.

[0045] Figure 21 is a photograph of a large-area PLGA sheet according to an embodiment of the present invention.

[0046] Figure 22 is a photograph of the thickness measurement of a large-area PLGA sheet of an embodiment of the present invention.

[0047] Figure 23 is a photograph of a pattern measurement between a valley and a peak of a large-area PLGA sheet of an embodiment of the present invention.

[0048]

[0049] The present invention provides a support for cartilage regeneration and a method for manufacturing the same.

[0050] The present invention provides a cartilage regeneration support having excellent cartilage regeneration effect and excellent adhesion to a diseased area, and a method for manufacturing the same, by manufacturing the support using a support manufacturing device including a predetermined mold and structure, so that even when produced on a large area, the uniformity of the thickness of a biocompatible polymer sheet and the uniformity of the pattern formed on the sheet are excellent.

[0051] The present invention provides a support for cartilage regeneration, which is made of a biocompatible polymer, has a pattern formed on one side or both sides for cartilage cell growth, the pattern is made of repeating crests and valleys, and the area of ​​the pattern satisfying the uniformity (U) of the following mathematical formula 1 is 95% or more of the total area:

[0052] [Mathematical Formula 1]

[0053] U = |H P1 - H P2 |≤ 0.1H n

[0054] (In the above equation, H P1 is the height at P1, H P2 refers to the height at P2 and H n refers to the height difference between the peak and valley of the normal pattern).

[0055] The cartilage regeneration support of the present invention has a high uniformity despite its thin thickness and an appropriate elongation and tensile strength as a support for cartilage regeneration, thereby exhibiting an excellent cartilage regeneration effect and excellent adhesion to the affected area.

[0056] The support for cartilage regeneration of the present invention is made of a biocompatible polymer.

[0057] Biocompatible polymers are not limited to being made of a specific material. For example, they may be any one selected from the group consisting of polylactide-co-glycolide (PLGA), polycaprolactone (PCL), polyethylene glycol (PEG), polyethylene oxide (PEO), polylactic acid (PLA), and polyglycolic acid (PGA).

[0058] When the scaffold for cartilage regeneration is composed of polylactide-co-glycolide or polycaprolactone, it is preferable in terms of uniformity and physical properties (elongation, tensile strength, etc.). For achieving the purpose of the present invention, it is more preferable to be composed of PLGA containing LA (Lactide) monomer and GA (Glycolide) monomer in a molar ratio of 65 to 85 to 35 to 15.

[0059] The biocompatible polymer of the present invention has a pattern formed on one side or both sides for cartilage cell growth.

[0060] When a cartilage regeneration support is attached to the affected area, chondrocytes existing around the support grow along the bone of the pattern, inducing regeneration of the damaged cartilage.

[0061] Patterns can be formed on either one side or both sides. To facilitate differentiation between the upper and lower surfaces of the cartilage regeneration scaffold, patterns can be formed on only the upper or lower surfaces. Furthermore, if the cartilage regeneration scaffold is small, patterns can be formed on both sides, eliminating the need for distinction between the upper and lower surfaces.

[0062] The pattern is not limited to a specific shape, as long as it has repeating peaks and valleys. For example, the pattern can be a straight or curved shape with parallel peaks and valleys. The pattern can be formed as a straight line parallel to one edge of the cartilage regeneration scaffold, a diagonal line at a predetermined angle to one edge, or a wavy curve.

[0063] The vertex refers to the relatively protruding part, and the groove refers to the relatively depressed part between the vertices. Cartilage cells grow along the groove between the vertices.

[0064] The width between the floors can be designed in various ways, for example, 600 to 1000 nm, 700 to 1000 nm, 800 to 1000 nm, 600 to 900 nm, 600 to 800 nm, 600 to 700 nm, etc.

[0065] The width between the grooves can also be designed to be the same as the width between the floors.

[0066] The height difference between the peak and the valley (the height of the peak relative to the valley) can be designed in various ways, such as 600 to 1000 nm, 700 to 1000 nm, 800 to 1000 nm, 600 to 900 nm, 600 to 800 nm, and 600 to 700 nm.

[0067] The distance between the peaks of the pattern, the distance between the valleys, and the height difference between the peaks and valleys may be the same or different. When they are different, the difference may be 100 nm or less, 90 nm or less, 80 nm or less, 70 nm or less, 60 nm or less, or 50 nm or less, respectively.

[0068] For example, the distance between crests, the distance between valleys, and the height difference between crests and valleys can be equal to 800 nm, 700 nm, or 600 nm, respectively. In addition, the distance between crests and the distance between valleys can be 800 nm, and the height difference between crests and valleys can be 750 nm or 850 nm. In addition, the distance between crests and the distance between valleys can be 700 nm, and the height difference between crests and valleys can be 650 nm or 750 nm.

[0069] The distance between the peaks of the pattern, the distance between the valleys, and the height difference between the peaks and valleys can be changed by adjusting the size and spacing of the pattern formed in the mold used for manufacturing the support for cartilage regeneration.

[0070] The pattern is an area that satisfies the uniformity (U) of the following mathematical expression 1, which is 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 99.9% or more of the total area.

[0071] [Mathematical Formula 1]

[0072] U = |H P1 - H P2 |≤ 0.1H n

[0073] In the above equation, H P1 is the height at P1, H P2 refers to the height at P2 and H n refers to the height difference between the peak and valley of a normal pattern.

[0074] P1 and P2 are both arbitrary points on the floor of the pattern or both are arbitrary points on the valley of the pattern.

[0075] For example, P1 and P2 may be points on the same floor. P1 may be a point on a floor, and P2 may be a point on another floor adjacent to that floor, that is, across a valley to the left or right of that floor. Alternatively, P1 may be a point on a floor, and P2 may be a point on another floor spaced apart from that floor, that is, across multiple valleys to the left or right of that floor.

[0076] H P1 is the height at P1. The height at P1 means the height from the valley to any point on the crest, P1. If the crest is formed at the intended height, H P1 is the same height as the pattern formed in the mold, and H is the difference in height between the peak and valley of the normal pattern. n Same as H. If pattern formation is poor, P1 The height of the pattern formed in the silver mold is different.

[0077] H P2 refers to the height at P2. H P1 It is the same as .

[0078] The support for cartilage regeneration of the present invention has a height difference between P1 and P2 equal to the height difference between the peak and the bone of the normal pattern (H n) is 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less.

[0079] If the thickness and pattern of the cartilage regeneration scaffold are uniform, chondrocyte proliferation will occur smoothly along the uniform pattern, resulting in excellent cartilage regeneration effects. However, if the pattern is not uniform and there are partially damaged areas, cell proliferation may be halted in the damaged areas.

[0080] When P1 and P2 are points on the same floor, when measuring the uniformity of the pattern, the height difference between P3 and P4, which are arbitrary points on the valley of the pattern, can optionally be additionally considered.

[0081] P3 and P4 can be points on the same bone. P3 can be a point on a bone, and P4 can be a point on another bone adjacent to that bone, that is, across a crest to the left or right of that bone. P3 can also be a point on a bone, and P4 can be a point on another bone separate from that bone, that is, across multiple crests to the left or right of that bone.

[0082] When P1 and P2 are arbitrary points on the floor and P3 and P4 are arbitrary points on the valley, U1 = |H P1 - H P2 |≤ 0.1H n and U2= |H P3 - H P4 |≤ 0.1H n (H P3 is the height at P3, H P4 refers to the height at P4 and H n The area satisfying the height difference between the peak and valley of the normal pattern may be 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, 99.5% or more, or 99.9% or more of the total area.

[0083] The thickness of the scaffold for cartilage regeneration may be 30 to 100 μm, preferably 40 to 70 μm, and more preferably 50 to 60 μm. If the thickness is thinner than 30 μm, the mechanical strength (tensile strength and compressive strength) is low, so the scaffold or the nano-pattern formed on the scaffold is easily damaged. If the thickness is thicker than 100 μm, the adhesive strength is low, making it difficult for the scaffold to remain attached to the cartilage for a sufficient period of time required for cartilage regeneration.

[0084] The tensile strength of the scaffold for cartilage regeneration may be 3 to 8 MPa, preferably 4 to 6 MPa. The elongation of the scaffold for cartilage regeneration may be 4 to 10%, preferably 5 to 7%. If the tensile strength is less than 3 MPa or the elongation is more than 10%, the scaffold is prone to deformation and difficult to handle, and the patient may feel discomfort after the procedure. If the tensile strength is more than 8 MPa or the elongation is less than 4%, the scaffold is susceptible to breakage and may lack flexibility, which may cause problems with proper attachment to the cartilage.

[0085] The adhesion strength of the scaffold for cartilage regeneration is 0.2 to 0.5 N / cm. 2 may be, preferably 0.3 to 0.4 N / cm 2 It could be.

[0086] A cross-section or both sides of a cartilage regeneration scaffold may be coated with one or more selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs. The factors coated on the scaffold can enhance the rate of cartilage regeneration by promoting cell growth.

[0087] The edges of the cartilage regeneration scaffold may be coated with fibrin. The fibrin applied to the edges can form fibrous clots, acting as bridges for cell migration. This facilitates cell migration and proliferation in the damaged cartilage area, thereby enhancing the rate of cartilage regeneration.

[0088] A scaffold for cartilage regeneration can be manufactured by a method including the steps of: applying a polymer solution containing a biocompatible polymer and an organic solvent onto a polyurethane acrylate (PUA) mold to manufacture a sheet-shaped semi-cured material; applying pressure to the semi-cured material with a polydimethylsiloxane (PDMS) mold to manufacture a patterned semi-cured material; and drying the patterned semi-cured material.

[0089] A scaffold for cartilage regeneration can be manufactured by a method including: applying a polymer solution containing a biocompatible polymer and an organic solvent onto a polyurethane acrylate (PUA) mold to manufacture a sheet-shaped semi-cured material; positioning the semi-cured material between a polyurethane acrylate (PUA) mold and a polydimethylsiloxane (PDMS) mold and then applying pressure with upper and lower plates to manufacture a patterned semi-cured material; and drying the patterned semi-cured material.

[0090] A polyurethane acrylate (PUA) mold and / or a polydimethylsiloxane (PDMS) mold has a protrusion formed on one side and / or both sides of the support to form a pattern.

[0091] More specifically, a scaffold for cartilage regeneration can be manufactured by a method including the following steps: a semi-hardened material forming step (S100), a semi-hardened material fixing step (S200), a transporting step (S300), a pressurizing step (S400), a drying step (S500), and a separation step (S600).

[0092] Referring to FIGS. 12 and 15(A), the semi-hardened mold forming step (S100) may include a step (S110) of placing an upper mold (900) on a base surface. The base may be the ground, a structure having a flat surface, or a lower plate (510). When the base surface is the lower plate (510), the lower plate (510) may be placed on the loading area (LA). In this embodiment, a case where the base is the lower plate (510) will be illustrated and described.

[0093] The upper mold (900) is a polyurethane acrylate (PUA) mold.

[0094] The upper mold (900) may include a first pattern surface (910) on which a pattern is formed, and a first support surface (960) disposed on the opposite surface of the first pattern surface (910). The first support surface (960) may be placed on the base surface.

[0095] The first pattern surface (910) may include a pattern of a predetermined shape. The pattern is not limited to a specific shape as long as it has repeating peaks and valleys. For example, the pattern may be a straight or curved shape with repeating peaks and valleys parallel to each other. The shape of the pattern may be a straight line parallel to one edge of the cartilage regeneration support, a diagonal line forming a predetermined angle with one edge, a wavy curve, etc.

[0096] The width between the floors can be designed in various ways to suit the pattern of the scaffold for cartilage regeneration to be manufactured, such as 600 to 1000 nm, 700 to 1000 nm, 800 to 1000 nm, 600 to 900 nm, 600 to 800 nm, 600 to 700 nm, etc.

[0097] The width between the grooves can also be designed to be the same as the width between the floors.

[0098] The height difference between the peak and the valley (the height of the peak based on the valley) can be designed in various ways to suit the pattern of the cartilage regeneration support to be manufactured, such as 600 to 1000 nm, 700 to 1000 nm, 800 to 1000 nm, 600 to 900 nm, 600 to 800 nm, and 600 to 700 nm.

[0099] The distance between the peaks of the pattern, the distance between the valleys, and the height difference between the peaks and valleys may be the same or different. When they are different, the difference may be 100 nm or less, 90 nm or less, 80 nm or less, 70 nm or less, 60 nm or less, or 50 nm or less, respectively.

[0100] For example, the distance between crests, the distance between valleys, and the height difference between crests and valleys can be equal to 800 nm, 700 nm, or 600 nm, respectively. In addition, the distance between crests and the distance between valleys can be 800 nm, and the height difference between crests and valleys can be 750 nm or 850 nm. In addition, the distance between crests and the distance between valleys can be 700 nm, and the height difference between crests and valleys can be 650 nm or 750 nm.

[0101] The size and spacing of the pattern of the cartilage regeneration scaffold manufactured can be changed by controlling the size and spacing of the pattern formed in the mold.

[0102] Referring to FIG. 12 and FIG. 15(B), the step (S100) of forming a semi-hardened article (1000b) may include a step (S120) of applying a biocompatible polymer solution (1000a) to the first pattern surface (910) of the upper mold (900). By applying the biocompatible polymer solution (1000a) to the PUA mold (upper mold, 900), a sheet-shaped semi-hardened article (1000b) can be formed.

[0103] A biocompatible polymer solution can be prepared by mixing a biocompatible polymer and an organic solvent, and the organic solvent can be, for example, a halomethane solvent such as chloroform or dichloroform.

[0104] The suitable concentration of the biocompatible polymer solution may vary depending on the type of the biocompatible polymer, and for example, the concentration of the biocompatible polymer in the biocompatible polymer solution may be 15% (w / w) to 24% (w / w). When the biocompatible polymer is PLGA, the concentration may be 15% (w / w) to 21% (w / w), and when the biocompatible polymer is PCL, the concentration may be 18% (w / w) to 24% (w / w).

[0105] In the process of applying the biocompatible polymer solution (1000a), some of the solvent evaporates at room temperature to form a sheet-like semi-cured article (1000b), which prevents the semi-cured article from flowing out even when the upper mold (900) is turned over.

[0106] In this way, the upper mold (900) on which the semi-hardened material (1000b) is placed on the first pattern surface (910) is referred to as the first mold (1100).

[0107] Since the first mold (1100) is placed on the upper mold (900) with a semi-hardened material (1000b), the first mold (1100) must be turned over later and brought into contact with the lower mold (800).

[0108] Therefore, in order to bring the surface of the exposed semi-hardened material (1000b) into contact with the lower mold (800) by turning over the first mold (1100), a high viscosity biocompatible polymer can be used or a high volatility solvent can be used to quickly evaporate the solvent, thereby increasing the viscosity of the semi-hardened material (1000b) and preventing it from flowing down.

[0109] Referring to FIG. 11, the method for manufacturing a support for cartilage regeneration of the present invention may include a step (S200) of fixing a semi-hardened material (1000b). Fixing the semi-hardened material (1000b) is a step of inverting the first mold (1100) and bringing the exposed semi-hardened material (1000b) into contact with the lower mold (800). The mold formed by bringing the lower mold (800) into contact with the first mold (1100) is referred to as a second mold (1200).

[0110] The lower mold (800) is a polydimethylsiloxane (PDMS) mold.

[0111] Referring to FIG. 13 and FIG. 16(A), the step (S200) of fixing the semi-cargo (1000b) may include a step (S210) of placing the carrier (320) on the loading area (LA).

[0112] A lower plate (510) may be placed on a carrier (320). For example, the lower plate lower surface (512) may be placed on the carrier mounting surface (328). Accordingly, the lower plate (510) may be placed on the loading area (LA) such that the upper surface (517) of the lower plate is exposed.

[0113] Referring to FIG. 13 and FIG. 16(B), the step (S200) of fixing the semi-hardened material (1000b) may include a step (S220) of placing the lower mold (800) on the lower plate (510). For example, the lower mold (800) may be placed on the upper surface (517) of the lower plate on the loading area (LA).

[0114] The lower mold (800) may include a flat surface without a pattern and a second support surface (860) formed on the opposite surface of the flat surface. The second support surface (860) may be placed on the upper surface (517) of the lower plate. Therefore, when the lower mold (800) is placed on the lower plate (510) in the loading area (LA), the flat surface may be exposed to the outside. The lower mold (800) having a flat surface without a pattern is used when manufacturing a scaffold for cross-sectional nano-patterned cartilage regeneration.

[0115] The lower mold (800) may include a second pattern surface (810) and a second support surface (860) formed on the opposite side of the second pattern surface (810). The second pattern surface (810) may be a flat surface without a pattern or a surface with a pattern formed thereon. If it is a flat surface without a pattern, it is used when manufacturing a single-sided pattern cartilage regeneration support, and if it is a surface with a pattern formed thereon, it is used when manufacturing a double-sided pattern cartilage regeneration support. The second support surface (860) may be placed on the upper surface (517) of the lower plate. Therefore, when the lower mold (800) is placed on the lower plate (510) on the loading area (LA), the second pattern surface (810) may be exposed to the outside.

[0116] Referring to FIGS. 13 and 16(C), the step (S200) of fixing the semi-hardened material (1000b) may include a step (S230) of contacting the first mold (1100) with the lower mold (800). For example, the semi-hardened material (1000b) may be fixed by placing the first mold (1100) so that it contacts the second pattern surface (810).

[0117] The step (S200) of fixing the semi-conductor (1000b) can expose the first support surface (960) of the upper mold (900) to the outside on the loading area (LA).

[0118] Referring to FIGS. 11 and 17, a method for manufacturing a support for cartilage regeneration according to one embodiment of the present invention may include a transfer step (S300) of transferring a second mold (1200).

[0119] The transfer step (S300) can move the second mold (1200) placed on the loading area (LA) to the molding area (PA).

[0120] A pressing plate (430) of a pressing unit (400) may be placed above the forming area (PA). An upper plate (520) may be coupled to the pressing plate (430). Accordingly, the second mold (1200) may be placed below the upper plate (520).

[0121] For example, the pressure plate (430) may include a pressure plate lower surface (432) and a pressure plate upper surface (437). An upper plate (520) may be coupled to the pressure plate lower surface (432).

[0122] The upper plate (520) may include an upper plate pressure surface (522) and an upper plate coupling surface (527). A pressure plate lower surface (432) may be coupled to the upper plate coupling surface (527). In addition, a pressure distribution member (550) may be bonded to the upper plate pressure surface (522).

[0123] At the bottom of the forming area (PA), a second mold (1200) may be moved, and a transfer unit (300) for moving the second mold (1200) and a lower plate (510) placed on the transfer unit (300) may be placed.

[0124] For example, the transport unit (300) may include a transport rail (310) and a carrier (320). A lower plate (510) may be placed on the carrier (320). A second mold (1200) may be placed on the lower plate (510). Accordingly, the second mold (1200) may be placed in the forming area (PA).

[0125] And the transport unit (300) may further include a transport drive unit (330) capable of moving the carrier (320). By driving the transport drive unit (330), the carrier (320) may be moved from the loading area (LA) to the forming area (PA).

[0126] Accordingly, in the forming area (PA), the second mold (1200) may be placed in the lower direction of the pressure distribution unit (550). For example, in the transfer step (S300), the pressure distribution unit (550) and the first support surface (960), which is the exposed surface of the second mold (1200), may be placed in the forming area (PA) so that they face each other.

[0127] Referring to FIG. 11, a method for manufacturing a support for cartilage regeneration according to one embodiment of the present invention may include a pressurizing step (S400) of pressurizing a fixed semi-hardened material (1000b).

[0128] For example, referring to FIG. 14 and FIG. 18(A), the pressurizing step (S400) can be performed in the forming area (PA).

[0129] The pressurizing step (S400) of pressurizing the fixed semi-hardened material (1000b) may include a step (S410) of contacting the upper plate (520) with the second mold (1200). For example, the upper plate pressurizing surface (522) of the upper plate (520) may be contacted with the first support surface (960) of the upper mold (900). As a specific example, the step (S410) of contacting the upper plate (520) may contact the pressure distribution unit (550) with the first support surface (960).

[0130] In the step (S410) of bringing the upper plate (520) into contact with the second mold (1200), a step of operating the pressurizing unit (400) may be included. For example, the pressurizing unit (400) may operate an actuator disposed in the pressurizing unit body (410). A pressurizing rod (420) may be connected to the actuator. The pressurizing rod (420) may be moved toward the pressurizing plate (430). The pressurizing rod (420) may be mounted on a mounting portion (439) disposed on one surface of the pressurizing plate (430).

[0131] The pressurizing rod (420) can move in the vertical direction. When the pressurizing rod (420) moves downward, the upper plate (520) coupled to the pressurizing plate (430) can move downward. Accordingly, the upper plate (520) can move toward the lower plate (510).

[0132] The upper plate (520) can be moved to bring the upper plate pressure surface (522) into contact with the second mold (1200) placed on the lower plate (510). More specifically, the pressure distribution unit (550) can be brought into contact with the first support surface (960) of the upper mold (900) exposed in the second mold (1200).

[0133] In the step (S410) of contacting the upper plate (520) with the second mold (1200), the thickness of some areas of the second mold (1200) may be different from that of other areas.

[0134] For example, during the application process of the biocompatible polymer solution (1000a), the thickness difference may occur due to the biocompatible polymer solution (1000a) being unevenly distributed. Alternatively, the thickness difference may occur due to the formation thickness of the upper mold (900) and the lower mold (800).

[0135] When the above thickness difference occurs, the upper plate (520) may tilt, and the front surface (Whole surface) of the pressure distribution unit (550) and the front surface (Whole surface) of the first support surface (960) may not make surface contact.

[0136] Referring to FIG. 14 and FIG. 18(B), the pressurizing step (S400) may include a step (S420) of adjusting the inclination of the upper plate (520).

[0137] The step of adjusting the inclination (S420) may allow the upper plate (520) and the fixed semi-hardened material (1200) to be in surface contact. For example, the step of adjusting the inclination of the upper plate (520) (S420) may allow the front surface (Whole surface) of the pressure distribution unit (550) and the front surface (Whole surface) of the first support surface (960) to be in surface contact.

[0138] After the above two configurations are brought into contact, a step of leveling the upper plate (520) can be performed. That is, the upper plate (520) can be rotated (the inclination adjusted).

[0139] The inclination of the upper plate (520) can be adjusted through the gimbal unit (450). The gimbal unit (450) can be placed on the upper surface of the pressure plate (430). For example, the gimbal unit (450) can be placed between the guide rod (440) formed in the pressure unit (400) and the pressure plate (430). In addition, the gimbal unit (450) can be placed between the mounting unit (439) and the pressure plate (430).

[0140] If the inclination of the upper plate (520) is not horizontal, the gimbal unit (450) can rotate the upper plate (520) to level the upper plate (520).

[0141] Accordingly, the gimbal unit (450) can provide the load of the upper plate (520) to the region where the thickness difference occurs in the second mold (1200). For example, the gimbal unit (450) can provide the load to the region where the thickness difference occurs by rotating (tilting) the upper plate (520) to level it. Here, since the upper plate (520) is coupled to the pressure plate (430), the loads of the upper plate (520) and the pressure plate (430) can be provided to the second mold (1200).

[0142] The load of the upper plate (520) and the pressure plate (430) provided to the second mold (1200) can provide pressure to the fixed semi-hardened body (1200). Therefore, the load of the upper plate (520) and the pressure plate (430) can pressurize the fixed semi-hardened body (1000b) in the region where the thickness difference occurs.

[0143] When the level of the upper plate (520) is formed, the gimbal part (450) can stop providing a load to the second mold (1200).

[0144] Referring to FIG. 14 and FIG. 19, a step (S430) of maintaining a pressure on a pressure plate (430) may be included.

[0145] The step of maintaining the pressure (S430) can be performed in a state where the pressure distribution unit (550) and the first support surface (960) are in surface contact and the upper plate (520) is horizontal.

[0146] In the aforementioned state, the target pressing force can be maintained on the pressing plate (430). The step of maintaining the pressing force (S430) can provide the pressing force of 0.40 Pa to 0.70 Pa, preferably 0.45 to 0.65 MPa, to the pressing plate (430). The pressing force providing time can vary depending on the magnitude of the pressing force, and can be provided for a holding time of, for example, 30 to 50 minutes.

[0147] The target pressing force provided to the pressing plate (430) can be transmitted to the upper plate (520). The pressing force transmitted to the upper plate (520) can be provided to the second mold (1200) through the upper plate pressing surface (522). The pressing force provided to the second mold (1200) can be transmitted to the fixed semi-hardened material (1200).

[0148] The pattern shape formed on the first pattern surface (910) and the second pattern surface (810) can be transferred to the semi-hardened material (1000b) through the pressure applied to the second mold (1200).

[0149] Referring to FIG. 11 and FIG. 20, a drying step (S500) for drying a semi-hardened material (1000b) may be included.

[0150] The drying step (S500) can provide target drying heat to the second mold (1200) through the lower plate (510). Alternatively, the second mold (1200) can be dried in a dry oven or hot plate, thereby drying the semi-hardened article (1000b).

[0151] When drying the second mold (1200) through the lower plate (510), a heating plate may be provided inside the lower plate (510). The heating plate may transmit thermal energy to the upper surface (517) of the lower plate to dry the second mold (1200). The thermal energy transmitted to the second mold (1200) may be transmitted to the semi-hardened article (1000b) to dry the semi-hardened article (1000b).

[0152] Meanwhile, when drying the second mold (1200) in a dry oven, the carrier (320) can be moved from the forming area (PA) to the loading area (LA), and the second mold (1200) loaded on the lower plate (510) can be unloaded from the loading area (LA). The second mold (1200) can be unloaded and loaded into the dry oven (DO), and the drying heat can be provided to the second mold (1200).

[0153] The drying step (S500) here can provide thermal energy of 15°C to 45°C to the second mold (1200) for 6 to 10 hours.

[0154] Alternatively, the drying step (S500) may be performed by placing the second mold (1200) on a hot plate to dry it. When using a hot plate, a steel plate weighing 0.5 kg to 2 kg may be laminated on the second mold (1200), and the hot plate may be heated to 60°C to 80°C to dry the second mold (1200). The second mold (1200) may be dried by maintaining the heating temperature for 4 to 8 hours.

[0155] Here, the steel plate can prevent the upper mold (900) or the lower mold (800) from being separated from the semi-hardened material (1000b) during the drying process.

[0156] If the upper mold (900) or the lower mold (800) is separated during the drying process, the surface pattern of the semi-hardened article (1000b) may be damaged. Therefore, the drying process may be performed by placing the steel plate on the second mold (1200) to prevent damage to the surface pattern of the semi-hardened article (1000b).

[0157] In this way, the second mold (1200) can be dried to form a hardened cartilage regeneration support (1000) between the upper mold (900) and the lower mold (800).

[0158] Referring to FIG. 11 and FIG. 20, a step (S600) of separating a support for cartilage regeneration (1000) from a second mold (1200) can be performed.

[0159] The cartilage regeneration support (1000) formed between the lower mold (800) and the upper mold (900) constituting the second mold (1200) can be separated from the lower mold (800) and the upper mold (900).

[0160] After the separation step (S600), the biosupport (1000) can be immersed in 70% ethanol for 10 seconds and washed with purified water.

[0161] The method for manufacturing a support for cartilage regeneration of the present invention can be performed using the following cartilage regeneration support manufacturing device (10). Hereinafter, the support manufacturing device for cartilage regeneration will be illustrated and described in detail.

[0162] FIG. 3 is a perspective view of a support manufacturing device for cartilage regeneration according to one embodiment of the present invention, FIG. 4 is a front view of a support manufacturing device for cartilage regeneration according to one embodiment of the present invention, FIG. 5 is a top view of a support manufacturing device for cartilage regeneration according to one embodiment of the present invention, and FIG. 6 is a cross-sectional view taken along A1-A2 of FIG. 5.

[0163] Referring to FIGS. 3 to 6, the support manufacturing device (10) for cartilage regeneration may include a stand (100).

[0164] The stand (100) may include a stand body (110) and a table (120).

[0165] The table (120) may be formed as a plate having a flat surface. A plurality of components may be arranged on the table (120). The flat surface may provide a stable seating surface for the components.

[0166] The stand body (110) may be equipped with a plurality of legs. The plurality of legs may be positioned at the corner areas of the table (120). The plurality of legs may be positioned with different or identical set lengths. The plurality of legs with adjusted set lengths may form a flat surface of the table (120).

[0167] Additionally, the plurality of legs can be arranged with a set length corresponding to the worker's working height. For example, the plurality of legs can be arranged at the worker's expected working height. The plurality of legs with adjustable heights can improve the worker's workability.

[0168] A support manufacturing device (10) for cartilage regeneration may include a frame unit (200). The frame unit (200) may be placed on a table (120). The frame unit (200) may include a frame support (220) and a frame body (210).

[0169] The frame support (220) can support the frame body (210). The frame support (220) can be placed on the upper surface of the table (120). The frame support (220) can be installed on the table (120) to fix the frame body (210). The frame support (220) and the table (120) can be fixed through a joint structure such as a fixing screw, but the fixing means is not limited to the fixing screw. In addition, the frame support (220) and the frame body (210) can also be fixed by a similar fixing means.

[0170] The frame body (210) may be placed on the table (120). For example, the frame body (210) may be positioned on the upper surface of the table (120) and supported by a frame support (220). The frame body (210) may be placed in a plate shape. Accordingly, the frame body (210) may be placed in a direction parallel to the flat surface of the table (120).

[0171] The frame body (210) may have a plurality of through holes (212, 215). The frame body (210) may have cylinder guides (213, 216) respectively arranged on the plurality of through holes (212, 215).

[0172] The plurality of through holes (212, 215) may include a first through hole (212) and a second through hole (215). A guide rod (440) may be placed in the first through hole (212). A pressure rod (420) may be placed in the second through hole (215).

[0173] A plurality of first through holes (212) may be arranged around the second through hole (215). The first through holes (212) may be arranged symmetrically around the second through hole (215).

[0174] In this embodiment, the first through-holes (212) are arranged symmetrically two around the second through-hole (215). However, the arrangement of the first through-holes (212) is not limited to this, and three to eight first through-holes (212) may be arranged symmetrically around the second through-hole (215).

[0175] The guide rod (440) can distribute the concentrated pressure provided from the pressure rod (420) in the surface direction of the pressure plate (430). Therefore, the number of first through holes (212) arranged is related to the number of guide rods (440) arranged, and thus can play a role in forming a distributed pressure of the pressure plate (430). The pressure plate (430) formed with a distributed pressure can help form a uniform surface pressure in the forming unit (500).

[0176] The support manufacturing device for cartilage regeneration (10) may include a transport unit (300).

[0177] Here, for easy explanation, in the table (120), the area housed by the frame support (220) and the frame body (210) is defined as the forming area (PA), and the area other than the forming area (PA) is defined as the peripheral area (SA). Among the peripheral areas (SA), the area where the transfer unit (300) is placed is defined as the loading area (LA).

[0178] The transport unit (300) may include a transport rail (310), a carrier (320), and a transport drive unit (330).

[0179] The transport rail (310) may be arranged on the upper surface of the table (120). The transport rail (310) may be arranged from the loading area (LA) to the forming area (PA). The transport rail (310) may form a rail portion with a pair of rails arranged in the direction from the loading area (LA) to the forming area (PA). At least one rail portion may be arranged. For example, when the transport rail (310) has multiple rail portions formed in the direction from the loading area (LA) to the forming area (PA), the loading area (LA) may form multiple work windows.

[0180] A carrier (320) can be placed on a transport rail (310). The carrier (320) can move along the transport rail (310). Accordingly, the carrier (320) can be placed in a loading area (LA) and a forming area (PA).

[0181] The carrier (320) can be movably coupled to the transport rail (310). For example, the carrier (320) can be slidably coupled to the transport rail (310), but is not limited thereto. Any structure that allows for movement can be used to couple the carrier (320) and the transport rail (310).

[0182] The carrier (320) may include a sliding portion (322) having a sliding structure and a mounting surface (328) arranged on the opposite side of the sliding portion (322). The sliding portion (322) may be coupled to a transport rail (310). A lower plate (510) may be mounted on the mounting surface (328). The mounting surface (328) may face the lower plate (510).

[0183] The carrier (320) can be connected to a transport drive unit (330). The transport drive unit (330) can be connected to a thickness surface formed between the sliding unit (322) and the seating surface (328).

[0184] The transport drive unit (330) may be positioned in the peripheral area (SA). The transport drive unit (330) may be configured with an actuator to move the carrier (320) to the loading area (LA) and the forming area (PA). In the present embodiment, a structure in which the actuator moves forward and backward is illustrated and described, but in some cases, the carrier (320) may be moved through a structure in which the actuator moves left and right.

[0185] A support manufacturing device (10) for cartilage regeneration may include a pressurizing unit (400). The pressurizing unit (400) may be placed on a molding area (PA). The pressurizing unit (400) may include a pressurizing unit body (410), a pressurizing rod (420), a pressurizing plate (430), and a guide rod (440).

[0186] The pressurizing unit body (410) may be placed on the upper surface of the frame body (210). The pressurizing unit body (410) may include an actuator. The actuator may move the pressurizing rod (420) in the up and down direction.

[0187] The pressurizing rod (420) can be placed in a second through hole (215) that penetrates the upper and lower surfaces of the frame body (210). For example, the pressurizing rod (420) can be fitted into a second cylinder guide (216) placed in the second through hole (215).

[0188] The pressure rod (420) can move up and down. The pressure rod (420) can move to contact the pressure plate (430). The pressure rod (420) can move the pressure plate (430) downward. The pressure rod (420) can apply pressure to the pressure plate (430) when it faces the molding object in the target area.

[0189] The pressurizing unit (400) may include a pressurizing plate (430) placed between the frame body (210) and the table (120).

[0190] The pressure plate (430) may include a pressure plate upper surface (437) with which the pressure rod (420) comes into contact. A mounting portion (439) may be provided on the pressure plate upper surface (437). The pressure rod (420) may be mounted on the mounting portion (439).

[0191] The mounting portion (439) may be positioned in an area including the center of gravity of the pressure plate (430). For example, if the pressure plate (430) is positioned in a square shape, the center of gravity of the pressure plate (430) may be the center area of ​​the square shape. Accordingly, the mounting portion (439) may be positioned on the center area.

[0192] One end of the pressure rod (420) can be mounted on the mounting portion (439). The mounting portion (439) can be formed of a material capable of withstanding the pressure force, such as rubber or silicone, on the upper surface (438) of the pressure plate.

[0193] In this way, the pressure rod (420) can move downward and the pressure rod (420) can move the pressure plate (430) downward. And, when the pressure plate (430) moves to the target location, the pressure rod (420) can provide a pressure force to the center of gravity of the pressure plate (430).

[0194] A guide rod (440) may be placed around the pressure rod (420). The guide rod (440) may be placed between the frame body (210) and the pressure plate (430).

[0195] One end of the guide rod (440) can be coupled to the pressure plate (430). The other end of the guide rod (440) can be inserted into a first through hole (212) that penetrates a portion of the frame body (210). For example, a first cylinder guide (213) can be placed in the first through hole (212) formed in the frame body (210). The guide rod (440) can be fitted into the first cylinder guide (213).

[0196] As described above, a plurality of first through holes (212) may be symmetrically arranged around the second through hole (215). A guide rod (440) may be arranged in each of the plurality of first through holes (212).

[0197] Accordingly, a plurality of guide rods (440) can be symmetrically arranged around the pressure rod (420). The plurality of guide rods (440) can serve to distribute the pressure so that the forming unit (500) can form a uniform surface pressure. The plurality of guide rods (440) can form a uniform pressure on the entire surface of the pressure plate (430).

[0198] Meanwhile, a gimbal member (450) may be placed between the guide rod (440) and the pressure plate (430). For example, the gimbal member (450) may connect the lower surface of the guide rod (440) and the upper surface of the pressure plate (430). In addition, the gimbal member (450) may also be selectively placed between the mounting member (439) and the pressure plate (430). The gimbal member (450) may connect the lower surface of the mounting member (439) and the upper surface of the pressure plate (430).

[0199] The gimbal unit (450) can be symmetrically arranged around the mounting unit (439) with the mounting unit (439) as the center. In other words, as a plurality of guide rods (440) are arranged around an area including the center of gravity of the pressing plate (430) on the upper surface of the pressing plate (430), the gimbal unit (450) arranged on each of the plurality of guide rods (440) can also be arranged in the same arrangement structure.

[0200] The gimbal unit (450) can adjust the inclination of the pressure plate (430). For example, the gimbal unit (450) can adjust the horizontality of the upper plate (520). That is, the gimbal unit (450) can rotate (adjust the inclination) of the upper plate (520).

[0201] If the inclination of the upper plate (520) is not horizontal, the gimbal unit (450) can rotate the upper plate (520) to level the upper plate (520).

[0202] Accordingly, the gimbal unit (450) rotates (tilts) the upper plate (520) to level it, so that the load of the upper plate (520) can be provided to the second mold (1200 of FIG. 18). For example, since the upper plate (520) is coupled to the pressure plate (430), the loads of the upper plate (520) and the pressure plate (430) can be provided to the second mold (1200).

[0203] The gimbal unit (450) can adjust pressure imbalances that may occur due to differences in the thickness of the molding object. For example, when the thicknesses of the molding objects are different, the gimbal unit (450) can adjust the inclination of the pressure plate (430) so that the pressure plate (430) corresponds to the whole surface of one surface of the molding object.

[0204] Accordingly, when the thickness of some areas of the molding object is different from that of other areas, the gimbal unit (450) can prevent the pressure plate (430) from concentrating the pressure force on some areas of the molding object or transmitting more pressure force to them.

[0205] In this way, the gimbal unit (450) can improve the molding uniformity of the molding target by adjusting the inclination of the pressure plate (430).

[0206] A support manufacturing device (10) for cartilage regeneration may include a molding unit (500). The molding unit (500) may include a lower plate (510), an upper plate (520), and a pressure distribution unit (550).

[0207] The lower plate (510) may be placed on the upper surface of the carrier (320). For example, the lower plate (510) may be mounted on the mounting surface (328) of the carrier (320). The lower plate (510) may be formed in a shape similar to or smaller than the shape of the carrier (320).

[0208] The lower surface (512) of the lower plate (510) can be mounted on the mounting surface (328) of the carrier (320). The carrier (320) can move between the loading area (LA) and the forming area (PA) along the transport rail (310). Accordingly, the lower plate (510) mounted on the carrier (320) can move between the loading area (LA) and the forming area (PA) via the carrier (320).

[0209] The lower plate (510) may include an upper surface (517) of the lower plate (510) on the opposite side of the lower surface (512) of the lower plate (510). A lower mold (800 of FIG. 18) may be placed on the upper surface (517) of the lower plate (510). The manufacturing method with respect to the lower mold (800) will be described in detail.

[0210] The upper plate (520) may be placed in the forming area (PA). The upper plate (520) may be coupled to the pressure plate (430). The upper plate (520) may include an upper plate coupling surface (527) coupled to the pressure plate (430). For example, the upper plate coupling surface (527) may be coupled to a lower surface (432) of the pressure plate (430). The lower surface (432) of the pressure plate may be a surface facing the upper surface (437) of the pressure plate on which the mounting portion (439) is arranged.

[0211] The shape of the upper plate (520) may be formed to have a larger area than the shape of the lower plate (510). A molding object may be placed between the upper plate (520) and the lower plate (510). Since the upper plate (520) has a larger area than the shape of the lower plate (510), it can provide uniform pressure to the molding object. Therefore, the size of the molding object may be limited by the shape of the lower plate (510).

[0212] As described above, the cartilage regeneration support manufacturing device (10) according to the present invention can form a press plate (430) in which a uniform press force is formed by dispersing the press force, thereby increasing the area of ​​the lower plate (510). Accordingly, a molding object placed on the lower plate (510) can be formed over a large area.

[0213] The upper plate (520) may include an upper plate pressure surface (522) on the opposite side of the upper plate joining surface (527). A pressure distribution unit (550) may be arranged on the upper plate pressure surface (522).

[0214] The pressure distribution unit (550) can be bonded to the upper plate pressure surface (522) using an adhesive. The pressure distribution unit (550) can be formed of a silicone material, but is not limited thereto, and any material capable of transmitting pressure can be used. The pressure distribution unit (550) can evenly distribute the pressure input from the pressure plate (430) across the entire surface of the upper plate (520).

[0215] A support manufacturing device (10) for cartilage regeneration may include an input unit (600) and a display unit (700). The input unit (600) and the display unit (700) may be placed in a peripheral area (SA).

[0216] The support manufacturing device (10) for cartilage regeneration may include an input unit (600) that receives input from a worker. For example, the input unit (600) allows the worker to directly input a set value.

[0217] The input unit (600) may include input means such as an input button for inputting a setting value. Here, the setting value may include, for example, the pressure of the pressurizing unit (400), the heating temperature of the lower plate (510), the pressure provision time and heating time of the pressurizing unit (400), etc.

[0218] The display unit (700) can display the above-mentioned setting values ​​on the screen. In other words, the display unit (700) can display input information on the screen. For example, the display unit (700) can display the pressure of the pressurizing unit (400), the heating temperature of the lower plate (510), the pressure application time, the heating time, etc. in numerical values.

[0219] In addition, a control unit capable of controlling the setting values ​​of the support manufacturing device (10) for cartilage regeneration may be further placed in the space where the display unit (700) is placed.

[0220] In this way, the cartilage regeneration support manufacturing device (10) according to the embodiment of the present invention forms a uniform pressure, so that a cartilage regeneration support with improved uniformity can be manufactured.

[0221] Figure 7 is a block diagram illustrating a device for manufacturing a support for cartilage regeneration according to an embodiment of the present invention.

[0222] To avoid redundant explanation and for easy explanation, Fig. 7 will be described by citing Figs. 3 to 6.

[0223] The support manufacturing device (10) for cartilage regeneration according to an embodiment of the present invention may include a sensor unit (30) and a control unit (50).

[0224] The control unit (50) can be connected to the display unit (700), the input unit (600), and the sensor unit (30). The control unit (50) can be placed in the area where the display unit (700) is placed.

[0225] The control unit (50) may also be connected to a configuration in which the sensor unit (30) is arranged. For example, the control unit (50) may be connected to a configuration in which a pressure sensor (470) and / or a temperature sensor (515) are arranged.

[0226] For example, if a temperature sensor (515) is disposed on the lower plate (510), the control unit (50) may be connected to the lower plate (510). For another example, if a pressure sensor (470) is disposed on the pressurizing unit (400), the control unit (50) may be connected to the pressurizing unit (400). The sensor unit (30) may include a pressure sensor (470). The pressure sensor (470) may be disposed on the upper surface of the frame body (210).

[0227] In this drawing, a drawing in which a pressure sensor (470) is placed in a pressurizing unit (400) is illustrated and explained. Here, the pressure sensor (470) may also be placed in a forming unit (500).

[0228] The input unit (600) can receive input from the operator. The input unit (600) can input a pressure to be provided to the pressurizing rod (420) of the pressurizing unit (400). The input provided may be a set pressure at which the pressurizing unit (400) operates. The input unit (600) can form a first signal (SG1) composed of the set pressure.

[0229] The input unit (600) can provide a first signal (SG1) to the control unit (50). The control unit (50) can convert the provided first signal (SG1) and transmit it to the display unit (700) and the pressurizing unit (400).

[0230] The control unit (50) can convert the first signal (SG1) and transmit the first-first signal (SG11) to the display unit (700). The display unit (700) that receives the first-first signal (SG11) can display the set pressure on the screen.

[0231] Additionally, the control unit (50) can convert the first signal (SG1) and transmit the first-second signal (SG1)2) to the pressurizing unit (400).

[0232] The pressurizing unit (400) can operate according to the first-second signal (SG12). For example, the pressurizing unit (400) can operate the pressurizing rod (420) according to the first-second signal (SG12). For example, the pressurizing rod (420) can move the pressurizing plate (430) according to the first-second signal (SG12). When the pressurizing plate (430) moves according to the first-second signal (SG12) and comes into contact with the molding object, the pressurizing rod (420) can provide pressure to the pressurizing plate (430).

[0233] The pressure sensor (470) of the sensor unit (30) can sense the pressure formed in the pressurizing unit (400). The sensor unit (30) can form a second signal (SG2) with information obtained by sensing the pressure formed in the pressurizing unit (400). The sensor unit (30) can transmit the second signal (SG2) to the control unit (50).

[0234] The control unit (50) that receives the second signal (SG2) can calculate whether information according to the first-second signal (SG12) is transmitted as pressure through the pressurization unit (400). For example, the control unit (50) can calculate the difference between the pressure set in the pressurization rod (420) and the pressure transmitted from the pressure sensor (470). The control unit (50) can form the third signal (SG3) and the fourth signal (SG4) from the value obtained by calculating the difference in pressure (hereinafter, “calculated value”).

[0235] If the above operation value is within the error range compared to the measured data, the control unit (50) can transmit the fourth signal (SG4) to the display unit (700). In addition, the control unit (50) can generate a third signal (SG3) that is identical to the first-second signal (SG12) and provide the third signal (SG3) to the pressurizing unit (400).

[0236] Meanwhile, if the above operation value is outside the error range compared to the measured data, the control unit (50) can provide a corrected input value to the pressurization unit (400).

[0237] Here, when the control unit (50) is set manually, a fourth signal (SG4) composed of the above operation values ​​can be transmitted to the display unit (700). The display unit (700) can display the operation values ​​according to the fourth signal (SG4) on the screen.

[0238] The operator can check the above calculation value displayed on the display unit (700). The operator can input the corrected input value based on the displayed information into the input unit (600).

[0239] The control unit (50) can generate a third signal (SG3) using the corrected input value. The third signal (SG3) formed by the control unit (50) can be transmitted to the pressurizing unit (400). Through the third signal (SG3), the pressurizing unit (400) can provide the corrected pressure value to the pressurizing plate (430). The corrected pressure value can be the pressure provided to the pressurizing plate (430).

[0240] Additionally, the control unit (50) can generate a 4-1 signal (SG4-1) based on information according to the 3rd signal (SG3). The 4-1 signal (SG4-1) can be provided to the display unit (700). The display unit (700) can display information composed of the 4-1 signal (SG4-1) on the screen.

[0241] In this way, the support manufacturing device (10) for cartilage regeneration according to the present invention can control the pressure provided to the pressurizing unit (400) through the sensor unit (30).

[0242] Meanwhile, if the control unit (50) is set to automatic and the value calculated from the difference in pressure (hereinafter referred to as “calculated value”) shows a difference, the fourth signal (SG4) may not be generated.

[0243] The pressure sensor (470) can sense the pressure formed in the pressurization unit (400). Through the sensing information, the sensor unit (30) can generate a second-first signal (SG21). The sensor unit (30) can transmit the second-first signal (SG21) to the control unit (50).

[0244] The control unit (50) can determine whether the calculated value is within the error range by comparing it with the measured data based on the measured data. If it is determined that the calculated value is within the error range, the control unit (50) can generate a third signal (SG3) that is identical to the first-second signal (SG12).

[0245] The third signal (SG3) formed in the control unit (50) can be transmitted to the pressurizing unit (400). Through the third signal (SG3), the pressurizing unit (400) can provide pressure according to the first-second signal (SG12) to the pressurizing plate (430). The pressure according to the first-second signal (SG12) can be the pressure provided to the pressurizing plate (430).

[0246] Additionally, the control unit (50) can generate a fourth signal (SG4) based on information according to the third signal (SG3). The fourth signal (SG4) can be provided to the display unit (700). The display unit (700) can display information composed of the fourth signal (SG4) on the screen.

[0247] In this way, the support manufacturing device (10) for cartilage regeneration according to the present invention can control the pressure provided to the pressurizing unit (400) through the sensor unit (30).

[0248] Alternatively, the control unit (50) may compare the input pressure with the pressure provided to the molding object. For example, the pressurizing unit (400) may provide pressure to the molding unit (500). For example, the pressurizing unit (400) may transmit the pressure formed on the pressurizing plate (430) to the molding unit (500).

[0249] A difference may occur between the pressure formed in the pressurizing unit (400) and the pressure formed in the forming unit (500). The control unit (50) may compare the pressure provided by the pressurizing unit (400) with the pressure output from the forming unit (500). The output pressure may be the pressure provided to the forming object.

[0250] The above-mentioned pressure can be provided to the forming unit (500) through the pressure plate (430). The above-mentioned output pressure provided to the forming object can be formed through the forming unit (500).

[0251] The pressure sensor (470) of the sensor unit (30) can be placed in each of the pressurizing unit (400) and the forming unit (500). The pressure sensor (470) can sense the supply pressure of the pressurizing unit (400). In addition, the pressure sensor (470) can sense the output pressure of the forming unit (500).

[0252] The sensor unit (30) can generate a second signal composed of the above-mentioned provided pressure and the above-mentioned output pressure.

[0253] There may be a difference (hereinafter referred to as "pressure difference") between the input pressure from the pressurizing rod (420) and the output pressure from the forming unit (500). For example, a pressure difference may occur during the process of distributing pressure on the front surface of the pressurizing plate (430) or during the process of distributing pressure in the pressure distributing unit (550).

[0254] In such cases, the probability of molding defects in molded products may increase. Furthermore, power loss from the manufacturing equipment may occur.

[0255] The pressure sensor (470) senses the pressure in each set zone, and the sensor unit (30) can convert the pressure in each set zone into a signal and transmit the second signal (SG2) to the control unit (50).

[0256] The control unit (50) can calculate the pressure difference. Reflecting the calculated value, the setting value of the pressurization unit (400) can be readjusted. Furthermore, the coupling structure between components can be readjusted. Accordingly, the pressure sensor (470) can reduce the probability of defects and reduce power loss resulting from leakage of the manufacturing device.

[0257] FIG. 8 is a plan view illustrating a shape of a press plate of a press unit according to an embodiment of the present invention, FIG. 9 is a plan view illustrating another shape of a press plate of a press unit according to an embodiment of the present invention, and FIG. 10 is a plan view illustrating another shape of a press plate of a press unit according to an embodiment of the present invention.

[0258] To avoid redundant explanation, FIGS. 8 to 10 will be described by citing FIGS. 3 to 6 for easy explanation.

[0259] Referring to FIGS. 8 to 10, the pressurizing unit (400) may include a pressurizing rod (420), a pressurizing plate (430), and a guide rod (440).

[0260] The pressure plate (430) may include a mounting portion (439). The mounting portion (439) may be positioned in an area including the center of gravity of the pressure plate (430). A pressure rod (420) may be positioned at a position corresponding to the mounting portion (439).

[0261] A guide rod (440) may be arranged around the pressure rod (420). The guide rod (440) may be arranged symmetrically around the pressure rod (420). The symmetrically arranged guide rods (440) may form a pressure force distributed on the entire surface of the pressure plate (430).

[0262] Meanwhile, the lower plate (510) of the forming unit (500) may be arranged in a shape with a smaller area than the upper plate (520). And the upper plate (520) may be combined with the pressure plate (430) in the same shape.

[0263] Accordingly, the pressure provided from the pressure plate (430) in which the distributed pressure is formed can be transmitted to the upper plate (520). The upper plate (520) that has received the pressure can pressurize the molding object by facing the lower plate (510).

[0264] Therefore, the pressure plate (430) in which the pressure force distributed over the whole surface is formed can help form a uniform surface pressure on the forming unit (500).

[0265] In FIGS. 3 to 6, the shape of the pressure plate (430) is formed in a rectangular shape, and the guide rods (440) can be arranged symmetrically on both sides of the pressure rod (420) with the pressure rod (420) as the center. Accordingly, two guide rods (440) can be arranged so that they are connected to the pressure plate (430).

[0266] Referring to Fig. 8, the pressure plate (430) has an identical rectangular shape, and the guide rod (440) can be arranged symmetrically at the corner area of ​​the pressure plate (430) with the pressure rod (420) as the center. Accordingly, four guide rods (440) can be arranged so that they are connected to the pressure plate (430).

[0267] In this way, by symmetrically arranging four guide rods (440) on the pressure plate (430) around the pressure rod (420), the distribution of the pressure force can be further improved.

[0268] Referring to Fig. 9, the pressure plate (430) may be formed in a triangular shape. Three guide rods (440) may be arranged on the triangular pressure plate (430). For example, when the pressure plate (430) is triangular in shape, three guide rods (440) may be arranged on the pressure plate (430) so that the guide rods (440) are arranged symmetrically around the pressure rod (420).

[0269] In this way, when the pressure plate (430) has a triangular shape, the pressure distribution can be further improved by arranging three guide rods (440) symmetrically around the pressure rod (420) on the pressure plate (430).

[0270] Referring to Fig. 10, the pressure plate (430) may be formed in a circular shape. Four to eight guide rods (440) may be arranged on the circular pressure plate (430). In the present embodiment, a case in which eight guide rods (440) are arranged on the pressure plate (430) is illustrated.

[0271] Specifically, when the pressure plate (430) has a circular shape, 4 to 8 guide rods (440) can be placed on the pressure plate (430) so that the guide rods (440) are symmetrically placed around the pressure rod (420).

[0272] In this way, when the pressure plate (430) has a circular shape, the pressure distribution can be further improved by arranging 4 to 8 guide rods (440) symmetrically around the pressure rod (420) on the pressure plate (430).

[0273] FIG. 11 is a flowchart illustrating a method for manufacturing a support for cartilage regeneration using a support manufacturing device for cartilage regeneration according to an embodiment of the present invention, FIGS. 12 to 14 are flowcharts illustrating detailed methods for manufacturing a support for cartilage regeneration according to each step of FIG. 11, and FIGS. 15 to 20 are process diagrams illustrating a method for manufacturing a support for cartilage regeneration using a support manufacturing device for cartilage regeneration according to an embodiment of the present invention.

[0274] To avoid redundant explanation and for easy explanation, FIGS. 11 to 20 will be described by citing FIGS. 3 to 6.

[0275] The method for manufacturing a support for cartilage regeneration according to an embodiment of the present invention can form a support for cartilage regeneration using a cartilage regeneration support manufacturing device (10).

[0276] A cartilage regeneration support manufacturing device (10) may include a transport unit (300), a forming unit (500), and a pressurizing unit (400). The forming unit (500) may include an upper plate (520) and a lower plate (520). A forming object may be placed between the upper plate (520) and the lower plate (510). The cartilage regeneration support manufacturing device (10) may provide pressure to the forming object to form a cartilage regeneration support with improved pattern uniformity on one or both sides.

[0277] Hereinafter, the present invention will be described in more detail through examples.

[0278]

[0279] Example

[0280] Example 1. Manufacturing of large-area PLGA sheets (cross-sectional patterns) and uniformity measurement

[0281] A support for cartilage regeneration was manufactured using the manufacturing device of Fig. 3.

[0282] As shown in Fig. 1, a cross-sectional PDMS mold (flat) was placed on a plate, and 12 ml of a PLGA solution (containing 10 ml of chloroform and 2.5 g of PLGA) in which 25 g of PLGA was dissolved in 100 ml of chloroform) was evenly applied to a 12*12 cm size on the PUA mold (800 nm). Afterwards, the PLGA solution was turned over so that it was facing down and placed on the PDMS mold. Pressure was applied using the manufacturing device of Fig. 3 to perform pattern forming at room temperature for 40 minutes.

[0283] After pattern forming, the solution was placed on a 70°C hot plate with the solution facing upward and the solvent was evaporated (approximately 1 hour). The hardened PLGA sheet was carefully separated from the PUA mold. The separated PLGA large-area scaffold was immersed in 70% ethanol for approximately 10 seconds and then washed with purified water. The washed scaffold was dried for more than 8 hours and then cut to the appropriate size. The above process was repeated four more times to produce a total of five large-area PLGA sheets (Fig. 21).

[0284] The thickness of five points of the prepared large-area PLGA sheets was randomly measured, and the average value for each sample and the overall average value of the measurement data were recorded (Fig. 22).

[0285]

[0286] Example 2. Fabrication of large-area PLGA sheets (double-sided patterns)

[0287] A support for cartilage regeneration was manufactured using the manufacturing device of Fig. 3.

[0288] As shown in Fig. 1, a double-sided PDMS mold (800 nm) was placed on a plate, and 12 ml of a PLGA solution (containing 10 ml of chloroform and 2.5 g of PLGA) in which 25 g of PLGA was dissolved in 100 ml of chloroform) was evenly applied to a 12*12 cm size on the PUA mold (800 nm). After that, the PLGA solution was turned over so that it was facing down and placed on the PDMS mold. After applying pressure using the manufacturing device of Fig. 3 and setting the temperature to 50°C, pattern forming was continued for 60 minutes.

[0289] After pattern forming, the upper and lower molds were not separated and placed on a 70℃ hot plate. Then, the molds were pressed with a steel plate weighing about 1.2 kg to prevent separation and dried for more than 5 hours. The hardened PLGA was carefully separated from the PDMS and PUA molds. The separated PLGA large-area scaffold was immersed in 70% ethanol for about 10 seconds and then washed three times with purified water. The washed scaffold was dried with a blower for about 30 minutes and then cut to a size suitable for the dimensions. The above process was repeated four more times to produce a total of five large-area PLGA sheets.

[0290]

[0291] Example 3. Measurement of the pattern between the valleys and peaks of a large-area PLGA sheet using FE-SEM imaging.

[0292] The distance between the valleys and peaks of the nano-patterns and the uniformity of the pattern were measured through FE-SEM photography of the sheets of Examples 1 and 2 under the following conditions.

[0293] - Resolution: 0.6nm

[0294] - Magnification: X20~ 2,000,000

[0295] - EDS detector (ATW2, 127eV, 50mm 2 )

[0296] As a result, the distance between each pattern and the peak of the large-area sheets of Examples 1 and 2 was 790 nm, respectively, and the peaks and valleys maintained a ratio of 1:1 (Fig. 23). In addition, the deviation between five arbitrary points of the peaks of the nano-patterns and five arbitrary points of the valleys was substantially less than 10 nm, which was practically nonexistent.

Claims

1. Made of biocompatible polymers; A pattern for cartilage regeneration is formed on one side or both sides. The above pattern consists of repeating peaks and valleys, The above pattern is a support for cartilage regeneration, in which an area satisfying the uniformity (U) of the following mathematical formula 1 is 95% or more of the total area: [Mathematical Formula 1] U = |H P1 - H P2 |≤ 0.1H n (In the above formula, H P1 is the height at P1, H P2 refers to the height at P2 and H n refers to the height difference between the peak and valley of the normal pattern).

2. A support for cartilage regeneration according to claim 1, wherein both P1 and P2 are points located on the floor or both are points located on the bone.

3. A support for cartilage regeneration according to claim 1, wherein the area satisfying the uniformity of the mathematical expression 1 is 99% or more of the total area.

4. A support for cartilage regeneration having a thickness of 30 to 100 ㎛ according to claim 1.

5. A support for cartilage regeneration according to claim 1, wherein the biocompatible polymer is any one selected from the group consisting of polycaprolactone, polylactide-co-glycolide, polyethylene glycol, polyethylene oxide, polylactic acid, and polyglycolic acid.

6. A support for cartilage regeneration according to claim 1, wherein the biocompatible polymer is polylactide-co-glycolide containing 65 to 85 mol% of lactide and 15 to 35 mol% of glycolide.

7. A support for cartilage regeneration according to claim 1, wherein the pattern is a straight or curved shape in which the peaks and valleys are repeated in parallel.

8. A support for cartilage regeneration according to claim 1, wherein any one selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs is applied to the cross-section or both surfaces.

9. A support for cartilage regeneration according to claim 1, wherein fibrin is applied to the edge.

10. A step of manufacturing a sheet-shaped semi-hardened article by applying a polymer solution containing a biocompatible polymer onto a polyurethane acrylate mold; A step of manufacturing a patterned semi-hardened article by applying pressure to the semi-hardened article with a polydimethylsiloxane mold; and A method for producing a support for cartilage regeneration according to any one of claims 1 to 9, comprising the step of drying the patterned semi-hardened material.

11. A method for producing a support for cartilage regeneration according to claim 10, wherein the patterned semi-hardened material is produced by positioning the semi-hardened material between the polyurethane acrylate mold and the polydimethylsiloxane mold and then applying pressure with upper and lower plates.

12. A method for manufacturing a support for cartilage regeneration according to claim 10, wherein the polyurethane acrylate mold or the polydimethylsiloxane mold has unevenness formed for forming the pattern.

13. A method for manufacturing a support for cartilage regeneration according to claim 11, wherein the upper plate has a pressure rod and a guide rod.

14. A method for producing a support for cartilage regeneration according to claim 10, wherein the pressure is 0.40 Pa to 0.70 Pa.

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