Cartilage regeneration scaffold and production method for the same

Abstract

To provide: a cartilage regeneration scaffold excellent in thickness uniformity and pattern uniformity, and also excellent in a cartilage regeneration effect and adhesion to an affected site; and a production method for the same.SOLUTION: The invention relates to a cartilage regeneration scaffold and a production method for the same, and more specifically, a cartilage regeneration scaffold and a production method for the same where the cartilage regeneration scaffold is produced by a scaffold manufacturing apparatus including predetermined molds and structures, so that, even when produced in a large area, uniformity in the thickness of a biocompatible polymer sheet and uniformity of a pattern formed on the sheet are excellent, resulting in an excellent cartilage regeneration effect and adhesion to an affected site.SELECTED DRAWING: Figure 1

Description

Technical Field

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

Background Art

[0002] Cartilage is a bone tissue composed of chondrocytes and a cartilage matrix that surrounds them. Chondrocytes function to synthesize and secrete the cartilage matrix inside the cartilage. The cartilage matrix functions to give elasticity to the cartilage. Different from other tissues, cartilage has no blood vessels or nerves distributed, so once damaged, it is difficult to regenerate. Since the self-repair ability of cartilage is insufficient in this way, surgical treatments such as microfracture surgery are required to treat damaged cartilage.

[0003] Microfracture surgery is a surgical method aimed at regenerating damaged cartilage. It creates fine fractures in the bone where the cartilage is damaged and exposed. When the subchondral bone is damaged, bone marrow components including bone marrow stem cells leak out, and these cells differentiate to form cartilage. It is a technology that utilizes this principle.

[0004] Most of the cartilage generated by microfracture surgery is fibrous cartilage rather than hyaline cartilage. Since fibrous cartilage is rich in type I collagen and has a low proteoglycan content, its ability to withstand wear is low. Therefore, when the damaged cartilage tissue regenerates into fibrous cartilage, symptoms improve by 60 - 70% until about 2 years after the surgery, but then structural destruction occurs and the symptoms may worsen. Also, it is known that the larger the defect site, the more severe the symptoms become. Microfracture surgery treatment has limitations in treating extensive cartilage defects and has the drawback that fibrous cartilage with weak mechanical properties regenerates. Therefore, in combination with microfracture surgery treatment, it is necessary to transplant a support for cartilage regeneration to the cartilage defect site to promote cartilage regeneration and improve the maturity during the cartilage regeneration process.

[0005] The support for cartilage regeneration must have a uniform thickness and pattern so that chondrocytes can grow densely and uniformly. However, with conventional methods, there are limitations in making the thickness and pattern of the support for cartilage regeneration uniform. In particular, when manufacturing a support for cartilage regeneration with an area of a certain size or more, the non-uniformity of the thickness and pattern increases significantly.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object 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] An object of the present invention is to provide a support for cartilage regeneration that can adhere to a cartilage defect site with high adhesion, and a method for manufacturing the same.

Means for Solving the Problems

[0009] 1. A support for cartilage regeneration made of a biocompatible polymer, having a pattern for cartilage regeneration formed on one or both sides, the pattern consisting of repeated peaks and valleys, and the area satisfying the uniformity (U) of the following Mathematical Formula 1 being 95% or more of the total area. [Mathematical Formula 1] U = |H P1 - H P2 | ≤ 0.1H n (In the formula, H P1 is the height at P1, H P2 is the height at P2, and H n means the difference in height between the peak and the valley of the normal pattern.) 2. In the above item 1, the cartilage regeneration support, wherein P1 and P2 are both points located at peaks or both at valleys.

[0010] 3. In the above item 1, the cartilage regeneration support, wherein the area satisfying the uniformity of Mathematical Formula 1 is 99% or more of the total area.

[0011] 4. In the above item 1, the cartilage regeneration support, wherein the thickness is 30 to 100 μm.

[0012] 5. In the above item 1, the cartilage regeneration support, 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.

[0013] 6. In the above item 1, the cartilage regeneration support, wherein the biocompatible polymer is polylactide-co-glycolide of 65 to 85 mol% of lactide and 15 to 35 mol% of glycolide.

[0014] 7. In the above item 1, the cartilage regeneration support, wherein the pattern is linear or curved with peaks and valleys arranged and repeated.

[0015] 8. In the above item 1, the cartilage regeneration support, wherein any one selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs is coated on one or both sides.

[0016] 9. In the above item 1, the cartilage regeneration support, wherein fibrin is coated on the edge.

[0017] 10. A method for manufacturing the cartilage regeneration support according to any one of the above items 1 to 9, comprising the steps of coating a polymer solution containing a biocompatible polymer on a polyurethane acrylate mold to produce a sheet-like semi-cured product, applying pressure to the semi-cured product with a polydimethylsiloxane mold to produce a patterned semi-cured product, and drying the patterned semi-cured product.

[0018] 11. In the item 10 above, the method for manufacturing a cartilage regeneration support, wherein the patterned semi-cured material is manufactured by placing the semi-cured material between a polyurethane acrylate mold and a polydimethylsiloxane mold and then applying pressure with upper and lower plates.

[0019] 12. In the item 10 above, the method for manufacturing a cartilage regeneration support, wherein the polyurethane acrylate mold or the polydimethylsiloxane mold has unevenness formed thereon for pattern formation.

[0020] 13. In the item 11 above, the method for manufacturing a cartilage regeneration support, wherein the upper plate includes a pressure rod and a guide rod.

[0021] 14. In the item 10 above, the method for manufacturing a cartilage regeneration support, wherein the pressure is 0.40 Pa to 0.70 Pa.

Advantages of the Invention

[0022] The cartilage regeneration support of the present invention is excellent in cartilage regeneration effect.

[0023] The cartilage regeneration support of the present invention is excellent in adhesion.

[0024] The cartilage regeneration support of the present invention is excellent in workability.

Brief Description of the Drawings

[0025]

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Mode for Carrying Out the Invention

[0026] The present invention provides a cartilage regeneration support and a method for manufacturing the same.

[0027] The present invention provides a cartilage regeneration support and a method for manufacturing the same, which are manufactured by a manufacturing apparatus for a support including a predetermined mold and structure, and even when manufactured in a large area, are excellent in the uniformity of the thickness of a biocompatible polymer sheet and the uniformity of the pattern formed on the sheet, and are excellent in the cartilage regeneration effect and the adhesion to the affected part.

[0028] The present invention provides a cartilage regeneration support made of a biocompatible polymer, having a pattern for the growth of cartilage cells formed on one or both sides, the pattern consisting of repeated peaks and valleys, and the area satisfying the uniformity (U) of the following Mathematical Formula 1 being 95% or more of the total area.

[0029] [Mathematical Formula 1] U = |H P1 - H P2 | ≦ 0.1H n (In the above formula, H P1 is the height at P1, H P2 is the height at P2, H n means the difference in height between the peak and the valley of a normal pattern.) Despite its thin thickness, the cartilage regeneration support of the present invention has a high degree of uniformity and appropriate elongation rate and tensile strength as a cartilage regeneration support, so it has excellent cartilage regeneration effect and excellent adhesion to the affected area.

[0030] The cartilage regeneration support of the present invention is made of a biocompatible polymer.

[0031] The biocompatible polymer is not limited to those made of specific materials. For example, it may be any one selected from the group consisting of polylactide-co-glycolide (PLGA), polycaprolactone (PCL), polyethylene glycol (PEG), polyethylene oxide (PEO), poly lactic acid (PLA), and polyglycolic acid (PGA).

[0032] From the viewpoints of uniformity and physical properties (such as elongation rate and tensile strength), the cartilage regeneration support is preferably made of polylactide-co-glycolide or polycaprolactone. In order to achieve the object of the present invention, it is more preferably made of PLGA containing Lactide (LA) monomer and Glycolide (GA) monomer in a molar ratio of 65 to 85:35 to 15.

[0033] The biocompatible polymer of the present invention has a pattern for the growth of chondrocytes formed on one or both sides.

[0034] When the cartilage regeneration support is attached to the affected area, chondrocytes existing around the support grow along the valleys of the pattern, inducing the regeneration of damaged cartilage.

[0035] The pattern may be formed on one side or both sides. In order to easily distinguish the upper and lower surfaces of the cartilage regeneration support, the pattern can be formed only on the upper surface or the lower surface. Also, when the size of the cartilage regeneration support is small, patterns may be formed on both sides so that there is no distinction between the upper and lower surfaces.

[0036] The pattern is not limited to a specific shape as long as it is a shape in which mountains and valleys are repeated. The pattern may be, for example, linear or curved in which mountains and valleys are arranged and repeated. The shape of the pattern may be a straight line parallel to any one edge of the cartilage regeneration support, a diagonal line forming a predetermined angle with any one corner, a wavy curve, or the like.

[0037] A mountain refers to a relatively protruding part, and a valley refers to a relatively recessed part existing between mountains. Cartilage cells grow along the valleys between mountains.

[0038] The width between mountains can be designed in various ways, such as 600 - 1000 nm, 700 - 1000 nm, 800 - 1000 nm, 600 - 900 nm, 600 - 800 nm, 600 - 700 nm, etc.

[0039] The width between valleys can also be designed in the same way as the width between mountains.

[0040] The height difference between mountains and valleys (the height of mountains with respect to valleys as a reference) can be designed in various ways, such as 600 - 1000 nm, 700 - 1000 nm, 800 - 1000 nm, 600 - 900 nm, 600 - 800 nm, 600 - 700 nm, etc.

[0041] The distance between mountains, the distance between valleys, and the height difference between mountains and valleys in the pattern 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.

[0042] For example, the distance between mountains, the distance between valleys, and the height difference between mountains and valleys may be the same, such as 800 nm, 700 nm, or 600 nm, respectively. Also, the distance between mountains and the distance between valleys may be 800 nm, and the height difference between mountains and valleys may be 750 nm or 850 nm. Further, the distance between mountains and the distance between valleys may be 700 nm, and the height difference between mountains and valleys may be 650 nm or 750 nm.

[0043] The distance between mountains, the distance between valleys, and the height difference between mountains and valleys in the pattern can be changed by adjusting the size and spacing of the pattern formed on the mold used for manufacturing the support for cartilage regeneration.

[0044] The pattern has an area satisfying the uniformity (U) of the following Mathematical Formula 1 that 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.

[0045] [Mathematical Formula 1] U = |H P1 - H P2 | ≤ 0.1H n In the above formula, H P1 is the height at P1, H P2 is the height at P2, and H n means the height difference between mountains and valleys of a normal pattern.

[0046] Both P1 and P2 are either arbitrary points on the mountains of the pattern or arbitrary points on the valleys of the pattern.

[0047] For example, P1 and P2 may be points on the same mountain. P1 may be an arbitrary point on a mountain, and P2 may be a point on another mountain adjacent to that mountain, that is, a point on another mountain separated by one valley existing to the left or right of that mountain. Also, P1 may be an arbitrary point on a mountain, and P2 may be a point on a mountain separated from that mountain, that is, a point on another mountain separated by a plurality of valleys existing to the left or right of that mountain.

[0048] H P1 is the height at P1. The height at P1 means the height from the valley to P1 which is any point existing from the valley to the mountain top. If a mountain is formed at the intended height, H P1 is equal to the height of the pattern formed on the mold and is the difference in height between the mountain and valley of a normal pattern, H n being equal thereto. When the pattern formation is defective, H P1 is different from the height of the pattern formed on the mold.

[0049] H P2 is the height at P2. H P1 is the same as that.

[0050] The support for cartilage regeneration of the present invention has a difference in height between P1 and P2 that 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 of the difference in height between the mountain and valley of a normal pattern (H n ).

[0051] If the support for cartilage regeneration is excellent in thickness and pattern uniformity, cell proliferation of chondrocytes proceeds smoothly along the uniform pattern, showing an excellent effect for cartilage regeneration. When the pattern is not uniform and there is a partially damaged pattern, cell proliferation may stop at the damaged part of the pattern.

[0052] When P1 and P2 are points on the same mountain top, when measuring the pattern uniformity, optionally, the difference in height between P3 and P4 which are any points on the valley of the pattern may be additionally considered.

[0053] P3 and P4 may be points on the same valley. P3 is any point on the valley, and P4 may be another point on the valley adjacent to that valley, that is, a point on another valley existing across one mountain present on the left or right of that valley. Further, P3 is any point on the valley, and P4 may be a valley separated from that valley, that is, a point on another valley existing across a plurality of mountains present on the left or right of that valley.

[0054] When P1 and P2 are arbitrary points on the mountain and P3 and P4 are arbitrary points in the valley, U 1 =|H P1 -H P2 |≤0.1H n and U 2 =|H P3 -H P4 |≤0.1H n (H P3 is the height at P3, H P4 is the height at P4, H n means the height difference between the mountain and the valley in a normal pattern. The area satisfying () 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.)

[0055] The thickness of the support for cartilage regeneration is 30 - 100 μm, preferably 40 - 70 μm, and more preferably 50 - 60 μm. If the thickness is less than 30 μm, the mechanical strength (tensile strength and compressive strength) is low, and the support or the nanopattern formed on the support is likely to be damaged. If the thickness is more than 100 μm, the adhesion force decreases, and it becomes difficult to keep the support attached to the cartilage for a sufficient time required for cartilage regeneration.)

[0056] The tensile strength of the support for cartilage regeneration is 3 - 8 MPa, preferably 4 - 6 MPa. The elongation rate of the support for cartilage regeneration is 4 - 10%, preferably 5 - 7%. If the tensile strength is less than 3 MPa or the elongation rate exceeds 10%, the support is likely to be deformed, difficult to handle, and the patient may feel discomfort after the surgery. Also, if the tensile strength exceeds 8 MPa or the elongation rate is less than 4%, the support is likely to be damaged and has insufficient flexibility, so it may not adhere properly to the cartilage.)

[0057] The adhesion strength of the support for cartilage regeneration is 0.2 - 0.5 N / cm 2 and preferably 0.3 - 0.4 N / cm 2 and may be so.)

[0058] On one or both sides of the support for cartilage regeneration, any one or more selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs may be applied. The factors applied to the support can increase the cartilage regeneration rate by promoting cell growth.

[0059] Fibrin may be applied to the edge of the support for cartilage regeneration. The fibrin applied to the edge can form a fibrous thrombus and serve as a bridge for cell migration. This can facilitate cell migration and proliferation at the damaged site of cartilage and increase the cartilage regeneration rate.

[0060] The support 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 produce a sheet-like semi-cured product, applying pressure to the semi-cured product with a polydimethylsiloxane (PDMS) mold to produce a patterned semi-cured product, and drying the patterned semi-cured product.

[0061] The support 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 produce a sheet-like semi-cured product, positioning the semi-cured product between a polyurethane acrylate (PUA) mold and a polydimethylsiloxane (PDMS) mold, and then applying pressure with upper and lower plates to produce a patterned semi-cured product, and drying the patterned semi-cured product.

[0062] The polyurethane acrylate (PUA) mold and / or the polydimethylsiloxane (PDMS) mold has irregularities for forming a pattern on one side and / or both sides of the support.

[0063] More specifically, the support for cartilage regeneration can be manufactured by a method including the following steps: a semi-cured product formation step (S100), a semi-cured product fixing step (S200), a conveying step (S300), a pressing step (S400), a drying step (S500), and a separating step (S600).

[0064] Referring to FIGS. 12 and 15(A), the semi-cured product formation step (S100) can include a step (S110) of disposing 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 can be disposed on a load region LA. In the present embodiment, the case where the base is the lower plate 510 will be exemplified and described.

[0065] The upper mold 900 is a polyurethane acrylate (PUA) mold.

[0066] The upper mold 900 can 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 can be fixed on the base surface.

[0067] The first pattern surface 910 can include a pattern of a predetermined shape. The pattern is not limited to a specific shape as long as it is a shape in which mountains and valleys are repeated. The pattern may be, for example, linear or curved in which mountains and valleys are arranged and repeated. The shape of the pattern may be a straight line parallel to any one edge of the support for cartilage regeneration, a diagonal line forming a predetermined angle with any one edge, a wavy curve, or the like.

[0068] The width between mountains can be designed in various ways according to the pattern of the support for cartilage regeneration to be manufactured, for example, 600 - 1000 nm, 700 - 1000 nm, 800 - 1000 nm, 600 - 900 nm, 600 - 800 nm, 600 - 700 nm, etc.

[0069] The width between valleys can be designed in the same way as the width between mountains.

[0070] The height difference between mountains and valleys (the height of mountains based on valleys) can be designed in various ways according to the pattern of the cartilage regeneration support to be manufactured, such as 600 - 1000 nm, 700 - 1000 nm, 800 - 1000 nm, 600 - 900 nm, 600 - 800 nm, 600 - 700 nm, etc.

[0071] The distance between mountains, the distance between valleys, and the height difference between mountains and valleys in the pattern 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.

[0072] For example, the distance between mountains, the distance between valleys, and the height difference between mountains and valleys may be the same, such as 800 nm, 700 nm, or 600 nm, respectively. Also, the distance between mountains and the distance between valleys may be 800 nm, and the height difference between mountains and valleys may be 750 nm or 850 nm. Furthermore, the distance between mountains and the distance between valleys may be 700 nm, and the height difference between mountains and valleys may be 650 nm or 750 nm.

[0073] By adjusting the size and spacing of the pattern formed on the mold, the size and spacing of the pattern of the cartilage regeneration support to be manufactured can be changed.

[0074] Referring to FIGS. 12 and 15(B), the step (S100) of forming the semi - cured product 1000b may include the step (S120) of applying the 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 - cured product 1000b can be formed.

[0075] The biocompatible polymer solution can be produced by mixing a biocompatible polymer and an organic solvent. As the organic solvent, for example, solvents of halomethanes such as chloroform or dichloromethane can be used.

[0076] The appropriate concentration of the biocompatible polymer solution can vary depending on the type of the biocompatible polymer. 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).

[0077] In the process of applying the biocompatible polymer solution 1000a, the solvent partially evaporates at room temperature to form a sheet-like semi-cured product 1000b, so that even if the upper mold 900 is turned over, the semi-cured product does not flow down.

[0078] In this way, the upper mold 900 on which the semi-cured product 1000b is disposed on the first pattern surface 910 is called the first mold 1100.

[0079] Since the semi-cured product 1000b is disposed on the upper mold 900 of the first mold 1100, it is necessary to turn over the first mold 1100 later and bring it into contact with the lower mold 800.

[0080] Therefore, in order to bring the surface of the semi-cured product 1000b exposed by turning over the first mold 1100 into contact with the lower mold 800, a high-viscosity biocompatible polymer can be used, or a highly volatile solvent can be used to quickly evaporate the solvent, thereby increasing the viscosity of the semi-cured product 1000b so that it does not flow down.

[0081] Referring to FIG. 11, the method for manufacturing a support for cartilage regeneration according to the present invention can include a step (S200) of fixing a semi-cured product 1000b. The fixing of the semi-cured product 1000b is a step of turning over the first mold 1100 and bringing the exposed semi-cured product 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 the second mold 1200.

[0082] The lower mold 800 is a polydimethylsiloxane (PDMS) mold.

[0083] Referring to FIGS. 13 and 16(A), the step (S200) of fixing the semi-cured product 1000b can include a step (S210) of placing a carrier 320 on a loading area LA.

[0084] A lower plate 510 can be placed on the carrier 320. For example, the lower surface 512 of the lower plate can be fixed to the carrier fixing surface 328. Accordingly, on the loading area LA, the lower plate 510 can be arranged such that the upper surface 517 of the lower plate is exposed.

[0085] Referring to FIGS. 13 and 16(B), the step (S200) of fixing the semi-cured product 1000b can include a step (S220) of placing the lower mold 800 on the lower plate 510. For example, on the loading area LA, the lower mold 800 can be placed on the upper surface 517 of the lower plate.

[0086] The lower mold 800 can include a flat surface without a pattern and a second support surface 860 formed on a surface opposite to the flat surface. The second support surface 860 can be fixed to the upper surface 517 of the lower plate. Thereby, on the loading area LA, when the lower mold 800 is placed on the lower plate 510, the flat surface can be exposed to the outside. The lower mold 800 having a flat surface without a pattern is used for manufacturing a support for cartilage regeneration with a single-sided nanopattern.

[0087] The lower mold 800 can include a second pattern surface 810 and a second support surface 860 formed on a surface opposite to 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. In the case of a flat surface without a pattern, it is used to manufacture a support for single-sided pattern cartilage regeneration, and in the case of a surface with a pattern formed thereon, it is used to manufacture a support for double-sided pattern cartilage regeneration. The second support surface 860 can be fixed to the upper surface 517 of the lower plate. Thereby, when the lower mold 800 is disposed on the lower plate 510 in the load region LA, the second pattern surface 810 can be exposed to the outside.

[0088] Referring to FIGS. 13 and 16(C), the step (S200) of fixing the semi-cured product 1000b can include the step (S230) of bringing the first mold 1100 into contact with the lower mold 800. For example, the first mold 1100 can be disposed such that the semi-cured product 1000b contacts the second pattern surface 810 to fix the semi-cured product.

[0089] The step (S200) of fixing the semi-cured product 1000b can expose the first support surface 960 of the upper mold 900 to the outside in the load region LA.

[0090] Referring to FIGS. 11 and 17, a method for manufacturing a support for cartilage regeneration according to an embodiment of the present invention can include a conveying step (S300) of conveying the second mold 1200.

[0091] The conveying step (S300) can move the second mold 1200 disposed in the load region LA to the molding region PA.

[0092] Above the forming area PA, the pressing plate 430 of the pressing unit 400 can be arranged. The upper plate 520 can be coupled to the pressing plate 430. Thereby, the second mold 1200 can be arranged below the upper plate 520.

[0093] For example, the pressing plate 430 can include a pressing plate lower surface 432 and a pressing plate upper surface 437. The upper plate 520 can be coupled to the pressing plate lower surface 432.

[0094] The upper plate 520 can include an upper plate pressing surface 522 and an upper plate coupling surface 527. The upper plate coupling surface 527 can be coupled to the pressing plate lower surface 432. And the pressure dispersion part 550 can be adhered to the upper plate pressing surface 522.

[0095] Below the forming area PA, a conveying unit 300 for moving and conveying the second mold 1200 and a lower plate 510 arranged on the conveying unit 300 can be arranged.

[0096] For example, the conveying unit 300 can include a conveying rail 310 and a carrier 320. The lower plate 510 can be arranged on the carrier 320. The second mold 1200 can be arranged on the lower plate 510. Thereby, the second mold 1200 can be arranged in the forming area PA.

[0097] And the conveying unit 300 can further include a conveying drive part 330 for moving the carrier 320. By driving the conveying drive part 330, the carrier 320 can be moved from the loading area LA to the forming area PA.

[0098] Therefore, in the forming region PA, the second mold 1200 can be disposed downward of the pressure dispersion portion 550. For example, in the conveying step (S300), in the forming region PA, the pressure dispersion portion 550 and the first support surface 960 which is the exposed surface of the second mold 1200 can be disposed to face each other.

[0099] Referring to FIG. 11, a method for manufacturing a cartilage regeneration support according to an embodiment of the present invention may include a pressing step (S400) of pressing a fixed semi-cured product 1000b.

[0100] For example, referring to FIGS. 14 and 18(A), the pressing step (S400) can be performed in the forming region PA.

[0101] The pressing step (S400) of pressing the fixed semi-cured product 1000b may include a step (S410) of bringing the upper plate 520 into contact with the second mold 1200. For example, the upper plate pressing surface 522 of the upper plate 520 can be brought into contact with the first support surface 960 of the upper mold 900. As a specific example, in the step (S410) of bringing the upper plate 520 into contact, the pressure dispersion portion 550 can be brought into contact with the first support surface 960.

[0102] The step (S410) of bringing the upper plate 520 into contact with the second mold 1200 may include a step of operating the pressing unit 400. For example, the pressing unit 400 can operate an actuator disposed in the pressing unit main body 410. An actuator rod 420 can be connected to the actuator. The actuator rod 420 can move in the direction of the pressing plate 430. The actuator rod 420 can be fixed to a fixing portion 439 disposed on one surface of the pressing plate 430.

[0103] The pressing rod 420 can move in the vertical direction. When the pressing rod 420 moves downward, the upper plate 520 coupled to the pressing plate 430 can move downward. Therefore, the upper plate 520 can move in the direction of the lower plate 510.

[0104] The upper plate 520 can be moved to bring the upper plate pressing surface 522 into contact with the second mold 1200 disposed on the lower plate 510. More specifically, the pressure dispersion part 550 can be brought into contact with the first support surface 960 of the upper mold 900 exposed in the second mold 1200.

[0105] In the step (S410) of bringing the upper plate 520 into contact with the second mold 1200, the thickness of some regions of the second mold 1200 may be different from that of other regions.

[0106] The difference in thickness may occur, for example, when the biocompatible polymer solution 1000a is unevenly arranged in the coating process of the biocompatible polymer solution 1000a. Alternatively, the difference in thickness may also occur in the formed thickness of the upper mold 900 and the lower mold 800.

[0107] When the difference in thickness occurs, the upper plate 520 may tilt and the entire surface of the pressure dispersion part 550 and the entire surface of the first support surface 960 may not be in surface contact.

[0108] Referring to FIGS. 14 and 18(B), the pressing step (S400) can include a step (S420) of adjusting the tilt of the upper plate 520.

[0109] The step (S420) of adjusting the tilt can bring the upper plate 520 and the semi-cured product 1000b fixed thereto into surface contact. For example, the step (S420) of adjusting the tilt of the upper plate 520 can bring the entire surface of the pressure dispersion part 550 and the entire surface of the first support surface 960 into surface contact.

[0110] After bringing the two components into surface contact, it is possible to perform a step of leveling the upper plate 520. That is, rotation (tilt adjustment) of the upper plate 520 can be performed.

[0111] The tilt of the upper plate 520 can be adjusted by the gimbal part 450. The gimbal part 450 can be arranged on the upper surface of the pressure plate 430. For example, the gimbal part 450 can be arranged between the guide rod 440 formed on the pressurizing unit 400 and the pressure plate 430. Also, the gimbal part 450 can be arranged between the fixing part 439 and the pressure plate 430.

[0112] When the tilt of the upper plate 520 is not horizontal, the gimbal part 450 can rotate the upper plate 520 to level the upper plate 520.

[0113] Therefore, the gimbal part 450 can provide the load of the upper plate 520 to the region where the thickness difference of the second mold 1200 occurs. For example, the gimbal part 450 can rotate (tilt) the upper plate 520 to provide a load to the region where the thickness difference occurs in order 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.

[0114] The loads of the upper plate 520 and the pressure plate 430 provided to the second mold 1200 can provide pressure to the fixed semi-cured product 1000b. Thereby, the loads of the upper plate 520 and the pressure plate 430 can pressurize the fixed semi-cured product 1000b in the region where the thickness difference occurs.

[0115] When the upper plate 520 becomes horizontal, the gimbal part 450 can stop applying a load to the second mold 1200.

[0116] Referring to FIGS. 14 and 19, it can include a step (S430) of maintaining a pressing force on the pressing plate 430.

[0117] The step (S430) of maintaining the pressing force can be performed in a state where the pressure dispersion part 550 and the first support surface 960 are in surface contact and the upper plate 520 is horizontal.

[0118] In the above state, the target pressing force can be maintained on the pressing plate 430. In the step (S430) of maintaining the pressing force, a pressing force of 0.40 Pa to 0.70 Pa, preferably a pressing force of 0.45 to 0.65 MPa, can be provided to the pressing plate 430. The providing time of the pressing force varies depending on the magnitude of the pressing force. For example, it can be provided with a maintaining time of 30 minutes to 50 minutes.

[0119] 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-cured product 1000b.

[0120] Due to the pressing force provided to the second mold 1200, the pattern shapes formed on the first pattern surface 910 and the second pattern surface 810 can be transferred to the semi-cured product 1000b.

[0121] Referring to FIGS. 11 and 20, it can include a drying step (S500) of drying the semi-cured product 1000b.

[0122] In the drying step (S500), target drying heat can be provided to the second mold 1200 through the lower plate 510. Alternatively, the second mold 1200 can be dried with a drying oven or a hot plate, and as a result, the semi-cured product 1000b can be dried.

[0123] When drying the second mold 1200 through the lower plate 510, a heating plate can be provided inside the lower plate 510. The heating plate can transfer thermal energy to the upper surface 517 of the lower plate to dry the second mold 1200. The thermal energy transferred to the second mold 1200 can be transferred to the semi-cured product 1000b to dry the semi-cured product 1000b.

[0124] On the other hand, when drying the second mold 1200 in a drying oven, the carrier 320 can be moved from the molding area PA to the loading area LA, and the second mold 1200 loaded on the lower plate 510 can be handled in the loading area LA. The second mold 1200 is handled and loaded into the drying oven DO, and the drying heat can be provided to the second mold 1200.

[0125] Here, in the drying step (S500), thermal energy of 15°C to 45°C can be provided to the second mold 1200 for 6 hours to 10 hours.

[0126] On the other hand, in the drying step (S500), the second mold 1200 can be positioned on a hot plate for drying. When using a hot plate, a steel plate of 0.5 Kg to 2 Kg can be laminated on the second mold 1200, and the hot plate can be heated to 60°C to 80°C to dry the second mold 1200. The second mold 1200 can be dried by maintaining the heating temperature for 4 hours to 8 hours.

[0127] Here, the steel plate can prevent the upper mold 900 or the lower mold 800 from being separated from the semi-cured product 1000b during the drying process.

[0128] If the upper mold 900 or the lower mold 800 is separated during the drying process, the surface pattern of the semi-cured product 1000b may be damaged. Therefore, in order to prevent damage to the surface pattern of the semi-cured product 1000b, the step of disposing the steel plate on the second mold 1200 for drying can be performed.

[0129] Thus, by drying the second mold 1200, a cured cartilage regeneration support 1000 can be formed between the upper mold 900 and the lower mold 800.

[0130] Referring to FIGS. 11 and 20, a step (S600) of separating the cartilage regeneration support 1000 from the second mold 1200 can be performed.

[0131] 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.

[0132] After the separation step (S600), the biological support 1000 can be immersed in 70% ethanol for 10 seconds and rinsed with purified water.

[0133] The method for manufacturing a cartilage regeneration support of the present invention can be performed using a manufacturing apparatus 10 for a cartilage regeneration support as follows. Hereinafter, the manufacturing apparatus for a cartilage regeneration support will be shown and described in detail.

[0134] FIG. 3 is a perspective view of a manufacturing apparatus for a cartilage regeneration support according to an embodiment of the present invention, FIG. 4 is a front view of a manufacturing apparatus for a cartilage regeneration support according to an embodiment of the present invention, FIG. 5 is a top view of a manufacturing apparatus for a cartilage regeneration support according to an embodiment of the present invention, and FIG. 6 is a cross-sectional view taken along “A1 - A2” of FIG. 5.

[0135] Referring to FIGS. 3 to 6, the manufacturing apparatus 10 for a cartilage regeneration support can include a pedestal 100.

[0136] The pedestal 100 can include a pedestal body 110 and a table 120.

[0137] Table 120 can be formed of a plate having a flat surface. A plurality of components can be arranged on table 120. The flat surface can provide a stable fixing surface for the components.

[0138] The pedestal body 110 can be provided with a plurality of legs. The plurality of legs can be arranged at the corners of table 120. The plurality of legs may be arranged with different set lengths or the same set length. The plurality of legs with adjusted set lengths can form the flat surface of table 120.

[0139] Also, the plurality of legs can be arranged with a set length corresponding to the working height of the operator. For example, the plurality of legs can be arranged at the expected working height of the operator. The plurality of legs with adjusted height can improve the workability of the operator.

[0140] The manufacturing apparatus 10 for a cartilage regeneration support can include a frame unit 200. The frame unit 200 can be arranged on table 120. The frame unit 200 can include a frame support base 220 and a frame body 210.

[0141] The frame support base 220 can support the frame body 210. The frame support base 220 can be arranged on the upper surface of table 120. The frame support base 220 is installed on table 120 and can fix the frame body 210. The frame support base 220 and table 120 can be fixed by a coupling structure such as fixing screws, but the fixing means is not limited to fixing screws. Also, the frame support base 220 and the frame body 210 can be fixed by the same fixing means.

[0142] The frame body 210 can be arranged on the table 120. For example, the frame body 210 can be located above the upper surface of the table 120 and supported by the frame support 220. The frame body 210 can be arranged in a plate shape. Therefore, the frame body 210 can be arranged in a direction parallel to the flat surface of the table 120.

[0143] The frame body 210 can be provided with a plurality of through holes 212, 215. Cylinder guides 213, 216 can be respectively arranged on the plurality of through holes 212, 215 of the frame body 210.

[0144] The plurality of through holes 212, 215 can include a first through hole 212 and a second through hole 215. A guide rod 440 can be arranged in the first through hole 212. A pressure rod 420 can be arranged in the second through hole 215.

[0145] A plurality of the first through holes 212 can be arranged around the second through hole 215. The first through holes 212 can be arranged symmetrically around the second through hole 215.

[0146] In this embodiment, a case where two first through holes 212 are arranged symmetrically around the second through hole 215 will be exemplified and described. However, the arrangement of the first through holes 212 is not limited to this, and 3 to 8 first through holes 212 may be arranged symmetrically around the second through hole 215.

[0147] The guide rod 440 can disperse the concentrated pressure provided from the pressure rod 420 in the surface direction of the pressure plate 430. Therefore, since the number of the arranged first through holes 212 is related to the number of the arranged guide rods 440, it can play a role in forming the pressure dispersed on the pressure plate 430. The pressure plate 430 with the dispersed pressure formed can help to form a uniform surface pressure on the molding unit 500.

[0148] The manufacturing apparatus 10 for a cartilage regeneration support can include a conveyance unit 300.

[0149] Here, for ease of explanation, in the table 120, the region accommodated in the frame support base 220 and the frame body 210 is defined as a forming region PA, and the region other than the forming region PA is defined as a peripheral region SA. In the peripheral region SA, the region where the conveyance unit 300 is arranged is defined as a load region LA.

[0150] The conveyance unit 300 can include a conveyance rail 310, a carrier 320, and a conveyance drive unit 330.

[0151] The conveyance rail 310 can be arranged on the upper surface of the table 120. The conveyance rail 310 can be arranged from the load region LA to the forming region PA. The conveyance rail 310 can form a rail part with a pair of rails arranged in the direction from the load region LA to the forming region PA. At least one or more of the rail parts can be arranged. For example, when the conveyance rail 310 has a plurality of rail parts formed in the direction from the load region LA to the forming region PA, the load region LA can form a plurality of working ports.

[0152] The carrier 320 can be arranged on the conveyance rail 310. The carrier 320 can move along the conveyance rail 310. Therefore, the carrier 320 can be arranged in the load region LA and the forming region PA.

[0153] The carrier 320 can be movably coupled to the conveyance rail 310. For example, the carrier 320 can be slidably coupled to the conveyance rail 310, but is not limited thereto, and as long as it is a movable means, the carrier 320 can be coupled to the conveyance rail 310 in any structure.

[0154] The carrier 320 can include a sliding portion 322 having a sliding structure and a fixing surface 328 disposed on a surface opposite to the sliding portion 322. The sliding portion 322 can be coupled to the transport rail 310. The lower plate 510 can be fixed to the fixing surface 328. The fixing surface 328 can face the lower plate 510.

[0155] The carrier 320 can be connected to the transport drive unit 330. The transport drive unit 330 can be connected to a thickness surface formed between the sliding portion 322 and the fixing surface 328.

[0156] The transport drive unit 330 can be disposed in the peripheral region SA. An actuator is disposed in the transport drive unit 330, and the carrier 320 can be moved to the loading region LA and the forming region PA. In the present embodiment, a structure in which the actuator moves back and forth will be described as an example, but in some cases, the carrier 320 can be moved by a structure that moves left and right.

[0157] The manufacturing apparatus 10 for a cartilage regeneration support can include a pressing unit 400. The pressing unit 400 can be disposed on the forming region PA. The pressing unit 400 can include a pressing unit main body 410, a pressing rod 420, a pressing plate 430, and a guide rod 440.

[0158] The pressing unit main body 410 can be disposed on the upper surface of the frame main body 210. The pressing unit main body 410 can include an actuator. The actuator can move the pressing rod 420 in the vertical direction.

[0159] The pressing rod 420 can be disposed in a second through hole 215 that penetrates the upper and lower surfaces of the frame main body 210. For example, the pressing rod 420 can be fitted into a second cylinder guide 216 disposed in the second through hole 215.

[0160] The pressing rod 420 can move in the vertical direction. The pressing rod 420 can move and contact the pressing plate 430. The pressing rod 420 can move the pressing plate 430 downward. When the pressing rod 420 faces the object to be molded in the target area, it can provide pressure to the pressing plate 430.

[0161] The pressing unit 400 can include a pressing plate 430 disposed between the frame body 210 and the table 120.

[0162] The pressing plate 430 can include a top surface 437 of the pressing plate where the pressing rod 420 contacts. The top surface 437 of the pressing plate can be provided with a fixing portion 439. The pressing rod 420 can be fixed to the fixing portion 439.

[0163] The fixing portion 439 can be disposed in a region including the center of gravity of the pressing plate 430. For example, when the pressing plate 430 is arranged in a square shape, the center of gravity of the pressing plate 430 can be in the central region of the square. Therefore, the fixing portion 439 can be disposed on the central region.

[0164] One end of the pressing rod 420 can be fixed to the fixing portion 439. The fixing portion 439 can be formed of a material such as rubber or silicon that can withstand the pressing force on the top surface 438 of the pressing plate.

[0165] In this way, when the pressing rod 420 moves downward, the pressing rod 420 can move the pressing plate 430 downward. And when the pressing plate 430 moves to the target position, the pressing rod 420 can provide a pressing force to the center of gravity of the pressing plate 430.

[0166] A guide rod 440 can be disposed around the pressing rod 420. The guide rod 440 can be disposed between the frame body 210 and the pressing plate 430.

[0167] 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 part of the frame body 210. For example, a first cylinder guide 213 can be disposed 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.

[0168] As described above, a plurality of the first through holes 212 can be symmetrically arranged around the periphery of the second through hole 215. The guide rods 440 can be respectively disposed in the plurality of first through holes 212.

[0169] Therefore, the plurality of guide rods 440 can be symmetrically arranged around the pressure rod 420. The plurality of guide rods 440 can serve to disperse the pressing force so that the forming unit 500 can form a uniform surface pressure. The plurality of guide rods 440 can form a uniform pressing force over the entire surface of the pressure plate 430.

[0170] On the other hand, a gimbal member 450 can be disposed between the guide rod 440 and the pressure plate 430. For example, the gimbal member 450 can connect the lower surface of the guide rod 440 and the upper surface of the pressure plate. Also, the gimbal member 450 can be selectively disposed between the fixing portion 439 and the pressure plate 430. The gimbal member 450 can connect the lower surface of the fixing portion 439 and the upper surface of the pressure plate 430.

[0171] The gimbal members 450 can be symmetrically arranged around the fixing portion 439 and around the periphery of the fixing portion 439. In other words, on the upper surface of the pressure plate 430, by arranging a plurality of guide rods 440 around the periphery of the region including the center of gravity of the pressure plate 430, the gimbal members 450 arranged on each of the plurality of guide rods 440 can also be arranged in the same arrangement structure.

[0172] The gimbal part 450 can adjust the inclination of the pressure plate 430. For example, the gimbal part 450 can align the upper plate 520 horizontally. That is, the gimbal part 450 can rotate (adjust the inclination) of the upper plate 520.

[0173] When the inclination of the upper plate 520 is not horizontal, the gimbal part 450 can rotate the upper plate 520 to align the upper plate 520 horizontally.

[0174] Therefore, since the gimbal part 450 rotates (tilts) the upper plate 520 to align it horizontally, the load of the upper plate 520 can be provided to the second mold ("1200" in 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.

[0175] The gimbal part 450 can adjust the pressure imbalance that may occur due to the difference in the thickness of the object to be molded. For example, when the thickness of the object to be molded is different, the gimbal part 450 can adjust the inclination of the pressure plate 430 so that the pressure plate 430 corresponds to the entire surface of one surface of the object to be molded.

[0176] Therefore, when the thickness of a part of the object to be molded is different from the thickness of other regions, the gimbal part 450 can adjust the pressure plate 430 so that the pressure does not concentrate on a part of the object to be molded or unnecessary pressure is not transmitted.

[0177] In this way, the gimbal part 450 can adjust the inclination of the pressure plate 430 to improve the molding uniformity of the object to be molded.

[0178] The manufacturing apparatus 10 for the cartilage regeneration support can include a molding unit 500. The molding unit 500 can include a lower plate 510, an upper plate 520, and a pressure dispersion part 550.

[0179] The lower plate 510 can be disposed on the upper surface of the carrier 320. For example, the lower plate 510 can be fixed to the fixing surface 328 of the carrier 320. The lower plate 510 can be formed in a shape similar to that of the carrier 320 or a shape smaller than that of the carrier 320.

[0180] The lower surface 512 of the lower plate 510 can be fixed to the fixing surface 328 of the carrier 320. The carrier 320 can move between the load region LA and the molding region PA along the transport rail 310. Accordingly, the lower plate 510 fixed to the carrier 320 can move between the load region LA and the molding region PA via the carrier 320.

[0181] The lower plate 510 can include an upper surface 517 of the lower plate 510 on a surface opposite to the lower surface 512 of the lower plate 510. A lower mold ("800" in FIG. 18) can be disposed on the upper surface 517 of the lower plate 510. The lower mold 800 will be described in detail in the manufacturing method.

[0182] The upper plate 520 can be disposed in the molding region PA. The upper plate 520 can be coupled to the pressing plate 430. The upper plate 520 can include an upper plate coupling surface 527 that is coupled to the pressing plate 430. For example, the upper plate coupling surface 527 can be coupled to the lower surface 432 of the pressing plate 430. The lower surface 432 of the pressing plate can be a surface facing the upper surface 437 of the pressing plate where the fixing portion 439 is disposed.

[0183] The shape of the upper plate 520 can be formed into a shape with a larger area than the shape of the lower plate 510. An object to be molded can be disposed between the upper plate 520 and the lower plate 510. Since the area of the upper plate 520 is larger than the shape of the lower plate 510, a uniform pressure can be provided to the object to be molded. Therefore, the size of the object to be molded can be limited by the shape of the lower plate 510.

[0184] As described above, since the manufacturing apparatus 10 for a cartilage regeneration support according to the present invention can form a pressure plate 430 that disperses the applied pressure and makes the applied pressure uniform, the area of the lower plate 510 can be increased. Therefore, an object to be molded disposed on the lower plate 510 can be formed with a large area.

[0185] The upper plate 520 can include an upper plate pressure surface 522 on a surface opposite to the upper plate coupling surface 527. A pressure dispersion portion 550 can be disposed on the upper plate pressure surface 522.

[0186] The pressure dispersion portion 550 can be adhered to the upper plate pressure surface 522 via an adhesive. The pressure dispersion portion 550 can be formed of a silicon material, but is not limited thereto, and any material can be used as long as it can transmit pressure. The pressure dispersion portion 550 can evenly disperse the applied pressure input from the pressure plate 430 over the entire surface of the upper plate 520.

[0187] The manufacturing apparatus 10 for a cartilage regeneration support can include an input unit 600 and a display unit 700. The input unit 600 and the display unit 700 can be disposed in the peripheral region SA.

[0188] The manufacturing apparatus 10 for a cartilage regeneration support can include an input unit 600 that receives an input from an operator. For example, the operator can directly input a set value into the input unit 600.

[0189] The input unit 600 can include input means such as input buttons for inputting set values. Here, examples of the set values include the pressure of the pressurizing unit 400, the heating temperature of the lower plate 510, the pressure supply time and the heating time of the pressurizing unit 400, and the like.

[0190] The display unit 700 can display the set value on the screen. In other words, the display unit 700 can display the 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 supply time, and the heating time, etc. numerically.

[0191] In addition, in the space where the display unit 700 is arranged, a control unit capable of controlling the set value of the manufacturing apparatus 10 for the cartilage regeneration support can be further arranged.

[0192] Thus, since the manufacturing apparatus 10 for the cartilage regeneration support according to the embodiment of the present invention forms a uniform pressure, a cartilage regeneration support with improved uniformity can be manufactured.

[0193] FIG. 7 is a block diagram showing a manufacturing apparatus for a cartilage regeneration support according to an embodiment of the present invention.

[0194] Regarding FIG. 7, in order to avoid redundant explanations and facilitate the explanation, reference will be made to FIGS. 3 to 6 for the explanation.

[0195] The manufacturing apparatus 10 for a cartilage regeneration support according to an embodiment of the present invention can include a sensor unit 30 and a control unit 50.

[0196] 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 arranged in the area where the display unit 700 is arranged.

[0197] The control unit 50 can also be connected to the configuration where the sensor unit 30 is arranged. For example, the control unit 50 can be connected to the configuration where the pressure sensor 470 and / or the temperature sensor 515 are arranged.

[0198] As a specific example, when the temperature sensor 515 is arranged on the lower plate 510, the control unit 50 can be connected to the lower plate 510. As another example, when the pressure sensor 470 is arranged in the pressurizing unit 400, the control unit 50 can be connected to the pressurizing unit 400. The sensor unit 30 can include the pressure sensor 470. The pressure sensor 470 can be arranged on the upper surface of the frame body 210.

[0199] In this figure, the case where the pressure sensor 470 is arranged in the pressurizing unit 400 will be exemplified and described. Here, the pressure sensor 470 can also be arranged in the molding unit 500.

[0200] The input unit 600 can receive an input from an operator. The input unit 600 can input the applied pressure to the pressure rod 420 of the pressurizing unit 400. The input provided may be the set pressure at which the pressurizing unit 400 operates. The input unit 600 can form a first signal SG1 consisting of the set pressure.

[0201] The input unit 600 can provide the 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.

[0202] The control unit 50 can convert the first signal SG1 and transmit a first-1 signal SG11 to the display unit 700. The display unit 700 that has received the first-1 signal SG11 can display the set pressure on the screen.

[0203] Also, the control unit 50 can convert the first signal SG1 and transmit a first-2 signal SG12 to the pressurizing unit 400.

[0204] 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 in response to the first-second signal SG12 and contacts the object to be formed, the pressurizing rod 420 can provide pressure to the pressurizing plate 430.

[0205] 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 the second signal SG2 using the information sensed about the pressure formed in the pressurizing unit 400. The sensor unit 30 can transmit the second signal SG2 to the control unit 50.

[0206] The control unit 50 that has received the second signal SG2 can calculate whether the pressure has been transmitted via the pressurizing unit 400 according to the information corresponding to the first-second signal SG12. For example, the control unit 50 can calculate the difference between the pressure set on the pressurizing 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 pressure difference (hereinafter, "calculated value").

[0207] When the calculated value is within the error range compared with the pre-measured data, the control unit 50 can transmit the fourth signal SG4 to the display unit 700. Then, the control unit 50 can generate the third signal SG3 that is the same as the first-second signal SG12 and provide the third signal SG3 to the pressurizing unit 400.

[0208] On the other hand, when the calculated value is outside the error range compared with the pre-measured data, the control unit 50 can provide the corrected input value to the pressurizing unit 400.

[0209] Here, when the control unit 50 is manually set, the fourth signal SG4 composed of the calculated value can be transmitted to the display unit 700. The display unit 700 can display the calculated value corresponding to the fourth signal SG4 on the screen.

[0210] The operator can check the calculated value displayed on the display unit 700. Based on the displayed information, the operator can input the corrected input value into the input unit 600.

[0211] The control unit 50 can generate the 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. The pressurizing unit 400 can provide the corrected pressure value to the pressurizing plate 430 via the third signal SG3. The corrected pressure value may be the pressure provided to the pressurizing plate 430.

[0212] Also, the control unit 50 can generate a fourth - 1 signal SG4 - 1 based on the information corresponding to the third signal SG3. The fourth - 1 signal SG4 - 1 can be provided to the display unit 700. The display unit 700 can display the information composed of the fourth - 1 signal SG4 - 1 on the screen.

[0213] Thus, the manufacturing apparatus 10 for the cartilage regeneration support according to the present invention can control the pressure provided to the pressurizing unit 400 via the sensor unit 30.

[0214] On the other hand, when the control unit 50 is automatically set, if there is a difference in the value obtained by calculating the pressure difference (hereinafter, "calculated value"), it may not be necessary to generate the fourth signal SG4.

[0215] The pressure sensor 470 can sense the pressure formed in the pressurizing unit 400. The sensor unit 30 can generate a second - 1 signal SG21 based on the sensing information. The sensor unit 30 can transmit the second - 1 signal SG21 to the control unit 50.

[0216] Based on the pre-measured data, the control unit 50 can determine whether the calculated value is within the error range compared with the pre-measured data. When it is determined that the value is within the error range, the control unit 50 can generate the same third signal SG3 as the first-second signal SG12.

[0217] The third signal SG3 formed by the control unit 50 can be transmitted to the pressurizing unit 400. The pressurizing unit 400 can provide a pressure corresponding to the first-second signal SG12 to the pressurizing plate 430 via the third signal SG3. The pressure corresponding to the first-second signal SG12 may be the pressure provided to the pressurizing plate 430.

[0218] Also, the control unit 50 can generate a fourth signal SG4 based on the information corresponding to the third signal SG3. The fourth signal SG4 can be provided to the display unit 700. The display unit 700 can display the information consisting of the fourth signal SG4 on the screen.

[0219] In this way, the manufacturing apparatus 10 for the cartilage regeneration support according to the present invention can control the pressure provided to the pressurizing unit 400 via the sensor unit 30.

[0220] On the other hand, the control unit 50 can compare the input pressure with the pressure provided to the object to be molded. For example, the pressurizing unit 400 can provide pressure to the molding unit 500. For example, the pressurizing unit 400 can transmit the pressure formed on the pressurizing plate 430 to the molding unit 500.

[0221] A difference may occur between the pressure formed by the pressurizing unit 400 and the pressure formed by the molding unit 500. The control unit 50 can compare the pressure supplied from the pressurizing unit 400 with the pressure output from the molding unit 500. The output pressure may be the pressure provided to the object to be molded.

[0222] The provided pressure can be provided to the molding unit 500 via the pressing plate 430. Through the molding unit 500, the output pressure provided to the object to be molded can be formed.

[0223] The pressure sensor 470 of the sensor unit 30 can be arranged in each of the pressurizing unit 400 and the molding unit 500. The pressure sensor 470 can sense the provided pressure of the pressurizing unit 400. Also, the pressure sensor 470 can sense the output pressure of the molding unit 500.

[0224] The sensor unit 30 can generate a second signal composed of the provided pressure and the output pressure.

[0225] A difference (hereinafter, "pressure difference") may occur between the provided pressure input from the pressing rod 420 and the output pressure output from the molding unit 500. For example, a pressure difference may occur in the process of dispersing the pressure over the entire surface of the pressing plate 430 or in the process of dispersing the pressure by the pressure dispersion unit 550.

[0226] In this case, the probability of defective molding of the molded product may increase. Also, losses due to leakage of the electric power used in the manufacturing apparatus may occur.

[0227] The pressure sensor 470 senses the pressure in each set region, and the sensor unit 30 can change the pressure in each set region into a signal and transmit the second signal SG2 to the control unit 50.

[0228] The control unit 50 can calculate the pressure difference. Based on the calculated value, the set value of the pressurizing unit 400 can be readjusted. Also, the coupling structure between each component can be readjusted. Therefore, the pressure sensor 470 can reduce the probability of occurrence of defects and reduce the losses due to leakage of the electric power used in the manufacturing apparatus.

[0229] FIG. 8 is a plan view showing the shape of the pressing plate of the pressing unit according to an embodiment of the present invention, FIG. 9 is a plan view showing another shape of the pressing plate of the pressing unit according to an embodiment of the present invention, and FIG. 10 is a plan view showing still another shape of the pressing plate of the pressing unit according to an embodiment of the present invention.

[0230] Regarding FIGS. 8 to 10, in order to avoid redundant explanations and facilitate the explanation, reference will be made to FIGS. 3 to 6 for the explanation.

[0231] Referring to FIGS. 8 to 10, the pressing unit 400 can include a pressing rod 420, a pressing plate 430, and a guide rod 440.

[0232] The pressing plate 430 can include a fixing portion 439. The fixing portion 439 can be disposed in a region including the center of gravity of the pressing plate 430. The pressing rod 420 can be disposed at a position corresponding to the fixing portion 439.

[0233] The guide rod 440 can be disposed around the pressing rod 420. The guide rod 440 can be symmetrically disposed around the pressing rod 420. The symmetrically disposed guide rods 440 can form a pressing force distributed over the entire surface of the pressing plate 430.

[0234] On the other hand, the lower plate 510 of the molding unit 500 can be arranged in a shape with an area smaller than that of the upper plate 520. And the upper plate 520 can be coupled to the pressing plate 430 in the same shape.

[0235] Thereby, the pressing force provided from the pressing plate 430 where the distributed pressing force is formed can be transmitted to the upper plate 520. The upper plate 520 to which the pressing force is transmitted can face the lower plate 510 to press the object to be molded.

[0236] Therefore, the pressing plate 430 can form a pressing force distributed over its entire surface, which can help form a uniform surface pressure on the molding unit 500.

[0237] In FIGS. 3 to 6, the shape of the pressing plate 430 is formed in a square shape, and the guide rods 440 can be respectively arranged symmetrically on both sides of the pressing rod 420 with the pressing rod 420 as the center. Therefore, two guide rods 440 can be arranged so as to be connected to the pressing plate 430.

[0238] Referring to FIG. 8, the pressing plate 430 has the same square shape, and the guide rods 440 can be arranged symmetrically at the corners of the pressing plate 430 with the pressing rod 420 as the center. Therefore, four guide rods 440 can be arranged so as to be connected to the pressing plate 430.

[0239] In this way, since the four guide rods 440 are symmetrically arranged on the pressing plate 430 with the pressing rod 420 as the center, the degree of dispersion of the pressing force can be further improved.

[0240] Referring to FIG. 9, the pressing plate 430 can be formed in a triangular shape. Three guide rods 440 can be arranged on the triangular pressing plate 430. For example, when the pressing plate 430 is triangular, three guide rods 440 can be arranged on the pressing plate 430 in order to symmetrically arrange the guide rods 440 with the pressing rod 420 as the center.

[0241] In this way, when the pressing plate 430 is triangular, since the three guide rods 440 are symmetrically arranged on the pressing plate 430 with the pressing rod 420 as the center, the degree of dispersion of the pressure can be further improved.

[0242] Referring to FIG. 10, the pressing plate 430 can be formed in a circular shape. Four to eight guide rods 440 can be arranged on the circular pressing plate 430. In this embodiment, the case where eight guide rods 440 are arranged on the pressing plate 430 is shown.

[0243] Specifically, when the pressing plate 430 is circular, four to eight guide rods 440 can be arranged on the pressing plate 430 in order to symmetrically arrange the guide rods 440 around the pressing rod 420.

[0244] Thus, when the pressing plate 430 is circular, four to eight guide rods 440 are symmetrically arranged on the pressing plate 430 around the pressing rod 420, so that the pressure dispersion degree can be further improved.

[0245] FIG. 11 is a flowchart showing a method for manufacturing a cartilage regeneration support using the cartilage regeneration support manufacturing apparatus according to an embodiment of the present invention, FIGS. 12 to 14 are flowcharts showing detailed procedures of the method for manufacturing a cartilage regeneration support in each step of FIG. 11, and FIGS. 15 to 20 are process diagrams showing a method for manufacturing a cartilage regeneration support using the cartilage regeneration support manufacturing apparatus according to an embodiment of the present invention.

[0246] Regarding FIGS. 11 to 20, in order to avoid redundant explanations and facilitate the explanation, reference will be made to FIGS. 3 to 6 for the description.

[0247] In the method for manufacturing a cartilage regeneration support according to an embodiment of the present invention, a cartilage regeneration support can be formed using the cartilage regeneration support manufacturing apparatus 10.

[0248] The manufacturing apparatus 10 for a cartilage regeneration support can include a conveyance unit 300, a molding unit 500, and a pressurization unit 400. The molding unit 500 can include an upper plate 520 and a lower plate 520. An object to be molded can be disposed between the upper plate 520 and the lower plate 510. The manufacturing apparatus 10 for a cartilage regeneration support can provide pressure to the object to be molded to form a cartilage regeneration support with improved pattern uniformity on one or both sides.

[0249] Hereinafter, the present invention will be described in more detail with reference to examples.

[0250] Example Example 1. Fabrication and uniformity measurement of a PLGA large-area sheet (single-sided pattern) A cartilage regeneration support was manufactured using the manufacturing apparatus shown in FIG. 3.

[0251] As shown in FIG. 1, a single-sided PDMS mold (flat) was laid on a plate, and 12 ml of a PLGA solution (including 10 ml of chloroform and 2.5 g of PLGA) prepared by dissolving 25 g of PLGA in 100 ml of chloroform was uniformly applied onto a PUA mold (800 nm) in a size of 12×12 cm. Then, it was turned over so that the PLGA solution was on the bottom and placed on the PDMS mold. Pressure was applied using the manufacturing apparatus shown in FIG. 3, and pattern molding was performed at room temperature for 40 minutes.

[0252] After the pattern molding was completed, the solution was placed with the solution side up on a hot plate at 70° C. to evaporate the solvent (about 1 hour). The solidified PLGA sheet was carefully separated from the PUA mold. The separated PLGA large-area support was immersed in 70% ethanol for about 10 seconds and then washed with purified water. After the washed support was dried for 8 hours or more, it was cut into a size that matched the dimensions. The above process was repeated 4 more times to produce a total of 5 PLGA large-area sheets (FIG. 21).

[0253] The thicknesses of the five prepared large - area PLGA sheets were randomly measured at five points, and the average value of each sample and the overall average value of the measurement data were recorded (Figure 22).

[0254] Example 2. Preparation of a large - area PLGA sheet (double - sided pattern) A support for cartilage regeneration was manufactured using the manufacturing apparatus shown in Figure 3.

[0255] As shown in Figure 1, a double - sided PDMS mold (800 nm) was laid on a plate, and 12 ml of a PLGA solution prepared by dissolving 25 g of PLGA in 100 ml of chloroform (including 10 ml of chloroform and 2.5 g of PLGA) was uniformly applied onto a PUA mold (800 nm) in a size of 12×12 cm. Then, it was turned over so that the PLGA solution was on the bottom and placed on the PDMS mold. Pressure was applied using the manufacturing apparatus shown in Figure 3, and pattern forming was continued at 50 °C for 60 minutes.

[0256] After pattern forming was completed, it was placed on a 70 °C hot plate without separating the upper and lower molds, and dried for 5 hours or more while pressing with a steel plate of about 1.2 kg to prevent the mold from separating. The solidified PLGA was carefully separated from the PDMS and PUA molds. The separated large - area PLGA support was immersed in 70% ethanol for about 10 seconds and then washed three times with purified water. After drying the washed support with air blowing for about 30 minutes, it was cut into a size that matched the dimensions. The above process was repeated four more times to produce a total of five large - area PLGA sheets.

[0257] Example 3. Measurement of the pattern between valleys and mountains of a large - area PLGA sheet by FE - SEM photography For the sheets of Example 1 and 2, FE - SEM photography was performed under the following conditions to measure the distance between valleys and mountains of the nanopattern and the uniformity of the pattern. - Resolution: 0.6 nm - Magnification: X20~2,000,000 - EDS detector (ATW2, 127 eV, 50 mm2 ) As a result, the distance between the peaks and valleys of each pattern of the large-area sheets in Examples 1 and 2 was 790 nm each, and the ratio of peaks to valleys was maintained at 1:1 (FIG. 23). Also, the deviation between five random points of the peaks and five random points of the valleys of the nanopatterns was less than 10 nm, and there was substantially no difference.

Explanation of Signs

[0258] 10: Manufacturing apparatus for cartilage regeneration support 100: Pedestal 110: Pedestal body 120: Table 200: Frame unit 210: Frame body 212: First through-hole 215: Second through-hole 213: First cylinder guide 216: Second cylinder guide 220: Frame support part 300: Conveying unit 310: Conveying rail 320: Carrier 322: Sliding part 328: Fixing surface 330: Conveying drive part 400: Pressing unit 410: Pressing unit body 420: Pressing rod 430: Pressing plate 432: Lower surface of pressing plate 437: Upper surface of pressing plate 439: Fixing part 440: Guide rod 450: Gimbal part 470: Pressure sensor 500: Molding unit 510: Lower plate 512: Lower surface of lower plate 517: Upper surface of lower plate 520: Upper plate 522: Pressing surface of upper plate 527: Coupling surface of upper plate 550: Pressure distribution part 600: Input part 700: Display part 800: Lower mold 810: Second pattern surface 860: Second support surface 900: Upper mold 910: First pattern surface 960: First support surface 1000: Regeneration support 1000a: Biocompatible polymer solution 1000b: Semi-cured product 1010: First pattern 1015: First surface 1020: Second pattern 1025: Second surface 1050: Pattern support part 1051: First pattern surface 1052: Second pattern surface 1100: First mold 1200: Second mold SA: Peripheral area LA: Load area PA: Molding area

Claims

1. It is made of a biocompatible polymer, A pattern for cartilage regeneration is formed on one or both sides, the pattern consists of repeating peaks and valleys; The pattern is a scaffold 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 is the height at P2, H ｎ means the difference in height between the peaks and valleys of a normal pattern.)

2. The support for cartilage regeneration according to claim 1 , wherein P1 and P2 are both points located on a peak or both points located on a valley.

3. The scaffold for cartilage regeneration according to claim 1 , wherein the area satisfying the uniformity of the mathematical formula 1 is 99% or more of the total area.

4. The support for cartilage regeneration according to claim 1, which has a thickness of 30 to 100 μm.

5. The 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. 2. The support for cartilage regeneration according to claim 1, wherein the biocompatible polymer is polylactide-co-glycolide comprising 65 to 85 mol % of lactide and 15 to 35 mol % of glycolide.

7. The support for cartilage regeneration according to claim 1 , wherein the pattern is linear or curved, with the peaks and valleys being repeated side by side.

8. The cartilage regeneration support according to claim 1, wherein one or both sides are coated with any one selected from the group consisting of collagen, growth factors, stem cells, exosomes and therapeutic drugs.

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

10. A step of applying a polymer solution containing a biocompatible polymer onto a polyurethane acrylate mold to prepare a sheet-shaped semi-cured product; applying pressure to the semi-cured material using a polydimethylsiloxane mold to produce a patterned semi-cured material; The method for producing a support for cartilage regeneration according to any one of claims 1 to 9, further comprising a step of drying the patterned semi-hardened material.

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

12. The method for producing a support for cartilage regeneration according to claim 10, wherein said polyurethane acrylate mold or said polydimethylsiloxane mold has projections and recesses for forming said pattern.

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

14. The 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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