Porous three-dimensional meniscus scaffolds and biodegradable medical devices comprising the same

Abstract

The present invention relates to a porous three-dimensional meniscus scaffold and a biodegradable medical device including the same, according to which, by appropriately adjusting the interval ratio between fibers inside the meniscus scaffold, an external force applied to the meniscus scaffold can be more stably and uniformly dispersed, as a result of which the biodegradable medical device including the meniscus scaffold is more structurally stable.

Description

Technical Field

[0001] This application claims priority to Korean Patent Application No. 10-2023-0151068, filed with the Korean Patent Office on November 3, 2023, the disclosure of which is incorporated herein by reference.

[0002] This invention relates to a porous three-dimensional meniscus stent and a biodegradable medical device including the same, and more specifically, to a porous three-dimensional meniscus stent with a more stable structure by appropriately adjusting the spacing ratio between fibers inside the meniscus stent, and a biodegradable medical device including the same. Background Technology

[0003] The meniscus acts as a cushion within the knee joint, consisting of two C-shaped fibrocartilage complexes located between the femoral condyle and the tibial plateau. The meniscus plays a crucial role in load transfer, load distribution, shock absorption, joint stability, and lubrication within the knee joint.

[0004] Figures 1a to 1c This is a diagram showing the axial force, tensile force, and hoop tension applied to the meniscus. (Refer to...) Figures 1a to 1c The meniscus must convert the compressive force exerted axially by the femur into a tensile force, while simultaneously distributing the force evenly. During this process, the meniscus experiences a radially outward pushing force, thus requiring the maintenance of good hoop tension to resist this force. To maintain this hoop tension, it must, like a normal meniscus, have strong fibers arranged circumferentially. The axial compressive force from the femur pushes the meniscus outward during its conversion into tensile force; therefore, preventing the meniscus from being pushed outward is crucial.

[0005] Such meniscus injuries can be caused by degenerative changes in the cartilage itself, various sports activities, and trauma, and are well known to be the most common type of knee injury. Although the meniscus is a human structure, its central third lacks blood vessels (white zone), only the peripheral third has blood vessels (red zone), and the presence of blood vessels in the middle third is uncertain (red-white zone). In meniscus injuries, the peripheral red zone, with its relatively favorable blood supply, can heal with suturing; however, the central white zone, lacking blood vessels and unable to heal, requires meniscectomy. Even with a meniscus tear, suturing remains the best treatment option whenever possible. However, if the tear is in an avascular area, or if the degeneration is too severe to suture, meniscectomy is necessary. After meniscectomy, if the meniscus defect is severe, allogeneic meniscus transplantation can be performed to restore structure. Although allogeneic meniscus transplantation is rare, it carries the risk of infection, makes it difficult to select grafts of precise size, and often faces supply shortages due to the use of human tissue.

[0006] Furthermore, research on natural or synthetic polymer scaffolds for implanting the meniscus has been ongoing in recent years. When artificial tissue made from biomaterial scaffolds used in tissue engineering is implanted, in the initial stages of implantation, the scaffold provides a foundation for the implanted tissue cells, preventing them from dying and maintaining their original function. Moreover, over time, the biodegradable polymers gradually disappear, and it should be possible to form a tissue composed solely of implanted cells that have fully adapted to the in vivo environment, with the same morphology and function as natural tissue.

[0007] On the other hand, in order to apply it to medical devices, the key is to achieve uniform force distribution while converting the axial force acting on the meniscus stent into tensile force. For this purpose, it is urgent to study and develop stable structures for each element that constitutes the meniscus stent. Summary of the Invention

[0008] [The problem the invention aims to solve]

[0009] The technical problem to be solved by the present invention is to provide a porous three-dimensional meniscus support that can stably and uniformly distribute the force acting on the meniscus support.

[0010] Furthermore, the technical problem to be solved by the present invention is to provide a biodegradable medical device comprising the aforementioned porous three-dimensional scaffold.

[0011] The problems to be solved by this invention are not limited to those mentioned above. For other problems not mentioned, those skilled in the art will also be able to understand them clearly from the following description.

[0012] [Methods used to solve problems]

[0013] According to an embodiment of the present invention for solving the above-mentioned problems, a porous three-dimensional meniscus scaffold is provided, comprising: a plurality of first axial layers, each including one or more first axial fibers formed at predetermined intervals along a first axial direction; and a plurality of second axial layers, each including one or more second axial fibers formed at predetermined intervals along a second axial direction. The first axial layers and the second axial layers are interleaved and stacked. In the (N+1)th first axial layer (where N is a natural number greater than or equal to 1), there exists any one first axial fiber a; in the Nth first axial layer, there exists a first axial fiber b most adjacent to the arbitrary first axial fiber a; and in the Nth first axial layer, there exists a first axial fiber c second closest to the arbitrary first axial fiber a. Assuming that in the Nth first axial layer there exists a first axial fiber a' formed by vertically moving from the arbitrary first axial fiber a to the Nth first axial layer, the ratio of the interval between the first axial fiber a' and the first axial fiber b to the interval between the first axial fiber a' and the first axial fiber c is 1:9 to 3:7.

[0014] In this case, either the first axial fiber or the second axial fiber can be stacked in a manner orthogonal to each other.

[0015] Furthermore, the first axial fiber b, the first axial fiber a', and the first axial fiber c can be arranged sequentially from the periphery towards the central side of the porous three-dimensional meniscus support.

[0016] Furthermore, the first axial fiber and the second axial fiber may each independently comprise one or more polymers selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic) acid (PLGA), polyurethane (PU), and polydioxane.

[0017] Furthermore, the width of the pores inside the porous three-dimensional meniscus support can be 1 mm to 2 mm, and the height of the pores can be 0.1 to 0.5 mm.

[0018] Furthermore, the porosity of the porous three-dimensional meniscus scaffold can be between 70% and 85%.

[0019] Moreover, the first axial fiber and the second axial fiber can each independently have a width of 270 μm to 330 μm.

[0020] In addition, the porous three-dimensional meniscus scaffold may also include circumferential fibers formed in a manner that wraps around the outer surface of the porous three-dimensional meniscus scaffold.

[0021] Moreover, the porous three-dimensional meniscus support can be manufactured using 3D printing equipment.

[0022] On the other hand, according to another embodiment of the present invention, a biodegradable medical device comprising the aforementioned porous three-dimensional meniscus stent of the present invention is provided.

[0023] [Invention Effects]

[0024] According to one embodiment of the present invention, by appropriately adjusting the spacing ratio between the fibers inside the meniscus support, the external force applied to the meniscus support can be distributed more stably and evenly.

[0025] As a result, biodegradable medical devices, including such meniscus stents, are structurally more stable.

[0026] On the other hand, the effects of the present invention are not limited to those described above, but should be understood to include all effects that can be inferred from the detailed description of the invention or the composition of the invention as set forth in the claims. Attached Figure Description

[0027] Figure 1a To illustrate the axial force applied to the meniscus, Figure 1b To illustrate the tensile force acting on the meniscus, Figure 1c A diagram illustrating the hoop tension acting on the meniscus.

[0028] Figure 2a The diagram illustrates a structure of a C-shaped porous three-dimensional meniscus scaffold that mimics a human meniscus, used to simulate an embodiment of the present invention. Figure 2b A diagram illustrating the dimensions of a meniscus support according to an embodiment of the present invention.

[0029] Figure 3The diagram illustrates a cross-sectional view of a meniscus support according to an embodiment of the present invention, and briefly shows the configuration relationship between any one of the first axial fibers a, b, and c of the N+1th first axial layer.

[0030] Figure 4 To illustrate, when an external force is applied... Figure 3 The diagram shows the magnitude of the resistance in the lateral and medial directions during meniscus stent placement.

[0031] Figure 5 The image shows the circular center line of an STL 3D model of a meniscus support according to an embodiment of the present invention, and also shows a diagram of the pore structure formed inside.

[0032] Figure 6 To illustrate the definition of an alternating ratio with multiple pore structures for evaluating stress concentration and stability based on the pore structure formed inside the meniscus support, a graph is shown showing the results of measuring the mechanical properties of the meniscus support before being subjected to external forces based on the alternating ratio.

[0033] Figure 7 This diagram illustrates and compares the stress distribution and deformation based on the alternating ratio when the meniscus support is compressed.

[0034] Figure 8 This is a chart showing the evaluation and comparison of peak stress distribution and deformation values ​​based on the alternating ratio when the meniscus support is compressed. Detailed Implementation

[0035] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, so that those skilled in the art can easily implement the invention.

[0036] The embodiments of the present invention described below are intended to explain the present invention more clearly to those skilled in the art. The scope of the present invention is not limited to the following embodiments, and the following embodiments can be modified in many different forms.

[0037] The terminology used in this specification is for illustrative purposes and is not intended to limit the invention. Unless the context explicitly states otherwise, singular terms used herein may include plural forms. Furthermore, the terms "comprise" and / or "comprising" as used herein are used to specify the presence of a particular shape, step, number, action, component, element, and / or combination thereof, but do not exclude the presence or addition of more than one other shape, step, number, action, component, element, and / or combination thereof. Additionally, the term "connected" as used herein means not only that certain components are directly connected to each other, but also includes the concept of indirect connection between components through the further provision of other components.

[0038] Furthermore, when this specification mentions a component being "above" other components, it includes not only situations where the component is in contact with other components, but also situations where another component exists between the two components. The term "and / or" as used in this specification includes any one of the listed items and all combinations thereof. In addition, terms indicating degree such as "about," "substantially," etc., used in this specification are taken into account inherent manufacturing and material tolerances, and are used within the scope of their numerical or degree range or in a meaning similar to that thereof, to prevent improper use by infringers of the disclosures mentioned with precise or absolute values ​​provided to aid in understanding this application.

[0039] Figure 2a The diagram illustrates a structure used to simulate a C-shaped porous three-dimensional meniscus support that mimics a human meniscus, according to an embodiment of the present invention. Figure 2b The diagram illustrates the dimensions of a meniscus support according to an embodiment of the present invention. As an example, the dimensions of the manufactured meniscus support are 45.2mm × 31.5mm × 8.0mm. Figure 3 The diagram illustrates a cross-section of a meniscus support according to an embodiment of the present invention, and schematically shows the configuration relationship between any one of the first axial fibers a, b, and c of the N+1th first axial layer.

[0040] Referring to the accompanying drawings, a porous three-dimensional meniscus scaffold of one aspect of the present invention includes: a plurality of first axial layers, each including one or more first axial fibers formed at predetermined intervals along a first axial direction; and a plurality of second axial layers, each including one or more second axial fibers formed at predetermined intervals along a second axial direction. The first axial layers and the second axial layers are stacked interleaved with each other. In the (N+1)th (where N is a natural number greater than or equal to 1) first axial layer, there exists any one first axial fiber a; in the Nth first axial layer, there exists a first axial fiber b most adjacent to the arbitrary first axial fiber a; and in the Nth first axial layer, there exists a first axial fiber c second closest to the arbitrary first axial fiber a. Assuming that in the Nth first axial layer there exists a' formed by vertically moving from the arbitrary first axial fiber a to the Nth first axial layer, the ratio of the interval between the first axial fiber a' and the first axial fiber b to the interval between the first axial fiber a' and the first axial fiber c is 1:9 to 3:7.

[0041] Thus, if the ratio of the spacing between the first axial fiber a' and the first axial fiber b to the spacing between the first axial fiber a' and the first axial fiber c satisfies the range of 1:9 to 3:7, then when an external force is applied, compared to cases exceeding the range of values, the stress will not be concentrated in a certain part but will be evenly distributed, resulting in minimal deformation in the structure.

[0042] In this case, the ratio of the spacing between the first axial fiber a' and the first axial fiber b to the spacing between the first axial fiber a' and the first axial fiber c can be specifically 1.5:8.5 to 2.5:7.5, more specifically 2:8.

[0043] The first axial fiber and the second axial fiber can be stacked orthogonally to each other. In this case, the angle formed by the first axial fiber and the second axial fiber can be 60° to 120°, 70° to 110°, 80° to 100°, or more specifically, around 90°.

[0044] Furthermore, the first axial fiber b, the first axial fiber a', and the first axial fiber c can be arranged sequentially from the periphery towards the central side of the porous three-dimensional meniscus support.

[0045] Reference Figure 3 and Figure 4When an external force, specifically an axial force, is applied to the meniscus support structure, the tensile force acting on it is stronger towards the central direction and relatively weaker towards the peripheral direction. Furthermore, regarding the force resisting this external force, the resistance is stronger towards the peripheral direction and weaker towards the central direction. As a result, the applied external force is evenly distributed, the ring tension is well maintained, and the meniscus can be stably held in place.

[0046] On the other hand, the first axial fiber and the second axial fiber can each be independently a biodegradable polymer, specifically including one or more polymers selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic) acid (PLGA), polyurethane (PU), and polydioxane, more specifically polycaprolactone (PCL), but not limited thereto.

[0047] Figure 5 The image shows the circular center line of an STL 3D model of a meniscus support according to an embodiment of the present invention, and also shows a diagram of the pore structure formed inside.

[0048] Reference Figure 5 It can be confirmed that the calculated correlation coefficient between the centerline of the STL 3D model of the meniscus stent and the circular function is R. 2 =0.997, almost close to 1. Based on this result, it can be confirmed that the shape can be optimized by rotating the cross-section of the meniscus support, and that 3D modeling can be optimized using cross-sections (n=6) from an STL file. The advantage of such an optimized model is that it allows for explicit definition of the centerline-based cross-section and the use of the same structure throughout the entire range.

[0049] In this case, the width of the pores within the porous three-dimensional meniscus stent can be approximately 1 mm to 2 mm, 1.25 mm to 1.75 mm, or 1.5 mm, and the height of the pores can be approximately 0.1 mm to 0.5 mm, 0.2 mm to 0.4 mm, or 0.3 mm. Furthermore, the volume fraction of the porous three-dimensional meniscus stent can be approximately 15% to 30%, 15% to 25%, or 20%, and the porosity of the meniscus stent can be approximately 70% to 85%, 75% to 85%, or around 80%.

[0050] When the above numerical range is met, the external force applied to the meniscus stent can be distributed more stably and evenly, resulting in more structurally stable biodegradable medical devices, including such meniscus stents.

[0051] The porous three-dimensional meniscus support of the present invention can be manufactured using 3D printing equipment.

[0052] When polycaprolactone (PCL) polymer is output using a 3D printing device, its line width can be controlled by the extrusion pressure. In this case, the line width can subsequently correspond to the width of the first axial fiber and the second axial fiber. When the line width is around 270 μm to 330 μm, 280 μm to 320 μm, 290 μm to 310 μm, or 300 μm, the deviation of the extrusion pressure can be minimized.

[0053] Therefore, the first axial fiber and the second axial fiber included in the meniscus support of the present invention can each independently have a width of about 270 μm to 330 μm, 280 μm to 320 μm, 290 μm to 310 μm or 300 μm.

[0054] To perform analytical analysis based on Hooke's Law and governing equations, the physical properties of polycaprolactone (PCL) can be defined using its density and stress-strain curves. It can be confirmed that the density of PCL is 1096 kg·m³. -3 The Young's modulus is 320.8 MPa, and the plastic property exhibits multilinear characteristics.

[0055] On the other hand, the meniscus support of the present invention is characterized in that, when any one of the first axial fibers of the (N+1)th first axial layer is moved vertically to the Nth first axial layer, it will not overlap with any one of the first axial fibers of the Nth first axial layer. This structure can be defined as an alternate structure. Conversely, when any one of the first axial fibers of the (N+1)th first axial layer is moved vertically to the Nth first axial layer, if it overlaps with the first axial fiber of the Nth first axial layer, this structure is defined as a non-alternate structure.

[0056] For the two groups of cases, the compressive stress, radial stress, and hoop stress of each group as the internal pore size changes can be analyzed. The results confirm that both groups exhibit anisotropy as the pore size increases. Furthermore, it can be confirmed that the alternating structure exhibits anisotropy more similar to that of a living organism compared to the non-alternate structure.

[0057] More specifically, in an alternating structure, compressive stress can be reduced, thus preventing further degeneration of the cartilage after meniscus transplantation.

[0058] On the other hand, the porous three-dimensional meniscus support of the present invention may also include circumferential fibers formed in a manner that surrounds the outer surface of the porous three-dimensional meniscus support.

[0059] By introducing the circumferential fibers, the meniscus support structure can be made similar to the collagen fibers of a normal meniscus, and the tensile hoop stress can be enhanced, thereby forming a more stable structure.

[0060] In other words, if, as shown in this invention, the structure satisfies both the alternating structure and contains circumferential fibers, it can exhibit a structure with reduced compressive stress and increased tensile modulus, thus forming a more cohesive and robust structure.

[0061] Figure 6To illustrate the definition of an alternating ratio with multiple pore structures for evaluating stress concentration and stability based on the pore structure formed inside the meniscus support, a graph is shown showing the results of measuring the mechanical properties of the meniscus support before being subjected to external forces based on the alternating ratio.

[0062] Reference Figure 6 The load on the human body is distributed by the meniscus. Therefore, it can be expected that there is an optimal ratio that can improve stress concentration and distribution and enhance stability based on the alternating ratio. Based on this, the ratio can be defined as five groups: 1:4, 2:3, 1:1, 3:2, and 4:1.

[0063] The alternation ratio can be defined as the ratio of the spacing between the first axial fiber a' and the first axial fiber b, as defined in the present invention, to the spacing between the first axial fiber a' and the first axial fiber c. It can be confirmed that the volume fraction of the five groups is adjusted to approximately 19.3% (porosity of 80.7%), and that the anisotropy of the five groups remains largely unchanged and is unrelated to the alternation ratio.

[0064] on the other hand, Figure 7 This diagram illustrates and compares the stress distribution and deformation based on the alternation ratio when the meniscus support is compressed.

[0065] Since there are no other knee joint tissues, such as femoral cartilage, tibial cartilage, and tibia, the applied external force is not defined as twice the human body load (1150N), but is defined as 100N for simulation.

[0066] Simulation results confirm that the 1:4 group has the fewest stress concentration areas and exhibits the smallest deformation in terms of maximum shear stress, compressive stress, equivalent stress (Von-Mises stress), and hoop stress.

[0067] Figure 8This is a chart showing the evaluation and comparison of peak stress distribution and deformation values ​​based on the alternating ratio when the meniscus support is compressed.

[0068] Reference Figure 8 Peak stress and deformation were measured for five groups with different alternating ratios to predict load-based fracture. The results showed that the 1:4 group exhibited lower values ​​in most cases.

[0069] More specifically, the peak compression stress in the 1:4 group was measured to be 27.871 MPa, peak shear stress to be 9.7987 MPa, peak equivalent stress to be 17.305 MPa, peak hoop stress to be 3 MPa, and peak deformation to be 0.1303 mm. These results are significantly lower than those of the other groups. Therefore, it can be confirmed that the structure is most stable when the alternation ratio is approximately 1:4.

[0070] On the other hand, another aspect of the biodegradable medical device of the present invention is characterized by including the aforementioned porous three-dimensional meniscus stent of the present invention.

[0071] The medical device may be a device that partially contacts the surface of a living organism or can be implanted into a living organism, and its purpose may be to induce the regeneration of surrounding tissues or cells at the contact or implantation site. More specifically, the biodegradable medical device may be a structure for tissue transplantation, a biomimetic tissue, etc., but is not limited to these.

[0072] Preferred embodiments of the present invention are disclosed in this specification. Although specific terminology is used, it is only for the purpose of illustrating the technical content of the invention and aiding in understanding the invention, and is not intended to limit the scope of the invention. In addition to the embodiments disclosed herein, other modifications can be implemented based on the technical concept of the invention, which will be apparent to those skilled in the art. For example, those skilled in the art will recognize that the porous three-dimensional meniscus support of the embodiments can be modified in various ways. Therefore, the scope of the invention should not be defined by the described embodiments, but rather by the technical concept set forth in the claims.

Claims

1. A porous three-dimensional meniscus support, comprising: A plurality of first axial layers, comprising one or more first axial fibers spaced apart along a first axial direction at predetermined intervals, and A plurality of second axial layers, comprising one or more second axial fibers formed at predetermined intervals along a second axial direction; The first axial layer and the second axial layer are stacked in an intersecting manner; In the N+1th first axial layer, there is any first axial fiber (a), in the Nth first axial layer there is a first axial fiber (b) that is closest to the first axial fiber (a), and in the Nth first axial layer there is a first axial fiber (c) that is second closest to the first axial fiber (a), where N is a natural number greater than 1. Assuming that there is a first axial fiber (a') in the Nth first axial layer formed by the vertical movement of any one of the first axial fibers (a) to the Nth first axial layer, then the ratio of the interval between the first axial fiber (a') and the first axial fiber (b) to the interval between the first axial fiber (a') and the first axial fiber (c) is 1:9 to 3:

7.

2. The porous three-dimensional meniscus support according to claim 1, wherein, The first axial fiber and the second axial fiber are stacked in an orthogonal manner.

3. The porous three-dimensional meniscus support according to claim 1, wherein, The first axial fiber (b), the first axial fiber (a'), and the first axial fiber (c) are arranged sequentially from the edge side toward the center side of the porous three-dimensional meniscus support.

4. The porous three-dimensional meniscus support according to claim 1, wherein, The first axial fiber and the second axial fiber each independently comprise one or more polymers selected from the group consisting of: polycaprolactone, polyglycolic acid, polylactic acid, polylactic acid-glycolic acid copolymer, polyurethane, and polydioxane.

5. The porous three-dimensional meniscus support according to claim 1, wherein, The width of the pores inside the porous three-dimensional meniscus support is 1mm to 2mm. The height of the pores is 0.1 mm to 0.5 mm.

6. The porous three-dimensional meniscus support according to claim 1, wherein, The porosity of the porous three-dimensional meniscus scaffold is 70% to 85%.

7. The porous three-dimensional meniscus support according to claim 1, wherein, The first axial fiber and the second axial fiber each have an independent width of 270 μm to 330 μm.

8. The porous three-dimensional meniscus support according to claim 1, wherein, The porous three-dimensional meniscus scaffold also includes circumferential fibers, which are formed by wrapping around the outer surface of the porous three-dimensional meniscus scaffold.

9. The porous three-dimensional meniscus support according to claim 1, wherein, The porous three-dimensional meniscus support is manufactured using 3D printing equipment.

10. A biodegradable medical device comprising a porous three-dimensional meniscus stent according to any one of claims 1 to 9.

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