Support for cartilage regeneration and method for producing same

Abstract

The present invention relates to a support for cartilage regeneration and a method for preparing the same, and more particularly, to a support for cartilage regeneration and a method for preparing the same, and more particularly, to a support for cartilage regeneration and a method for preparing the same, which have excellent uniformity in thickness of a biocompatible polymer sheet and uniformity in pattern formed on the sheet even when large-area production is performed. The support for cartilage regeneration has excellent cartilage regeneration effect and adhesion to an affected part; and a method for producing the support for cartilage regeneration.

Description

Technical Field

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

[0002] Cartilage is a bone tissue composed of chondrocytes and the cartilage matrix surrounding them. Chondrocytes function to synthesize and secrete the cartilage matrix inside the cartilage. The cartilage matrix gives cartilage elasticity. Different from other tissues, cartilage is not distributed with blood vessels or nerves, so once cartilage is damaged, it is difficult to regenerate. Thus, due to the insufficient self-repair ability of cartilage, surgical treatments such as microfracture are required for treating cartilage damage.

[0003] Microfracture is a surgery for regenerating damaged cartilage. It is a technique that utilizes the principle of forming microfractures on the bone exposed due to cartilage damage. When the subchondral bone is damaged, bone marrow components including bone marrow stem cells leak, and these cells differentiate to form cartilage.

[0004] Most of the cartilage generated by microfracture is fibrocartilage rather than hyaline cartilage. Fibrocartilage is rich in type I collagen and has a low content of proteoglycans, resulting in reduced wear resistance. Therefore, when the damaged cartilage tissue regenerates into fibrocartilage, the symptoms improve by 60 to 70% around 2 years after the operation, but structural disintegration may occur later and the symptoms may worsen. Also, it is known that the larger the defect site, the more severe the symptom deterioration. The microfracture treatment method has the disadvantages of treatment limitations for extensive cartilage defects and the regeneration of fibrocartilage with weak mechanical properties. Therefore, together with microfracture treatment, a support for cartilage regeneration needs to be transplanted to the cartilage defect site to promote cartilage regeneration and improve maturity during the cartilage regeneration process.

[0005] Only when the thickness and pattern are uniform can the support for cartilage regeneration enable chondrocytes to grow densely and regularly. However, there are limitations in making the thickness and pattern of the support for cartilage regeneration uniform in the existing methods. In particular, when preparing the support for cartilage regeneration with an area above a specified area, the non-uniformity of the thickness and pattern increases.

[0006] Prior Art Documents

[0007] Patent Documents

[0008] (Patent Document 1) Korean Patent Publication No. 10-2023-0026083 Summary of the Invention

[0009] Technical Problem

[0010] An object of the present invention is to provide a support for cartilage regeneration in which the thickness and pattern are uniformly formed and a method for preparing the same.

[0011] An object of the present invention is to provide a cartilage regeneration support capable of adhering to a cartilage defect site with high adhesion and a method for producing the same.

[0012] Solution to the problem

[0013] 1. Regarding the cartilage regeneration support, it is formed of a biocompatible polymer, and a pattern for cartilage regeneration is formed on one side or both sides. The pattern is formed by repeated ridges and grooves, and the area of the pattern satisfying the uniformity (U) of the following Mathematical Formula 1 is 95% or more of the total area.

[0014] Mathematical Formula 1

[0015] U = |H P1 -H P2 | ≤ 0.1H n

[0016] (In the mathematical formula, H P1 means the height in P1, H P2 means the height in P2, H n means the height difference between the above-mentioned ridges and the above-mentioned grooves of the normal pattern)

[0017] 2. Regarding the cartilage regeneration support, in the above 1, the above P1 and P2 are locations where both are located on the ridge or both are located in the groove.

[0018] 3. Regarding the cartilage regeneration support, in the above 1, the area satisfying the uniformity of Mathematical Formula 1 is 99% or more of the total area.

[0019] 4. Regarding the cartilage regeneration support, in the above 1, the thickness is 30 to 100 μm.

[0020] 5. Regarding the cartilage regeneration support, in the above 1, the biocompatible polymer is one selected from the group consisting of polycaprolactone, poly(lactic-co-glycolic acid), polyethylene glycol, poly(ethylene oxide), polylactic acid, and polyglycolic acid.

[0021] 6. Regarding the cartilage regeneration support, in the above 1, the biocompatible polymer is a poly(lactic-co-glycolic acid) having 65 to 85 mol% of lactide and 15 to 35 mol% of glycolide.

[0022] 7. Regarding the cartilage regeneration support, in the above 1, the pattern has a linear or curved shape in which ridges and grooves are repeated side by side.

[0023] 8. Regarding the cartilage regeneration support, in the above 1, one side or both sides are coated with one selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs.

[0024] 9. Regarding the support for cartilage regeneration, in the above 1, fibrin is coated on the edge.

[0025] 10. Regarding the method for preparing a support for cartilage regeneration, the support for cartilage regeneration described above is described in any one of the above 1 to 9. The method for preparing the support for cartilage regeneration includes: a step of coating a polymer solution including a biocompatible polymer on a polyurethane acrylate mold to prepare a sheet-like semi-cured product; a step of applying pressure to the semi-cured product using a polydimethylsiloxane mold to prepare a patterned semi-cured product; and a step of drying the patterned semi-cured product.

[0026] 11. Regarding the method for preparing a support for cartilage regeneration, in the above 10, the patterned semi-cured product is prepared by applying pressure using an upper plate and a lower plate after placing the semi-cured product between the polyurethane acrylate mold and the polydimethylsiloxane mold.

[0027] 12. Regarding the method for preparing a support for cartilage regeneration, in the above 10, the polyurethane acrylate mold or the polydimethylsiloxane mold is formed with unevenness for forming a pattern.

[0028] 13. Regarding the method for preparing a support for cartilage regeneration, in the above 11, the upper plate has a pressing rod and a guide rod.

[0029] 14. Regarding the method for preparing a support for cartilage regeneration, in the above 10, the pressure is 0.40 Pa to 0.70 Pa.

[0030] Effects of the Invention

[0031] The cartilage regeneration effect of the support for cartilage regeneration of the present invention is excellent.

[0032] The adhesion of the support for cartilage regeneration of the present invention is excellent.

[0033] The workability of the support for cartilage regeneration of the present invention is excellent. Brief Description of the Drawings

[0034] Figure 1 It is a conceptual diagram of the preparation process of the support for cartilage regeneration of the present invention.

[0035] Figure 2 Briefly shows the method for measuring the uniformity (U) of Mathematical Formula 1.

[0036] Figure 3 It is a perspective view of a device for preparing a support for cartilage regeneration according to an embodiment of the present invention.

[0037] Figure 4 It is a front view of a device for preparing a support for cartilage regeneration according to an embodiment of the present invention.

[0038] Figure 5 The top view of the support preparation device for cartilage regeneration according to an embodiment of the present invention.

[0039] Figure 6 Is the sectional view along Figure 5 A1 - A2 of

[0040] Figure 7 The block diagram showing the support preparation device for cartilage regeneration according to an embodiment of the present invention.

[0041] Figure 8 The top view showing the shape of the pressure plate of the pressure unit according to an embodiment of the present invention.

[0042] Figure 9 The top view showing another shape of the pressure plate of the pressure unit according to an embodiment of the present invention.

[0043] Figure 10 The top view showing yet another shape of the pressure plate of the pressure unit according to an embodiment of the present invention.

[0044] Figure 11 The flowchart showing the preparation method of the support for cartilage regeneration using the support preparation device for cartilage regeneration according to an embodiment of the present invention.

[0045] Figures 12 to 14 Is according to Figure 11 The flowchart of the detailed preparation method of the support for cartilage regeneration for each step of

[0046] Figure 15 to Figure 20 The process diagram showing the preparation method of the support for cartilage regeneration using the support preparation device for cartilage regeneration according to an embodiment of the present invention.

[0047] Figure 21 The photo of the PLGA large - area sheet of the embodiment of the present invention.

[0048] Figure 22 The photo for measuring the thickness of the PLGA large - area sheet of the embodiment of the present invention.

[0049] Figure 23 Is the photo for measuring the pattern between the groove part and the ridge part of the PLGA large - area sheet of the embodiment of the present invention.

[0050] Explanation of reference numerals

[0051] 10: Support preparation device for cartilage regeneration 100: Bracket

[0052] 110: Bracket body 120: Workbench

[0053] 200: Frame unit 210: Frame body

[0054] 212: First through-hole 215: Second through-hole

[0055] 213: First cylinder guide 216: Second cylinder guide

[0056] 220: Frame support part 300: Transfer unit

[0057] 310: Transfer guide rail 320: Carrier

[0058] 322: Sliding part 328: Placing surface

[0059] 330: Transfer driving part 400: Pressing unit

[0060] 410: Pressing unit body 420: Pressing rod

[0061] 430: Pressing plate 432: Lower surface of pressing plate

[0062] 437: Upper surface of pressing plate 439: Placing part

[0063] 440: Guide rod 450: Universal joint head

[0064] 470: Pressure sensor 500: Molding unit

[0065] 510: Lower plate 512: Lower surface of lower plate

[0066] 517: Upper surface of lower plate 520: Upper plate

[0067] 522: Pressing surface of upper plate 527: Joint surface of upper plate

[0068] 550: Pressure dispersion part 600: Input part

[0069] 700: Display part 800: Lower mold

[0070] 810: Second pattern surface 860: Second support surface

[0071] 900: Upper mold 910: First pattern surface

[0072] 960: First support surface 1000: Regenerated support

[0073] 1000a: Biocompatible polymer solution 1000b: Semi-cured product

[0074] 1010: First pattern 1015: First surface

[0075] 1020: Second pattern 1025: Second surface

[0076] 1050: Pattern support part 1051: First pattern surface

[0077] 1052: Second pattern surface 1100: First mold

[0078] 1200: Second mold SA: Peripheral area

[0079] LA: Loading area PA: Molding area Detailed implementation manner

[0080] The present invention provides a support body for cartilage regeneration and a preparation method thereof.

[0081] The present invention provides a support body preparation device for cartilage regeneration, which is prepared to include a specified mold and structure. Even in large-scale production, the uniformity of the thickness of the biocompatible polymer sheet and the uniformity of the pattern formed on the sheet are excellent, and the cartilage regeneration effect and the adhesion to the affected area are excellent. A support body for cartilage regeneration and a preparation method thereof.

[0082] The present invention provides a support body for cartilage regeneration, which is formed of a biocompatible polymer, and patterns for chondrocyte growth are formed on one side or both sides. The patterns are formed by repeated ridges and grooves, and the area of the pattern satisfying the uniformity (U) of the following Mathematical Formula 1 is 95% or more of the total area.

[0083] Mathematical Formula 1

[0084] U = |H P1 - H P2 | ≤ 0.1H n

[0085] (In the above mathematical formula, H P1 means the height in P1, H P2 means the height in P2, H n means the height difference between the above-mentioned ridges and the above-mentioned grooves of the normal pattern.)

[0086] Although the support body for cartilage regeneration of the present invention is thin, it has high uniformity and appropriate elongation and tensile strength as a support body for cartilage regeneration, and its cartilage regeneration effect is excellent and its adhesion to the affected area is excellent.

[0087] The support body for cartilage regeneration of the present invention is formed of a biocompatible polymer.

[0088] Biocompatible polymers are not limited to being formed from specific raw materials. For example, it may be 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).

[0089] When the support for cartilage regeneration is formed from polylactide-co-glycolide or polycaprolactone, it is preferred in terms of uniformity and physical properties (elongation rate, tensile strength, etc.). To achieve the object of the present invention, more preferably, it is formed from PLGA comprising lactide (LA) monomer and glycolide (GA) monomer in a molar ratio of 65 to 85 to 35 to 15.

[0090] Patterns for chondrocyte growth are formed on one or both sides of the biocompatible polymer of the present invention.

[0091] When the support for cartilage regeneration is attached to the affected area, chondrocytes present around the support grow along the groove portion of the pattern, inducing the regeneration of damaged cartilage.

[0092] The pattern can be formed on one or both sides. To facilitate the distinction between the upper surface / lower surface of the support for cartilage regeneration, the pattern can be formed only on the upper surface or the lower surface. Also, when the size of the support for cartilage regeneration is such, the pattern can be formed on both sides, avoiding the distinction between the upper surface / lower surface.

[0093] As long as the pattern is a shape in which ridges and grooves are repeated, it is not limited to a specific shape. For example, the pattern can be a straight or curved shape in which ridges and grooves are arranged side by side. The shape of the pattern can be formed by a straight line parallel to one corner of the support for cartilage regeneration, an oblique line forming a specified angle with one corner, a wavy curve, etc.

[0094] The ridge means a relatively protruding part, and the groove means a relatively recessed part existing between the ridges. Chondrocytes grow along the groove between the ridges.

[0095] *50 The width between the ridges 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, 600 to 700 nm, etc.

[0096] The width between the groove portions can also be designed to be the same as the width between the ridge portions.

[0097] The height difference between the ridge portion and the groove portion (the height of the ridge portion when based on the groove portion) 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, 600 to 700 nm, etc.

[0098] The distance between the ridge portions of the pattern, the distance between the groove portions, and the height difference between the ridge portion and the groove portion can be the same or different. When they are different, the differences can be respectively 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.

[0099] For example, the distance between the ridge portions, the distance between the groove portions, and the height difference between the ridge portion and the groove portion can be 800 nm, 700 nm, or 600 nm, etc., and can be the same. Also, the distance between the ridge portions and the distance between the groove portions can be 800 nm, and the height difference between the ridge portion and the groove portion can be 750 nm or 850 nm. And, the distance between the ridge portions and the distance between the groove portions can be 700 nm, and the height difference between the ridge portion and the groove portion can be 650 nm or 750 nm.

[0100] The distance between the ridge portions of the pattern, the distance between the groove portions, and the height difference between the ridge portion and the groove portion can be changed by adjusting the size and interval of the pattern formed on the mold used in preparing the support for cartilage regeneration.

[0101] In the pattern, the area with the uniformity (U) satisfying the following mathematical formula 1 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.

[0102] Mathematical formula 1

[0103] U = |H P1 - H P2 | ≤ 0.1H n

[0104] In the above mathematical formula, H P1 means the height in P1, H P2 means the height in P2, H n means the height difference between the ridge portion and the groove portion of the normal pattern.

[0105] Both P1 and P2 are any locations on the ridge portion of the pattern or both are any locations on the groove portion of the pattern.

[0106] For example, P1 and P2 can be locations on the same ridge. P1 can be a location on one ridge, and P2 can be a ridge adjacent to that ridge, that is, a location on another ridge that exists across a groove located on the left or right of that ridge. Also, P1 can be a location on one ridge, and P2 can be a ridge separated from that ridge, that is, a location on another ridge that exists across multiple grooves located on the left or right of that ridge.

[0107] H P1 is the height in P1. The height in P1 means the height from the groove to a location on the ridge, that is, the height of P1. When the ridge is formed at a desired height, H P1 is the same as the height of the pattern formed on the mold, and is the same as the height difference between the ridges and grooves of the normal pattern, that is, H n is the same. When the pattern formation is defective, H P1 is different from the height of the pattern formed on the mold.

[0108] H P2 refers to the height in P2. It is the same as H P1 is the same.

[0109] In the support for cartilage regeneration of the present invention, the height difference between P1 and P2 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 height difference between the ridges and grooves of the normal pattern (H n ).

[0110] When the thickness and pattern uniformity of the support for cartilage regeneration are excellent, along the uniform pattern, smooth cell proliferation of chondrocytes is achieved, presenting an excellent effect for cartilage regeneration. When there are uneven patterns or partially damaged patterns, cell proliferation in the damaged part of the pattern may be interrupted.

[0111] When P1 and P2 are locations on the same ridge, if the pattern uniformity is measured, the height differences between P3 and P4, which are arbitrary locations on the groove of the pattern, can be selectively additionally considered.

[0112] P3 and P4 can be locations on the same groove. P3 can be a location on one groove, and P4 can be a groove adjacent to that groove, that is, a location on another groove that exists across a ridge located on the left or right of that groove. Also, P3 can be a location on one groove, and P4 can be a groove separated from that groove, that is, a location on another groove that exists across multiple ridges located on the left or right of that groove.

[0113] When P1 and P2 are arbitrary locations on the ridge, and P3 and P4 are arbitrary locations on the groove, U is satisfied 1= |H P1 -H P2 | ≤ 0.1H n and U 2 = |H P3 -H P4 | ≤ 0.1H n (H P3 means the height in P3, H P4 means the height in P4, H n means that the area of the height difference between the ridges and grooves of the normal pattern) can 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.

[0114] The thickness of the support for cartilage regeneration can be 30 to 100 μm, preferably 40 to 70 μm, more preferably 50 to 60 μm. When 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. When the thickness is greater than 100 μm, the adhesion decreases, and it is difficult for the support to adhere to the cartilage within a sufficient time required for cartilage regeneration.

[0115] The tensile strength of the support for cartilage regeneration can be 3 to 8 MPa, preferably 4 to 6 MPa. The elongation rate of the support for cartilage regeneration can be 4 to 10%, preferably 5 to 7%. When the tensile strength is less than 3 MPa or the elongation rate is greater than 10%, it is likely to deform and difficult to handle, and the patient may feel discomfort after surgery. When the tensile strength is greater than 8 MPa or the elongation rate is less than 4%, there may be problems such as being easily broken, insufficient flexibility, and inability to properly adhere to the cartilage.

[0116] The adhesion strength of the support for cartilage regeneration can be 0.2 to 0.5 N / cm 2 , preferably 0.3 to 0.4 N / cm 2 .

[0117] One or more selected from the group consisting of collagen, growth factors, stem cells, exosomes, and therapeutic drugs can be coated on one side or both sides of the support for cartilage regeneration. The above factors coated on the support can promote cell growth to increase the cartilage regeneration rate.

[0118] Fibrin can be coated on the edge of the support for cartilage regeneration. The fibrin coated on the edge can form a fibrous thrombus and act as a bridge for cell migration, thereby making the cell migration and proliferation at the cartilage injury site smooth and increasing the cartilage regeneration rate.

[0119] The support for cartilage regeneration can be prepared by a method including the following steps: coating a polymer solution including a biocompatible polymer and an organic solvent on a polyurethane acrylate (PUA) mold to prepare a sheet-like semi-cured product; applying pressure to the semi-cured product using a polydimethylsiloxane (PDMS) mold to prepare a patterned semi-cured product; and drying the patterned semi-cured product.

[0120] The support for cartilage regeneration can be prepared by a method including the following steps: coating a polymer solution including a biocompatible polymer and an organic solvent on a polyurethane acrylate (PUA) mold to prepare a sheet-like semi-cured product; after placing the semi-cured product between a polyurethane acrylate (PUA) mold and a polydimethylsiloxane (PDMS) mold, applying pressure using an upper plate and a lower plate to prepare a patterned semi-cured product; and drying the patterned semi-cured product.

[0121] In the polyurethane acrylate (PUA) mold and / or the polydimethylsiloxane (PDMS) mold, unevenness for forming a pattern is formed on one side and / or both sides of the support.

[0122] More specifically, the support for cartilage regeneration can be prepared by a method including the following steps: a semi-cured product forming step S100, a semi-cured product fixing step S200, a transfer step S300, a pressing step S400, a drying step S500, and a separation step S600.

[0123] Refer to Figure 12 And FIG. 15(A), the semi-cured product forming step S100 may include a step S110 of arranging the upper mold 900 on the surface of the base. The above base can be the ground, can be a structure with a flat surface, or can be the lower plate 510. When the surface of the base is the lower plate 510, the lower plate 510 can be arranged on the loading area LA. In this embodiment, the case where the illustrated base is the lower plate 510 will be described.

[0124] The upper mold 900 is a polyurethane acrylate (PUA) mold.

[0125] The upper mold 900 may include a first pattern surface 910 formed with a pattern and a first support surface 960 disposed on the opposite surface of the first pattern surface 910. The first support surface 960 can be placed on the surface of the above base.

[0126] The first pattern surface 910 may include a pattern having a prescribed shape. The pattern is not limited to a specific shape as long as it is a shape in which ridges and grooves are repeated. For example, the pattern may be a straight or curved shape in which ridges and grooves are arranged side by side repeatedly. The shape of the pattern may be a straight line parallel to one corner of the support for cartilage regeneration, an oblique line forming a prescribed angle with one corner, a wavy curve, etc.

[0127] The width between ridges and ridges is, 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., and can be designed diversely according to the pattern of the support for cartilage regeneration to be prepared.

[0128] The width between grooves and grooves can also be designed to be the same as the width between ridges and ridges.

[0129] The height difference between a ridge and a groove (the height of the ridge when the groove is used as a reference) is 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., and can be designed diversely according to the pattern of the support for cartilage regeneration to be prepared.

[0130] The distance between ridges and ridges, the distance between grooves and grooves, and the height difference between a ridge and a groove of 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.

[0131] For example, the distance between ridges and ridges, the distance between grooves and grooves, and the height difference between a ridge and a groove may be 800 nm, 700 nm, or 600 nm, etc., respectively, and may be the same. Also, the distance between ridges and ridges and the distance between grooves and grooves may be 800 nm, and the height difference between a ridge and a groove may be 750 nm or 850 nm. Also, the distance between ridges and ridges and the distance between grooves and grooves may be 700 nm, and the height difference between a ridge and a groove may be 650 nm or 750 nm.

[0132] The size and interval of the pattern formed on the mold can be adjusted to change the size and interval of the pattern of the support for cartilage regeneration to be prepared.

[0133] Refer to Figure 12As shown in FIG. 15(B), step S100 of forming the semi-cured product 1000b may include step S120 of coating the first pattern surface 910 of the upper mold 900 with the biocompatible polymer solution 1000a. By coating the biocompatible polymer solution 1000a on the PUA mold (upper mold, 900), a sheet-like semi-cured product 1000b can be formed.

[0134] The biocompatible polymer solution can be prepared by mixing a biocompatible polymer and an organic solvent. As the organic solvent, for example, halogenated methane solvents such as chloroform or dichloromethane can be used.

[0135] The suitable concentration of the biocompatible polymer solution may vary depending on the type of the biocompatible polymer. For example, the concentration of the biocompatible polymer in the biocompatible polymer solution can be 15% (w / w) to 24% (w / w). When the biocompatible polymer is PLGA, the concentration can be 15% (w / w) to 21% (w / w), and when the biocompatible polymer is PCL, the concentration can be 18% (w / w) to 24% (w / w).

[0136] During the process of coating the biocompatible polymer solution 1000a, at room temperature, a part of the solvent evaporates to form a sheet-like semi-cured product 1000b. Thus, even if the upper mold 900 is turned upside down, the semi-cured product does not flow.

[0137] In this way, the upper mold 900 with the semi-cured product 1000b disposed on the first pattern surface 910 is referred to as the first mold 1100.

[0138] Since the first mold 1100 has the semi-cured product 1000b disposed on the upper mold 900, it is necessary to turn the first mold 1100 upside down later to bring it into contact with the lower mold 800.

[0139] Therefore, in order to bring the surface of the semi-cured product 1000b exposed by turning the first mold 1100 upside down into contact with the lower mold 800, a biocompatible polymer with a high viscosity can be used or a solvent with a high volatility can be used to quickly evaporate the solvent, so as to increase the viscosity of the semi-cured product 1000b and prevent it from flowing.

[0140] Refer to Figure 11 , the method for preparing the support for cartilage regeneration according to the present invention may include step S200 of fixing the semi-cured product 1000b. The fixing of the semi-cured product 1000b is a step of bringing the semi-cured product 1000b exposed by turning the first mold 1100 upside down 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.

[0141] The lower mold 800 is a polydimethylsiloxane (PDMS) mold.

[0142] Referring to Figure 13 Figure 13 and FIG. 16(A), step S200 of fixing the semi-cured material 1000b may include step S210 of disposing the carrier 320 on the loading area LA.

[0143] The lower plate 510 may be disposed on the carrier 320. For example, the lower surface 512 of the lower plate may be placed on the carrier placement surface 328. Thus, on the loading area LA, the lower plate 510 may be disposed such that the upper surface 517 of the lower plate is exposed.

[0144] Referring to Figure 13 Figure 13 and FIG. 16(B), step S200 of fixing the semi-cured material 1000b may include step S220 of disposing the lower mold 800 on the lower plate 510. For example, on the loading area LA, the lower mold 800 may be disposed on the upper surface 517 of the lower plate.

[0145] The lower mold 800 may include a non-patterned flat surface 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. Thus, on the loading area LA, when the lower mold 800 is disposed on the lower plate 510, the flat surface may be exposed to the outside. The lower mold 800 having a non-patterned flat surface is used for preparing a support for single-sided nano-patterned cartilage regeneration.

[0146] The lower mold 800 may include a second pattern surface 810 and a second support surface 860 formed on the opposite surface of the second pattern surface 810. The second pattern surface 810 may be a non-patterned flat surface or a surface formed with a pattern. In the case of the non-patterned flat surface, it is used for preparing a support for single-sided patterned cartilage regeneration, and in the case of the surface formed with a pattern, it is used for preparing a support for double-sided patterned cartilage regeneration. The second support surface 860 may be placed on the upper surface 517 of the lower plate. Thus, on the loading area LA, when the lower mold 800 is disposed on the lower plate 510, the second pattern surface 810 may be exposed to the outside.

[0147] Referring to Figure 13 Figure 13 and FIG. 16(C), step S200 of fixing the semi-cured material 1000b may include step S230 of bringing the first mold 1100 into contact with the lower mold 800. For example, the first mold 1100 may be disposed on the second pattern surface 810 in such a manner that the semi-cured material 1000b is in contact therewith to fix the semi-cured material.

[0148] Step S200 of fixing the semi-cured material 1000b may expose the first support surface 960 of the upper mold 900 to the outside on the loading area LA.

[0149] Referring to Figure 11 and Figure 17, The method for preparing a support for cartilage regeneration according to an embodiment of the present invention may include a transfer step S300 of transferring the second mold 1200.

[0150] In the transfer step S300, the second mold 1200 disposed on the loading area LA may be moved to the molding area PA.

[0151] Above the molding area PA, a pressure plate 430 of the pressing unit 400 may be disposed. The pressure plate 430 may be coupled with an upper plate 520. Accordingly, the second mold 1200 may be disposed below the upper plate 520.

[0152] For example, the pressure plate 430 may include a lower pressure plate surface 432 and an upper pressure plate surface 437. The lower pressure plate surface 432 may be coupled with the upper plate 520.

[0153] The upper plate 520 may include an upper plate pressing surface 522 and an upper plate coupling surface 527. The upper plate coupling surface 527 may be coupled with the lower pressure plate surface 432. And, a pressure dispersion part 550 may be bonded to the upper plate pressing surface 522.

[0154] Below the molding area PA, a transfer unit 300 for moving the second mold 1200 to move the second mold 1200 and a lower plate 510 disposed on the transfer unit 300 may be disposed.

[0155] For example, the transfer unit 300 may include a transfer guide rail 310 and a carrier 320. The lower plate 510 may be disposed on the carrier 320. The second mold 1200 may be disposed on the lower plate 510. Accordingly, the second mold 1200 may be disposed in the molding area PA.

[0156] In addition, the transfer unit 300 may further include a transfer driving part 330 for moving the carrier 320. By driving the transfer driving part 330, the carrier 320 may be moved from the loading area LA to the molding area PA.

[0157] Accordingly, in the molding area PA, the second mold 1200 may be disposed in the lower direction of the pressure dispersion part 550. For example, in the transfer step S300, on the molding area PA, the pressure dispersion part 550 and a first support surface 960 as an exposed surface of the second mold 1200 may be disposed facing each other.

[0158] Refer to Figure 11 , The method for preparing a support for cartilage regeneration according to an embodiment of the present invention may include a pressing step S400 of the semi-cured product 1000b that is press-fixed.

[0159] For example, refer to Figure 14 and FIG. 18(A), the pressing step S400 may be performed in the molding area PA.

[0160] The pressing step S400 of the pressure-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 may 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 part 550 may be brought into contact with the first support surface 960.

[0161] In the step S410 of bringing the upper plate 520 into contact with the second mold 1200, it may include a step of starting the pressing unit 400. For example, the pressing unit 400 may start an actuator disposed in the pressing unit body 410. The above actuator may be connected to a pressing rod 420. The pressing rod 420 may move in the direction of the pressing plate 430. The pressing rod 420 may be placed in a placement part 439 disposed on one surface of the pressing plate 430.

[0162] The pressing rod 420 may move in the up and down directions. When moving in the lower direction of the pressing rod 420, the upper plate 520 combined with the pressing plate 430 may move in the lower direction. Therefore, the upper plate 520 may move in the direction of the lower plate 510.

[0163] The upper plate 520 may be moved so that the upper plate pressing surface 522 comes into contact with the second mold 1200 disposed on the lower plate 510. More specifically, the pressure dispersion part 550 may be brought into contact with the first support surface 960 of the upper mold 900 exposed in the second mold 1200.

[0164] In the step S410 of bringing the upper plate 520 into contact with the second mold 1200, there may be a situation where the thickness of a part of the second mold 1200 is different from that of another part.

[0165] For example, during the coating process of the biocompatible polymer solution 1000a, the above thickness difference may occur because the biocompatible polymer solution 1000a is unevenly configured. Or, the above thickness difference may also occur in the formed thickness of the upper mold 900 and the lower mold 800.

[0166] When the above thickness difference occurs, the upper plate 520 may tilt, resulting in a situation where the entire surface (Whole surface) of the pressure dispersion part 550 and the entire surface (Whole surface) of the first support surface 960 cannot be in surface contact.

[0167] Refer to Figure 14 And Fig. 18(B), the pressing step S400 may include a step S420 of adjusting the tilt of the upper plate 520.

[0168] In step S420 of adjusting the inclination, the upper plate 520 can be brought into surface contact with the fixed semi-cured material 1200. For example, in step S420 of adjusting the inclination of the upper plate 520, the whole surface of the pressure dispersion part 550 can be brought into surface contact with the whole surface of the first support surface 960.

[0169] After bringing the two above-mentioned structural surfaces into contact, the step of adjusting the level of the upper plate 520 can be implemented. That is, the upper plate 520 can be rotated (the inclination is adjusted).

[0170] The inclination of the upper plate 520 can be adjusted by the universal joint part 450. The universal joint part 450 can be arranged on the upper surface of the pressure plate 430. For example, the universal joint part 450 can be arranged between the guide rod 440 of the pressing unit 400 and the pressure plate 430. And the universal joint part 450 can be arranged between the placement part 439 and the pressure plate 430.

[0171] When the inclination of the upper plate 520 is non-horizontal, the universal joint part 450 can rotate the upper plate 520 to adjust the level of the upper plate 520.

[0172] Therefore, the universal joint part 450 can provide the load of the upper plate 520 to the above-mentioned thickness difference occurrence area of the second mold 1200. For example, in order to adjust the level, the universal joint part 450 can rotate (the inclination) the upper plate 520 to provide the load to the above-mentioned thickness difference occurrence area. Among them, the upper plate 520 is combined with the pressure plate 430, so the load of the upper plate 520 and the pressure plate 430 can be provided to the second mold 1200.

[0173] 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-cured material 1200. Therefore, the load of the upper plate 520 and the pressure plate 430 can press the fixed semi-cured material 1000b in the above-mentioned thickness difference occurrence area.

[0174] When the level of the upper plate 520 is formed, the universal joint part 450 can stop providing the load to the second mold 1200.

[0175] Refer to Figure 14 and Figure 19 , the step S430 of maintaining the pressing force on the pressure plate 430 can be included.

[0176] The step S430 of maintaining the pressing force can be executed 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.

[0177] In the above state, the target pressing force can be maintained in 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 0.45 to 0.65 MPa, can be provided to the pressing plate 430. The pressing force providing time may vary according to the magnitude of the pressing force. For example, it can be provided within a maintaining time of 30 minutes to 50 minutes.

[0178] 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 material 1200.

[0179] Through 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 material 1000b.

[0180] Refer to Figure 11 and Figure 20 , a drying step S500 of drying the semi-cured material 1000b can be included.

[0181] In the drying step S500, the target drying heat can be provided to the second mold 1200 through the lower plate 510. Or, the second mold 1200 can be dried in a drying oven or on a hot plate, and finally the semi-cured material 1000b can be dried.

[0182] When drying the second mold 1200 through the lower plate 510, a heating plate can be provided inside the lower plate 510. The above heating plate can transfer heat energy to the upper surface 517 of the lower plate to dry the second mold 1200. The heat energy transferred to the second mold 1200 can be transferred to the semi-cured material 1000b to dry the semi-cured material 1000b.

[0183] 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 unloaded on the lower plate 510 can be loaded and unloaded from the loading area LA. The second mold 1200 can be loaded and unloaded and loaded into the dryer DO, and the above drying heat can be provided to the second mold 1200.

[0184] Among them, in the drying step S500, heat energy of 15 °C to 45 °C can be provided to the second mold 1200 for 6 hours to 10 hours.

[0185] On the other hand, in the drying step S500, the second mold 1200 can be placed on a hot plate for drying. When using a hot plate, a steel plate of 0.5 Kg to 2 Kg can be stacked 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 heating temperature can be maintained for 4 hours to 8 hours to dry the second mold 1200.

[0186] Among them, the above-mentioned steel plate can prevent the upper mold 900 or the lower mold 800 from separating from the semi-cured material 1000b during the drying process.

[0187] When the upper mold 900 or the lower mold 800 separates during the drying process, the surface pattern of the semi-cured material 1000b may be damaged. Therefore, the process of placing the above-mentioned steel plate on the second mold 1200 for drying can be performed to prevent damage to the surface pattern of the semi-cured material 1000b.

[0188] In this way, the second mold 1200 can be dried, and a cured support 1000 for cartilage regeneration can be formed between the upper mold 900 and the lower mold 800.

[0189] Refer to Figure 11 and Figure 20 , and the step S600 of separating the cartilage regeneration support 1000 from the second mold 1200 can be implemented.

[0190] The cartilage regeneration support 1000 formed between the lower mold 800 and the upper mold 900 that constitutes the second mold 1200 can be separated from the lower mold 800 and the upper mold 900.

[0191] After the separation step S600, the cartilage regeneration support 1000 can be immersed in 70% ethanol for 10 seconds and washed with purified water.

[0192] The method for preparing the cartilage regeneration support of the present invention can be performed using the cartilage regeneration support preparation device 10 described below. The following figure shows the cartilage regeneration support preparation device for detailed description.

[0193] Figure 3 It is a perspective view of the cartilage regeneration support preparation device according to an embodiment of the present invention, Figure 4 It is a front view of the cartilage regeneration support preparation device according to an embodiment of the present invention, Figure 5 It is a top view of the cartilage regeneration support preparation device according to an embodiment of the present invention, Figure 6 It is along Figure 5 The cross-sectional view of A1-A2.

[0194] Refer to Figures 3 to 6The device 10 for preparing a support for cartilage regeneration may include a bracket 100 .

[0195] The carriage 100 may include a carriage body 110 and a workbench 120 .

[0196] The workbench 120 may be formed of a plate having a flat surface. A plurality of structures may be arranged on the workbench 120. The flat surface may provide a stable placement surface for the structure.

[0197] The bracket body 110 may have a plurality of legs. The plurality of legs may be arranged at the corners of the workbench 120. The plurality of legs may be arranged at different set lengths or at the same set length. The plurality of legs with set lengths adjusted may form a flat surface of the workbench 120.

[0198] Furthermore, the plurality of legs can be arranged at a set length corresponding to the working height of the staff. For example, the plurality of legs can be arranged at the working height expected by the staff. The plurality of legs with adjustable height can improve the working efficiency of the staff.

[0199] The apparatus 10 for preparing a support for cartilage regeneration may include a frame unit 200. The frame unit 200 may be disposed on a workbench 120. The frame unit 200 may include a frame support 220 and a frame body 210.

[0200] The frame bracket 220 can support the frame body 210. The frame bracket 220 can be disposed on the upper surface of the workbench 120. The frame bracket 220 can be set on the workbench 120 to fix the frame body 210. The frame bracket 220 and the workbench 120 can be fixed by a combination structure such as a fixing screw, but the fixing mechanism is not limited to the fixing screw. In addition, the frame bracket 220 and the frame body 210 can also be fixed by a similar fixing mechanism.

[0201] The frame body 210 may be disposed on the workbench 120. For example, the frame body 210 may be located on the upper surface of the workbench 120 and supported by the frame bracket 220. The frame body 210 may be configured in a plate shape. Therefore, the frame body 210 may be configured in a direction parallel to the flat surface of the workbench 120.

[0202] The frame body 210 may have a plurality of through holes 212 and 215. The frame body 210 may be provided with cylinder guides 213 and 216 on the plurality of through holes 212 and 215, respectively.

[0203] The plurality of through holes 212 and 215 may include a first through hole 212 and a second through hole 215. The first through hole 212 may be provided with a guide rod 440. The second through hole 215 may be provided with a pressurizing rod 420.

[0204] A plurality of first through holes 212 may be disposed around the second through hole 215. The first through holes 212 can be arranged symmetrically around the second through hole 215.

[0205] In the present embodiment, it is illustrated that two first through holes 212 are symmetrically arranged around the second through hole 215 for explanation. However, the arrangement of the first through holes 212 is not limited thereto, and 3 to 8 first through holes 212 can be symmetrically arranged around the second through hole 215.

[0206] The guide rod 440 can disperse the concentrated pressure provided from the pressing rod 420 in the surface direction of the pressing plate 430. Therefore, the number of the first through holes 212 arranged is related to the number of the guide rods 440, and thus can play a role in forming the dispersed pressure of the pressing plate 430. The pressing plate 430 forming the dispersed pressure can contribute to forming a uniform surface pressure on the molding unit 500.

[0207] The support preparation device 10 for cartilage regeneration may include a transfer unit 300.

[0208] For the sake of convenience of explanation, in the workbench 120, the area composed of the frame bracket 220 and the frame body 210 is defined as the molding area PA, and the area other than the molding area PA is defined as the peripheral area SA. The area where the transfer unit 300 is arranged in the peripheral area SA is defined as the loading area LA.

[0209] The transfer unit 300 may include a transfer guide rail 310, a carrier 320, and a transfer driving unit 330.

[0210] The transfer guide rail 310 may be arranged on the upper surface of the workbench 120. The transfer guide rail 310 may be arranged from the loading area LA via the molding area PA. The transfer guide rail 310 is a pair of guide rails arranged in the direction from the loading area LA to the molding area PA, and can form a guide rail portion. At least one of the above guide rail portions may be arranged. For example, when there are a plurality of guide rail portions formed by the transfer guide rail 310 in the direction from the loading area LA to the molding area PA, a plurality of working windows may be formed in the loading area LA.

[0211] The carrier 320 may be arranged on the transfer guide rail 310. The carrier 320 can move along the transfer guide rail 310. Therefore, the carrier 320 can be arranged in the loading area LA and the molding area PA.

[0212] The carrier 320 can be movably combined with the transfer guide rail 310. For example, the carrier 320 can be combined with the transfer guide rail 310 in a sliding manner, but it is not limited thereto. As long as it is a movable mechanism, the carrier 320 can be combined with the transfer guide rail 310 by any structure.

[0213] The carrier 320 may include a sliding portion 322 having a sliding structure and a placement surface 328 disposed on the opposite surface of the sliding portion 322. The sliding portion 322 may be combined with the transfer guide rail 310. The lower plate 510 may be placed on the placement surface 328. The placement surface 328 may face the lower plate 510.

[0214] The carrier 320 may be connected to the transfer driving unit 330. The transfer driving unit 330 may be connected to the thickness surface formed between the sliding portion 322 and the placement surface 328.

[0215] The transfer driving unit 330 may be disposed in the peripheral area SA. The transfer driving unit 330 is configured with an actuator that can move the carrier 320 to the loading area LA and the molding area PA. In this embodiment, the structure of the actuator moving back and forth is illustrated, but depending on the situation, the carrier 320 may be moved by a structure that moves left and right.

[0216] The support preparation device 10 for cartilage regeneration may include a pressing unit 400. The pressing unit 400 may be disposed on the molding area PA. The pressing unit 400 may include a pressing unit body 410, a pressing rod 420, a pressing plate 430, and a guide rod 440.

[0217] The pressing unit body 410 may be disposed on the upper surface of the frame body 210. The pressing unit body 410 may include an actuator. The actuator may move the pressing rod 420 in the up and down directions.

[0218] The pressing rod 420 may be disposed in a second through hole 215 that penetrates the upper and lower surfaces of the frame body 210. For example, the pressing rod 420 may be snapped into a second cylinder guide 216 disposed in the second through hole 215.

[0219] The pressing rod 420 may move in the up and down directions. The pressing rod 420 may move to contact the pressing plate 430. The pressing rod 420 may move the pressing plate 430 downward. When the target area faces the object to be molded, the pressing rod 420 may provide pressure to the pressing plate 430.

[0220] The pressing unit 400 may include a pressing plate 430 disposed between the frame body 210 and the workbench 120.

[0221] The pressing plate 430 may include an upper pressing plate surface 437 in contact with the pressing rod 420. The upper pressing plate surface 437 may have a placement portion 439. The pressing rod 420 may be placed on the placement portion 439.

[0222] The placement portion 439 may be disposed in an area including the center of gravity of the pressing plate 430. For example, when the pressing plate 430 is configured as a square, the center of gravity of the pressing plate 430 may be the middle area of the square. Therefore, the placement portion 439 may be disposed in the above middle area.

[0223] One end of the pressing rod 420 can be placed on the placement portion 439. The placement portion 439 can be formed of a material such as rubber or silicone that can withstand the pressing force on the upper surface 438 of the pressing plate.

[0224] In this way, when moving downward from the pressing rod 420, the pressing rod 420 can move the pressing plate 430 downward. And when the pressing plate 430 moves to the target location, the pressing rod 420 can apply a pressing force to the center of gravity of the pressing plate 430.

[0225] Guide rods 440 can be arranged around the pressing rod 420. The guide rods 440 can be arranged between the frame body 210 and the pressing plate 430.

[0226] One end of the guide rod 440 can be coupled to the pressing plate 430. The other side of the guide rod 440 can be inserted into the first through hole 212 that penetrates a part of the frame body 210. For example, a first cylinder guide 213 can be arranged in the first through hole 212 formed in the frame body 210. The guide rod 440 can be snapped into the first cylinder guide 213.

[0227] As described above, a plurality of first through holes 212 can be arranged symmetrically around the second through hole 215. A guide rod 440 can be arranged in each of the plurality of first through holes 212.

[0228] Therefore, the plurality of guide rods 440 can be arranged symmetrically around the pressing rod 420. The plurality of guide rods 440 can function to disperse the pressing force so that the molding unit 500 can form a uniform surface pressure. The plurality of guide rods 440 can apply a uniform pressing force to the whole surface of the pressing plate 430.

[0229] On the other hand, a gimbal member 450 can be arranged between the guide rod 440 and the pressing plate 430. For example, the gimbal member 450 can connect the lower surface of the guide rod 440 and the upper surface of the pressing plate 430. And the gimbal member 450 can also be selectively arranged between the placement portion 439 and the pressing plate 430. The gimbal member 450 can connect the lower surface of the placement portion 439 and the upper surface of the pressing plate 430.

[0230] The gimbal members 450 can be arranged symmetrically around the placement portion 439 with the placement portion 439 as the center. In other words, on the upper surface of the pressing plate 430, a plurality of guide rods 440 are arranged around the area including the center of gravity of the pressing plate 430, so the gimbal members 450 respectively arranged on the plurality of guide rods 440 can also be arranged with the same configuration structure.

[0231] The universal joint head 450 can adjust the inclination of the pressure plate 430. For example, the universal joint head 450 can adjust the level of the upper plate 520. That is, the universal joint head 450 can rotate the upper plate 520 (adjust the inclination).

[0232] When the inclination of the upper plate 520 is non-horizontal, the universal joint head 450 can rotate the upper plate 520 to adjust the level of the upper plate 520.

[0233] Therefore, the universal joint head 450 rotates the upper plate 520 (inclination) to adjust the level, and thus can provide the load of the upper plate 520 to the second mold (1200 in FIG. 18). For example, the upper plate 520 is combined with the pressure plate 430, so the load of the upper plate 520 and the pressure plate 430 can be provided to the second mold 1200.

[0234] The universal joint head 450 can adjust the pressure imbalance that may be caused by the thickness difference of the object to be molded. For example, when the thickness of the object to be molded is different, the universal joint head 450 can adjust the inclination of the pressure plate 430 so that the pressure plate 430 can correspond to the whole surface of one surface of the object to be molded.

[0235] Therefore, when the thickness of a part of the object to be molded is different from that of another part, the pressure plate 430 can prevent the pressure from concentrating on a part of the object to be molded or transfer more pressure.

[0236] In this way, the universal joint head 450 can adjust the inclination of the pressure plate 430 and improve the molding uniformity of the object to be molded.

[0237] The support preparation 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 dispersion part 550.

[0238] The lower plate 510 may be disposed on the upper surface of the carrier 320. For example, the lower plate 510 may be placed on the placement surface 328 of the carrier 320. The lower plate 510 can be formed in a shape similar to or smaller than the shape of the carrier 320.

[0239] The lower surface 512 of the lower plate 510 may be placed on the placement surface 328 of the carrier 320. The carrier 320 can move between the loading area LA and the molding area PA along the transfer rail 310. Therefore, the lower plate 510 placed on the carrier 320 can move between the loading area LA and the molding area PA through the carrier 320.

[0240] 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 (refer to 800 in FIG. 18) may 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.

[0241] The upper plate 520 may be disposed in the molding area PA. The upper plate 520 may be combined with the pressing plate 430. The upper plate 520 may include an upper plate bonding surface 527 that is combined with the pressing plate 430. For example, the upper plate bonding surface 527 may be combined with the lower surface 432 of the pressing plate 430. The lower surface 432 of the pressing plate may be a surface facing the upper surface 437 of the pressing plate where the placement portion 439 is disposed.

[0242] The upper plate 520 may be formed in a shape with an area larger than that of the lower plate 510. A molding object may 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 may be provided to the above-mentioned molding object. Therefore, the size of the above-mentioned molding object may be limited according to the shape of the lower plate 510.

[0243] As described above, the support preparation device 10 for cartilage regeneration according to the present invention can form a pressing plate 430 that disperses the pressing force to form a uniform pressing force, so that the area of the lower plate 510 can be increased. Therefore, the molding object disposed on the lower plate 510 can be formed in a large area.

[0244] The upper plate 520 may include an upper plate pressing surface 522 on the opposite side of the upper plate bonding surface 527. A pressure dispersion portion 550 may be disposed on the upper plate pressing surface 522.

[0245] The pressure dispersion portion 550 may be bonded to the upper plate pressing surface 522 by an adhesive. The pressure dispersion portion 550 may be formed of a silicon material, but is not limited thereto, and any material may be used as long as it can transmit pressure. The pressure dispersion portion 550 can uniformly disperse the pressing force input from the pressing plate 430 to the entire surface of the upper plate 520.

[0246] The support preparation 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 disposed in the peripheral area SA.

[0247] The support preparation device 10 for cartilage regeneration may include an input unit 600 for input provided by a staff member. For example, the input unit 600 may directly input a set value by a staff member.

[0248] The input unit 600 may include an input mechanism such as an input button for inputting set values. Among them, the set values may include, for example, the pressure of the pressing unit 400, the heating temperature of the lower plate 510, the pressure supply time and the heating time of the pressing unit 400, etc.

[0249] The display unit 700 may display the above set values on the screen. In other words, the display unit 700 may display the input information on the screen. For example, the display unit 700 may display the pressure of the pressing unit 400, the heating temperature of the lower plate 510, the pressure supply time, and the heating time, etc. by numerical values.

[0250] Moreover, in the space where the display unit 700 is arranged, a control unit for controlling the set values of the cartilage regeneration support preparation device 10 may also be arranged.

[0251] In this way, according to the embodiment of the present invention, the cartilage regeneration support preparation device 10 forms uniform pressure, so that a cartilage regeneration support with improved uniformity can be prepared.

[0252] Figure 7 It is a block diagram showing a cartilage regeneration support preparation device according to an embodiment of the present invention.

[0253] For avoiding repeated description and facilitating explanation, Figure 7 reference Figures 3 to 6 is made for explanation.

[0254] The cartilage regeneration support preparation device 10 according to an embodiment of the present invention may include a sensor unit 30 and a control unit 50.

[0255] The control unit 50 may be connected to the display unit 700, the input unit 600, and the sensor unit 30. The control unit 50 may be arranged in the area where the display unit 700 is arranged.

[0256] The control unit 50 may also be connected to the structure where the sensor unit 30 is arranged. For example, the control unit 50 may be connected to the structure where the pressure sensor 470 and / or the temperature sensor 515 are arranged.

[0257] As a specific example, when the temperature sensor 515 is arranged on the lower plate 510, the control unit 50 may be connected to the lower plate 510. As another example, when the pressure sensor 470 is arranged on the pressing unit 400, the control unit 50 may be connected to the pressing unit 400. The sensor unit 30 may include a pressure sensor 470. The pressure sensor 470 may be arranged on the upper surface of the frame body 210.

[0258] In this figure, a figure showing that the pressing unit 400 is provided with a pressure sensor 470 is used for explanation. Among them, the pressure sensor 470 may also be arranged in the molding unit 500.

[0259] The input unit 600 can receive input provided by the staff. The input unit 600 can input the provided pressure to the pressure rod 420 of the pressurizing unit 400. The provided input can be the set pressure for starting the pressurizing unit 400. The input unit 600 can form the first signal SG1 from the above-mentioned set pressure.

[0260] 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.

[0261] The control unit 50 can convert the first signal SG1 and transmit the first - 1 signal SG11 to the display unit 700. The display unit 700 that receives the first - 1 signal SG11 can display the set pressure on the screen.

[0262] Moreover, the control unit 50 can convert the first signal SG1 and transmit the first - 2 signal SG12 to the pressurizing unit 400.

[0263] The pressurizing unit 400 can be started according to the first - 2 signal SG12. For example, the pressurizing unit 400 can start the pressure rod 420 according to the first - 2 signal SG12. For example, according to the first - 2 signal SG12, the pressure rod 420 can move the pressure plate 430. When the pressure plate 430 moves and contacts the object to be molded according to the first - 2 signal SG12, the pressure rod 420 can provide pressure to the pressure plate 430.

[0264] 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 through the information of the pressure sensed in the pressurizing unit 400. The sensor unit 30 can transmit the second signal SG2 to the control unit 50.

[0265] The control unit 50 that receives the second signal SG2 can calculate whether the pressure is transmitted through the pressurizing unit 400 according to the information of the first - 2 signal SG12. For example, the control unit 50 can calculate the pressure set on the pressure rod 420 and the pressure difference transmitted from the pressure sensor 470. The control unit 50 can form the third signal SG3 and the fourth signal SG4 from the calculated pressure difference value (hereinafter referred to as "calculated value").

[0266] When the above - mentioned calculated value is within the error range compared with the measured data, the control unit 50 can transmit the fourth signal SG4 to the display unit 700. Moreover, the control unit 50 can generate the same third signal SG3 as the first - 2 signal SG12 and provide the third signal SG3 to the pressurizing unit 400.

[0267] On the other hand, when the above - mentioned calculated value exceeds the error range compared with the measured data, the control unit 50 can provide a corrected input value to the pressurizing unit 400.

[0268] Among them, when manually set by the control unit 50, a fourth signal SG4 formed by the above operation value can be transmitted to the display unit 700. The display unit 700 can display the above operation value according to the fourth signal SG4 on the screen.

[0269] The above operation value displayed on the display unit 700 can be confirmed by the staff. The staff can input a corrected input value to the input unit 600 based on the displayed information.

[0270] The control unit 50 can generate a third signal SG3 using the above corrected input value. 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 a corrected pressure value to the pressure plate 430. The above corrected pressure value can be the pressure provided to the pressure plate 430.

[0271] Moreover, the control unit 50 can generate a fourth - 1 signal SG41 based on the information according to the third signal SG3. The fourth - 1 signal SG41 can be provided to the display unit 700. The display unit 700 can display the information formed by the fourth - 1 signal SG41 on the screen.

[0272] In this way, the cartilage regeneration support preparation device 10 according to the present invention can control the pressure provided to the pressurizing unit 400 through the sensor unit 30.

[0273] On the other hand, when automatically set by the control unit 50, if there are differences in the calculated value of the above pressure difference (hereinafter referred to as "calculated value"), it is possible that the fourth signal SG4 is not generated.

[0274] The pressure sensor 470 can sense the pressure formed in the pressurizing unit 400. Through the above sensing information, the sensor unit 30 can generate a second - 1 signal SG21. The sensor unit 30 can transmit the second - 1 signal SG21 to the control unit 50.

[0275] The control unit 50 can determine based on the measured data that the above calculated value is included within the error range compared with the measured data. When it is determined to be within the error range, the control unit 50 can generate a third signal SG3 identical to the first - 2 signal SG12.

[0276] 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 the pressure according to the first - 2 signal SG12 to the pressure plate 430. The pressure according to the first - 2 signal SG12 can be the pressure provided to the pressure plate 430.

[0277] Furthermore, the control unit 50 can generate a fourth signal SG4 based on the 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 the information formed by the fourth signal SG4 on the screen.

[0278] In this way, the cartilage regeneration support preparation device 10 according to the present invention can control the pressure provided to the pressing unit 400 through the sensor unit 30.

[0279] On the other hand, the control unit 50 can compare the input pressure and the pressure provided to the molding object. For example, the pressing unit 400 can provide pressure to the molding unit 500. For example, the pressing unit 400 can transfer the pressure formed on the pressing plate 430 to the molding unit 500.

[0280] There may be a difference between the pressure formed in the pressing unit 400 and the pressure formed in the molding unit 500. The control unit 50 can compare the pressure provided in the pressing unit 400 and the pressure output in the molding unit 500. The above output pressure can be the pressure provided to the molding object.

[0281] The above-provided pressure can be provided to the molding unit 500 through the pressing plate 430. The above output pressure provided to the molding object can be formed by the molding unit 500.

[0282] The pressure sensors 470 of the sensor unit 30 can be respectively arranged in the pressing unit 400 and the molding unit 500. The pressure sensor 470 can sense the provided pressure of the pressing unit 400. And the pressure sensor 470 can sense the output pressure of the molding unit 500.

[0283] The sensor unit 30 can generate a second signal formed by the above-provided pressure and the above output pressure.

[0284] There may be a difference between the provided pressure input from the pressing rod 420 and the output pressure output from the molding unit 500 (hereinafter referred to as "pressure difference"). For example, a pressure difference may occur during the process of dispersing the pressure over the entire pressing plate 430 or during the process of dispersing the pressure in the pressure dispersion unit 550.

[0285] In this case, the probability of defective molding of the molded product may increase. And there may be a loss of power leakage in the use of the preparation device.

[0286] The pressure sensor 470 can sense the pressure in each set area, and the sensor unit 30 changes the pressure in each set area into a signal and transmits the second signal SG2 to the control unit 50.

[0287] The control unit 50 can calculate the above-mentioned pressure difference. The set value of the pressurizing unit 400 can be readjusted in response to the calculated value. Also, the bonding structure between the structures can be readjusted. Thus, the pressure sensor 470 can reduce the defective probability and the loss of power leakage in the manufacturing apparatus.

[0288] Figure 8 FIG. is a plan view showing the shape of the pressure plate of the pressurizing unit according to an embodiment of the present invention. Figure 9 FIG. is a plan view showing another shape of the pressure plate of the pressurizing unit according to an embodiment of the present invention. Figure 10 FIG. is a plan view showing another shape of the pressure plate of the pressurizing unit according to an embodiment of the present invention.

[0289] For the sake of avoiding redundant description and facilitating explanation, Figures 8 to 10 reference Figures 3 to 6 is made for explanation.

[0290] Referring to Figures 8 to 10 , the pressurizing unit 400 may include a pressurizing rod 420, a pressure plate 430, and a guide rod 440.

[0291] The pressure plate 430 may include a placement portion 439. The placement portion 439 may be disposed in a region including the center of gravity of the pressure plate 430. The pressurizing rod 420 may be disposed at a position corresponding to the placement portion 439.

[0292] The guide rod 440 may be disposed around the pressurizing rod 420. The guide rod 440 can be symmetrically disposed about the pressurizing rod 420. The symmetrically disposed guide rods 440 may form a pressing force dispersed over the entire surface of the pressure plate 430.

[0293] On the other hand, the lower plate 510 of the molding unit 500 can be configured in a shape with an area smaller than that of the upper plate 520. Also, the upper plate 520 can be combined with the pressure plate 430 in the same shape.

[0294] Thus, the pressing force provided from the pressure plate 430 having a dispersed pressing force can be transmitted to the upper plate 520. The upper plate 520 to which the pressing force is transmitted can press the molding object toward the lower plate 510.

[0295] Therefore, the pressure plate 430 having a pressing force dispersed over the entire surface can contribute to forming a uniform surface pressure on the molding unit 500.

[0296] In Figures 3 to 6 , the shape of the pressure plate 430 is rectangular, and the guide rods 440 can be symmetrically disposed on both sides of the pressurizing rod 420 about the pressurizing rod 420. Thus, two guide rods 440 can be disposed to be connected to the pressure plate 430.

[0297] Reference Figure 8 As shown in Figure 8 , the pressing plate 430 has the same quadrilateral shape, and the guide rods 440 can be symmetrically arranged around the pressing rod 420 in the corner regions of the pressing plate 430. Therefore, four guide rods 440 can be arranged to be connected to the pressing plate 430.

[0298] In this way, by symmetrically arranging the four guide rods 440 around the pressing rod 420 on the pressing plate 430, the dispersion degree of the pressing force can be further improved.

[0299] Reference Figure 9 As shown in Figure 9 , the pressing plate 430 can have a triangular shape. Three guide rods 440 can be arranged on the triangular pressing plate 430. For example, when the pressing plate 430 has a triangular shape, in order to symmetrically arrange the guide rods 440 around the pressing rod 420, the three guide rods 440 can be arranged on the pressing plate 430.

[0300] In this way, when the pressing plate 430 has a triangular shape, by symmetrically arranging the three guide rods 440 around the pressing rod 420 on the pressing plate 430, the dispersion degree of the pressure can be further improved.

[0301] Reference Figure 10 As shown in Figure 10 , the pressing plate 430 can have 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 illustrated.

[0302] Specifically, when the pressing plate 430 has a circular shape, in order to symmetrically arrange the guide rods 440 around the pressing rod 420, four to eight guide rods 440 can be arranged on the pressing plate 430.

[0303] In this way, when the pressing plate 430 has a circular shape, by symmetrically arranging the four to eight guide rods 440 around the pressing rod 420 on the pressing plate 430, the dispersion degree of the pressure can be further improved.

[0304] Figure 11 FIG. is a flowchart showing a method for preparing a cartilage regeneration support using a cartilage regeneration support preparation device according to an embodiment of the present invention. Figures 12 to 14 For Figure 11 each step of Figure 20 FIG. 15 to

[0305] is a process diagram showing a method for preparing a cartilage regeneration support using a cartilage regeneration support preparation device according to an embodiment of the present invention. Figures 11 to 20 For avoiding repeated description and for easy explanation, Figures 3 to 6 reference is made to

[0306] The method for preparing a support for cartilage regeneration according to an embodiment of the present invention can form a support for cartilage regeneration by using a support preparation device 10 for cartilage regeneration.

[0307] The support preparation device 10 for cartilage regeneration may include a transfer unit 300, a molding unit 500, and a pressing unit 400. The molding unit 500 may include an upper plate 520 and a lower plate 510. An object to be molded may be disposed between the upper plate 520 and the lower plate 510. The support preparation device 10 for cartilage regeneration may apply pressure to the object to be molded to form a support for cartilage regeneration with improved pattern uniformity on one or both sides.

[0308] Hereinafter, the present invention will be described in more detail through examples.

[0309] Embodiment

[0310] Example 1. Fabrication and uniformity measurement of a large-area PLGA sheet (single-sided pattern)

[0311] Use Figure 3 the preparation device to prepare a support for cartilage regeneration.

[0312] As Figure 1 shown, a single-sided PDMS mold (flat) is laid on a plate, and 12 ml of a PLGA solution (including 10 ml of chloroform and 2.5 g of PLGA) in which 25 g of PLGA is dissolved in 100 ml of chloroform is uniformly coated on a PUA mold (800 nm) in a size of 12 * 12 cm. Then, the PLGA solution is turned upside down so that it is located below and placed on the PDMS mold. Use Figure 3 the preparation device to apply pressure and perform pattern molding at room temperature for 40 minutes.

[0313] After the pattern molding is completed, the solution is lifted upward on a hot plate at 70 °C to evaporate the solvent (about 1 hour). The cured PLGA sheet is carefully separated from the PUA mold. After the separated large-area PLGA support is immersed in 70% ethanol for about 10 seconds, it is washed with purified water. After the washed support is dried for more than 8 hours, it is cut into a suitable size. The above process is repeated four more times to fabricate a total of five large-area PLGA sheets ( Figure 21 ).

[0314] Randomly measure the thicknesses at five locations of the five prepared large-area PLGA sheets, and record the average values of each different sample and the total average value of the measurement data ( Figure 22 ).

[0315] Example 2. Fabrication of a large-area PLGA sheet (double-sided pattern)

[0316] Use Figure 3The preparation device is used to prepare the support for cartilage regeneration.

[0317] As Figure 1 shown, a double-sided PDMS mold (800 nm) is laid on the plate, and 12 ml of a PLGA solution (including 10 ml of chloroform and 2.5 g of PLGA) in which 25 g of PLGA is dissolved in 100 ml of chloroform is uniformly coated on the PUA mold (800 nm) in a size of 12 * 12 cm. After that, the PLGA solution is turned upside down so that it is located below and placed on the PDMS mold. Using Figure 3 the preparation device to apply pressure, after setting the temperature to 50 °C, continuous pattern forming is carried out for 60 minutes.

[0318] After the pattern forming is completed, without separating the upper and lower molds, it is placed on the upper part of a hot plate at 70 °C, and then pressed with a steel plate of about 1.2 kg in a way to prevent the mold from separating, and it is dried for more than 5 hours. The solidified PLGA is carefully separated from the PDMS and PUA molds. The separated large-area PLGA support is immersed in 70% ethanol for about 10 seconds, and then washed three times with purified water. After drying the washed support by blowing air for about 30 minutes, it is cut into a suitable size. The above process is repeated four more times to make a total of five large-area PLGA sheets.

[0319] Example 3. Measuring the pattern between the grooves and ridges of the large-area PLGA sheet by FE-SEM imaging

[0320] Under the following conditions, the distance between the grooves and ridges of the nano-pattern and the uniformity of the pattern are measured for the sheets of Example 1 and Example 2 by FE-SEM imaging.

[0321] - Resolution: 0.6 nm

[0322] - Magnification: X20 - 2000000

[0323] - EDS detector (ATW2, 127 eV, 50 mm 2 )

[0324] As a result, the distances between each pattern and the ridges of the large-area sheets of Example 1 and Example 2 are 790 nm respectively, and the ridges and grooves maintain a ratio of 1:1 ( Figure 23 ). And, the deviation between five arbitrary points on the ridges and five arbitrary points on the grooves of the nano-pattern is less than 10 nm, and there is substantially no deviation.

Claims

1. A support for cartilage regeneration, Made of biocompatible polymers, A pattern for cartilage regeneration is formed on one or both sides. The above pattern is formed by repeated ridges and grooves. The area of ​​the pattern that satisfies the uniformity (U) of the following mathematical formula 1 is 95% or more of the total area, The above-mentioned support for cartilage regeneration is characterized in that: Mathematical formula 1 U=|H P1 -H P2 |≤0.1H n In the above mathematical formula, H P1 means the height in P1, H P2 means the height in P2, H n This means the height difference between the ridge and the groove of a normal pattern.

2. The support for cartilage regeneration according to claim 1, characterized in that The above-mentioned P1 and P2 are both located at the ridge portion or both located at the groove portion.

3. The support for cartilage regeneration according to claim 1, characterized in that The area satisfying the uniformity of the above-mentioned mathematical formula 1 is 99% or more of the total area.

4. The support for cartilage regeneration according to claim 1, characterized in that The thickness is 30μm to 100μm.

5. The support for cartilage regeneration according to claim 1, characterized in that The biocompatible polymer is one selected from the group consisting of polycaprolactone, polylactic acid-co-glycolic acid, polyethylene glycol, polyethylene oxide, polylactic acid and polyglycolic acid.

6. The support for cartilage regeneration according to claim 1, characterized in that The biocompatible polymer is a poly(lactic acid-glycolic acid) copolymer containing 65 mol% to 85 mol% of lactide and 15 mol% to 35 mol% of glycolide.

7. The support for cartilage regeneration according to claim 1, characterized in that The pattern is in the form of straight lines or curves in which the ridges and the grooves are arranged repeatedly in parallel.

8. The support for cartilage regeneration according to claim 1, characterized in that The single-side or double-side coating is 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, characterized in that Fibrin coated the edges.

10. A method for preparing a support for cartilage regeneration, wherein the support for cartilage regeneration is the support for cartilage regeneration according to any one of claims 1 to 9, characterized in that: The preparation method comprises: The step of applying a polymer solution including a biocompatible polymer onto a polyurethane acrylate mold to prepare a sheet-like semi-cured product; Applying pressure to the semi-cured product using a polydimethylsiloxane mold to prepare a patterned semi-cured product; and A step of drying the patterned semi-cured material.

11. The method for preparing a support for cartilage regeneration according to claim 10, characterized in that: The patterned semi-cured material is prepared by placing the semi-cured material between the polyurethane acrylate mold and the polydimethylsiloxane mold and then applying pressure using an upper plate and a lower plate.

12. The method for preparing a support for cartilage regeneration according to claim 10, characterized in that: The urethane acrylate mold or the polydimethylsiloxane mold is formed with projections and depressions for forming the pattern.

13. The method for preparing a support for cartilage regeneration according to claim 11, characterized in that: The upper plate has a pressurizing rod and a guide rod.

14. The method for preparing a support for cartilage regeneration according to claim 10, characterized in that: The above pressure is 0.40Pa to 0.70Pa.

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