Porous three-dimensional meniscus scaffold and biodegradable medical device comprising same

Abstract

The present invention relates to a porous three-dimensional meniscus scaffold and a biodegradable medical device comprising same. According to the present invention, external force applied to the meniscus scaffold can be more reliably and evenly dispersed by appropriately adjusting a ratio of intervals between fibers inside the meniscus scaffold, and thus the biodegradable medical device comprising the meniscus scaffold has greater structural stability.

Description

Porous three-dimensional meniscus scaffold and biodegradable medical device comprising the same

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

[0002] The present invention relates to a porous three-dimensional meniscus scaffold and a biodegradable medical device comprising the same, and more particularly, to a porous three-dimensional meniscus scaffold having a more stable structure by appropriately controlling the ratio of the gaps between fibers within the meniscus scaffold and a biodegradable medical device comprising the same.

[0003] The meniscus, a semilunar cartilage, is a C-shaped fibrocartilaginous structure found between the femoral head and the tibia, acting as a cushion within the knee joint. It plays a crucial role in load transfer, load distribution, shock absorption, joint stability, and lubrication.

[0004] Figures 1a to 1c are diagrams showing the axial force, tensile force, and hoop tension applied to the meniscus. Referring to Figures 1a to 1c, the meniscus must evenly distribute the compressive force applied as an axial force from the femur by converting it into a tensile force. At this time, a force pushing outward in a radial direction is applied to the meniscus, and the hoop tension that resists this force must be well maintained. In order for the hoop tension to be well maintained, strong fibers must be arranged in the circumferential direction like a normal meniscus. The axial compressive force applied from the femur is converted into a tensile force and pushes the meniscus outward, but it is very important to prevent the meniscus from being pushed outward.

[0005] Meniscus injuries can be caused by degenerative changes in the cartilage itself, various athletic activities, and trauma, and are known to be the most common knee joint injury. Although the meniscus is a structure within the human body, its central third is avascular (white zone), only about one-third of its margin is vascular (red zone), and the middle third has unclear vascularity (red-white zone). When the meniscus is damaged, repair is possible in the red zone, the peripheral area with relatively good blood supply. However, meniscectomy is often performed in the central white zone, where healing is difficult due to the absence of blood vessels. While suturing is the optimal treatment for a meniscus tear, if possible, meniscectomy is recommended for tears in avascular areas or when degenerative changes are so severe that suturing is impossible. If the meniscus is severely damaged after a meniscus resection, an allograft may be performed to restore its structure. While rare, allograft meniscus carries the risk of infection, and selecting the correct graft size can be challenging. Because it is human tissue, its availability is often limited.

[0006] Furthermore, recent research is underway on transplanting natural or synthetic polymer scaffolds in the form of meniscus. When artificial tissues are transplanted into the body using biomaterial scaffolds used in tissue engineering, the scaffold initially provides a foundation for transplanted tissue cells to survive and maintain their original function within the body. Over time, the biodegradable polymer gradually degrades, allowing the transplanted cells, which have fully adapted to the body, to form tissues with the same form and function as natural tissues.

[0007] Meanwhile, in order to apply it as a medical device, it is important to evenly distribute the axial force acting on the meniscus scaffold while converting it into tensile force. To this end, research and development on the stable structure of the elements that make up the meniscus scaffold is necessary.

[0008] The technical problem to be achieved by the present invention is to provide a porous three-dimensional meniscus scaffold that can more stably and evenly distribute the force acting on the meniscus scaffold.

[0009] In addition, the technical problem to be achieved by the present invention is to provide a biodegradable medical device including the aforementioned porous three-dimensional meniscus scaffold.

[0010] The problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0011] According to embodiments of the present invention for achieving the above-described task, a plurality of first axial layers including one or more first axial fibers formed at a predetermined interval along a first axial direction; And a plurality of second axial layers including one or more second axial fibers formed at a predetermined interval along the second axial direction, wherein the first axial layer and the second axial layer are laminated while crossing each other, and among the N+1 (wherein, N is a natural number greater than or equal to 1, and the same applies hereinafter) first axial layer, there are any first axial fibers (a), among the Nth first axial layer, there are any first axial fibers (b), and among the Nth first axial layer, there are any first axial fibers (a) first adjacent to the first axial fibers (b), and among the Nth first axial layer, there are any first axial fibers (c) second adjacent to the first axial fibers (a), and when it is assumed that any first axial fibers (a) have vertically moved (a') to the Nth first axial layer, the ratio between the interval between (a') and (b) and the interval between (a') and (c) is 1:9 to 3:7. A scaffold is provided.

[0012] At this time, the first axial fiber and the second axial fiber may be laminated in a form that is orthogonal to each other.

[0013] And, the above (b), the above (a') and the above (c) may be positioned sequentially from the peripheral side to the central side of the porous three-dimensional meniscus scaffold.

[0014] In addition, the first axial fiber and the second axial fiber may independently include at least one polymer selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic) acid (PLGA), polyurethane (PU), and polydioxane.

[0015] In addition, the width of the pores present inside the porous three-dimensional meniscus scaffold may be 1 mm to 2 mm, and the height of the pores may be 0.1 to 0.5 mm.

[0016] Additionally, the porosity of the porous three-dimensional meniscus scaffold may be 70% to 85%.

[0017] And, the first axial fiber and the second axial fiber may independently have a width of 270 μm to 330 μm.

[0018] Additionally, the porous three-dimensional meniscus scaffold may further include circumferential fibers formed to surround its outer surface.

[0019] In addition, the porous three-dimensional meniscus scaffold may be manufactured using a 3D printer.

[0020] Meanwhile, according to another embodiment of the present invention, a biodegradable medical device comprising a porous three-dimensional meniscus scaffold according to the present invention is provided.

[0021] According to one embodiment of the present invention, by appropriately controlling the ratio of the spacing between fibers within the meniscus scaffold, the external force applied to the meniscus scaffold can be more stably and evenly distributed.

[0022] As a result, biodegradable medical devices incorporating these meniscus scaffolds are structurally more stable.

[0023] Meanwhile, the effects of the present invention are not limited to the above-described effects, and should be understood to include all effects that can be inferred from the detailed description of the present invention or the composition of the invention described in the claims.

[0024] Figure 1a is a drawing showing the axial force applied to the meniscus, Figure 1b is a drawing showing the tensile force applied to the meniscus, and Figure 1c is a drawing showing the hoop tension applied to the meniscus.

[0025] FIG. 2a is a drawing showing a structure used for simulation of a C-shaped porous three-dimensional meniscus scaffold according to one embodiment of the present invention that mimics a human meniscus, and FIG. 2b is a drawing showing the dimensions of a meniscus scaffold according to one embodiment of the present invention.

[0026] FIG. 3 is a cross-section of a meniscus scaffold according to one embodiment of the present invention, and is a drawing schematically showing the arrangement relationship between any first axial fiber (a) of the N+1-th first axial layer, and the first axial fiber (b) and the first axial fiber (c) of the N-th first axial layer.

[0027] Figure 4 is a drawing schematically showing the magnitude of the force resisting in the outer and inner directions when an external force is applied to the meniscus scaffold of Figure 3.

[0028] FIG. 5 is a drawing showing the center line (circular center line) of an STL 3D model of a meniscus scaffold according to one embodiment of the present invention through image processing and showing a pore structure formed inside.

[0029] Figure 6 is a drawing showing the definition of an alternate ratio to have various pore structures in order to evaluate stress concentration and stability according to the structure of pores formed inside a meniscus scaffold, and the results of measuring mechanical properties before an external force is applied to the meniscus scaffold according to the alternate ratio.

[0030] Figure 7 is a drawing showing the stress distribution and deformation evaluated and compared according to the alternate ratio when compressing a meniscus scaffold.

[0031] Figure 8 is a graph showing the peak stress distribution value and deformation value compared according to the alternate ratio when the meniscus scaffold is compressed.

[0032] Hereinafter, with reference to the attached drawings, embodiments of the present invention will be described in detail so that a person having ordinary skill in the art to which the present invention pertains can easily practice the invention.

[0033] The embodiments of the present invention described below are provided to more clearly explain the present invention to a person having ordinary skill in the art, and the scope of the present invention is not limited by the following embodiments, and the following embodiments can be modified in various other forms.

[0034] The terminology used herein is used to describe particular embodiments and is not intended to limit the present invention. The singular forms used herein may include the plural forms unless the context clearly dictates otherwise. In addition, the terms "comprise" and / or "comprising" used herein specify the presence of a stated feature, step, number, operation, element, element, and / or group thereof, but do not exclude the presence or addition of one or more other features, steps, numbers, operations, elements, elements, and / or groups thereof. In addition, the term "connected" used herein not only means that certain elements are directly connected, but also includes a concept that indirectly connects elements by interposing another element between them.

[0035] In addition, when it is said in this specification that a certain element is located "on" another element, this includes not only cases where a certain element is in contact with another element, but also cases where another element exists between the two elements. The term "and / or" as used in this specification includes any one of the listed items and any and all combinations of one or more of them. In addition, terms of degree such as "about", "substantially", etc. as used in this specification are used to mean a range of or close to the numerical value or degree, taking into account inherent manufacturing and material tolerances, and are used to prevent infringers from unfairly using the disclosure that mentions exact or absolute numbers provided to help the understanding of this specification.

[0036]

[0037] FIG. 2a is a drawing showing a structure used for the simulation of a C-shaped porous three-dimensional meniscus scaffold according to an embodiment of the present invention that mimics a human meniscus, and FIG. 2b is a drawing showing the dimensions of a meniscus scaffold according to an embodiment of the present invention, and as an example, the dimensions of the manufactured meniscus scaffold are 45.2 mm × 31.5 mm × 8.0 mm. FIG. 3 is a drawing showing a cross-section of a meniscus scaffold according to an embodiment of the present invention, and schematically showing the arrangement relationship between any first axial fiber (a) of the (N+1)-th first axial layer, the first axial fiber (b) of the N-th first axial layer, and the first axial fiber (c).

[0038] Referring to the above drawings, a porous three-dimensional meniscus scaffold according to one aspect of the present invention comprises: a plurality of first axial layers including one or more first axial fibers formed at a predetermined interval along a first axial direction; And it has a plurality of second axial layers including one or more second axial fibers formed at a predetermined interval along the second axial direction, wherein the first axial layer and the second axial layer are laminated while crossing each other, and among the N+1 (wherein, N is a natural number greater than or equal to 1, and the same applies hereinafter) first axial layer, there are any first axial fibers (a), among the Nth first axial layer, there are any first axial fibers (b), and among the Nth first axial layer, there are any first axial fibers (a) that are first adjacent to the first axial fibers (b), and among the Nth first axial layer, there are any first axial fibers (c) that are second adjacent to the first axial fibers (a), and when it is assumed that the any first axial fibers (a) have vertically moved (a') to the Nth first axial layer, the ratio between the interval between (a') and (b) and the interval between (a') and (c) is 1:9 to 3:7.

[0039] In this way, when the ratio between the interval between (a') and (b) and the interval between (a') and (c) satisfies the range of 1:9 to 3:7, when an external force is applied, the stress is not concentrated on one part but is evenly distributed compared to when the numerical range is out of the range, and structurally, it shows the least deformation.

[0040] At this time, the ratio between the interval between (a') and (b) and the interval between (a') and (c) may be specifically 1.5:8.5 to 2.5:7.5, and more specifically 2:8.

[0041] Here, the arbitrary first axial fiber and the second axial fiber may be laminated in a form that is orthogonal to each other. At this time, the angle formed by the arbitrary first axial fiber and the second axial fiber may be 60° to 120°, 70° to 110°, 80° to 100°, and more specifically, may be approximately 90°.

[0042] In addition, the above (b), the above (a'), and the above (c) may be positioned sequentially from the peripheral side to the central side of the porous three-dimensional meniscus scaffold.

[0043] Referring to FIGS. 3 and 4, when an axial force is applied to the meniscus scaffold, the tensile force acting on the meniscus scaffold acts more strongly in the central direction and relatively weakly in the peripheral direction. In addition, with respect to the force resisting the external force, the resisting force becomes stronger in the peripheral direction and becomes weaker in the central direction. As a result, the applied external force is evenly distributed, the hoop tension is well maintained, and the meniscus can be stably maintained.

[0044] Meanwhile, the first axial fiber and the second axial fiber may be independently a biodegradable polymer, and specifically, may include at least one polymer selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), polylactide (PLA), poly(lactic-co-glycolic) acid (PLGA), polyurethane (PU), and polydioxane, and more specifically, may be polycaprolactone (PCL), but is not limited thereto.

[0045] FIG. 5 is a drawing showing the center line (circular center line) of an STL 3D model of a meniscus scaffold according to one embodiment of the present invention through image processing and showing a pore structure formed inside.

[0046] Referring to Figure 5, the correlation coefficient between the center line of the STL 3D model of the meniscus scaffold and the circle function was calculated as R 2= 0.997, which is close to 1. Based on these results, it can be confirmed that optimization is possible with a rotated cross-section of the meniscus scaffold, and optimized 3D modeling can be performed using the cross-section (n=6) of the STL file. This optimized model has the advantage of clearly defining the cross-section based on the centerline and applying the same structure across the entire range.

[0047] At this time, the width of the pores existing inside the porous three-dimensional meniscus scaffold may be about 1 mm to 2 mm, 1.25 mm to 1.75 mm, or 1.5 mm, and the height of the pores may be about 0.1 to 0.5 mm, 0.2 to 0.4 mm, or 0.3 mm. In addition, the volume fraction of the porous three-dimensional meniscus scaffold may be about 15% to 30%, 15% to 25%, or 20%, and the porosity of the meniscus scaffold may be about 70% to 85%, 75% to 85%, or 80%.

[0048] When these numerical ranges are satisfied, the external force applied to the meniscus scaffold can be more stably and evenly distributed, and as a result, the biodegradable medical device including the meniscus scaffold becomes more structurally stable.

[0049] The porous three-dimensional meniscus scaffold according to the present invention may be manufactured using a 3D printer.

[0050] The line width of polycaprolactone (PCL) polymer output using a 3D printer can be controlled by extrusion pressure. At this time, the line width can correspond to the widths of the first axial fiber and the second axial fiber in the future. When the line width is about 270 ㎛ to 330 ㎛, 280 ㎛ to 320 ㎛, 290 ㎛ to 310 ㎛, or 300 ㎛, it can be confirmed that the extrusion pressure deviation is the lowest.

[0051] Accordingly, the first axial fiber and the second axial fiber included in the meniscus scaffold according to the present invention may independently have a width of about 270 µm to 330 µm, 280 µm to 320 µm, 290 µm to 310 µm, or 300 µm.

[0052] In order to interpret based on Hooke's law and governing equation, the properties of polycaprolactone (PCL) can be defined through the density and strain-stress graph of PCL, and the density of PCL is 1,096 kgm -3 , Young's modulus is 320.8 Mpa, and it can be confirmed that the plastic property is multi-linear.

[0053] Meanwhile, the meniscus scaffold support according to the present invention is characterized in that when any first axial direction fiber of the N+1-th first axial direction layer is vertically moved to the N-th first axial direction layer, it does not overlap with any first axial direction fiber of the N-th first axial direction layer, and such a structure can be defined as an alternate structure. Conversely, when any first axial direction fiber of the N+1-th first axial direction layer is vertically moved to the N-th first axial direction layer, it overlaps with the first axial direction fiber of the N-th first axial direction layer, and such a structure can be defined as a non-alternate structure.

[0054] For the two groups above, the compressive stress, radial stress, and hoop stress of each group can be analyzed according to the internal pore size, and as a result, it can be confirmed that both groups exhibit anisotropy as the pore size increases, and it can be confirmed that anisotropy that is more similar to a living body is exhibited in the alternate structure than in the non-alternate structure.

[0055] More specifically, the alternate structure may prevent further cartilage degeneration after meniscus transplantation because the compressive stress may be reduced.

[0056] Meanwhile, the porous three-dimensional meniscus scaffold according to the present invention may further include circumferential fibers formed to surround its outer surface.

[0057] The introduction of the above-mentioned circumferential fibers can make the structure similar to that of the collagen fibers of a normal meniscus, and can strengthen the tensile hoop stress, thereby forming a more stable structure.

[0058] That is, when an alternate structure like the present invention is satisfied and all peripheral fibers are included, the compressive stress is reduced, the tensile modulus is increased, and a more condensed and solid structure can be exhibited.

[0059] Figure 6 is a drawing showing the definition of an alternate ratio to have various pore structures in order to evaluate stress concentration and stability according to the structure of pores formed inside a meniscus scaffold, and the results of measuring mechanical properties before an external force is applied to the meniscus scaffold according to the alternate ratio.

[0060] Referring to Figure 6, since the load of the human body is distributed by the meniscus, it can be expected that there will be an optimal ratio that can improve stress concentration distribution and stability according to the alternate ratio, and accordingly, a total of five groups of 1:4, 2:3, 1:1, 3:2, and 4:1 can be defined.

[0061] Here, the alternate ratio can be defined as the ratio between the interval between (a') and (b) defined in the present invention and the interval between (a') and (c), and it can be confirmed that the volume fraction of all five groups is adjusted to be close to 19.3% (porosity is 80.7%), and it can be confirmed that all five groups are maintained without a large difference in anisotropy regardless of the alternate ratio.

[0062] Meanwhile, Fig. 7 is a drawing showing a comparison of stress distribution and deformation according to alternate ratio when compressing a meniscus scaffold.

[0063] Here, the applied external force was simulated by defining it as 100 N rather than human body load × 2 (1,150 N) because there are no other knee tissues, such as femur cartilage, tibial cartilage, or tibial.

[0064] The simulation results show that the 1:4 group has the smallest stress concentration area for maximum shear stress, compression stress, equivalent stress (Von-Mises stress), and hoop stress, and further shows the smallest deformation.

[0065] Figure 8 is a graph showing the peak stress distribution value and deformation value evaluated and compared according to the alternate ratio when the meniscus scaffold is compressed.

[0066] Referring to Fig. 8, the peak stress and deformation of five groups with different alternate ratios were measured to predict fracture according to load, and the 1:4 group showed mostly low values.

[0067] More specifically, in the 1:4 group, the peak compression stress was measured to be 27.871 MPa, the peak shear stress was 9.7987 MPa, the peak equivalent stress was 17.305 MPa, the peak hoop stress was 3 MPa, and the peak deformation was 0.1303 mm, which are significantly lower values ​​compared to the other groups. This confirms that the structure is most stable when the alternate ratio is approximately 1:4.

[0068] Meanwhile, a biodegradable medical device according to another aspect of the present invention is characterized by including the porous three-dimensional meniscus scaffold of the present invention described above.

[0069] The above medical device may be partially in contact with a living body surface or may be implantable in a living body, and may be used to induce regeneration of surrounding tissues or cells upon contact or implantation. More specifically, the biodegradable medical device may be, but is not limited to, a structure for tissue transplantation, a biomimetic tissue, or the like.

[0070]

[0071] This specification has disclosed preferred embodiments of the present invention, and although specific terms have been used, they are used only in a general sense to easily explain the technical contents of the present invention and to help understand the invention, and are not intended to limit the scope of the present invention. It will be apparent to those skilled in the art that other modifications based on the technical idea of ​​the present invention are possible in addition to the embodiments disclosed herein. For example, those skilled in the art will recognize that the porous three-dimensional meniscus scaffold according to the embodiments can be modified in various ways. Therefore, the scope of the invention should not be defined by the described embodiments, but should be defined by the technical idea described in the claims.

Claims

1. A plurality of first axial layers including one or more first axial fibers formed at a predetermined interval along the first axial direction; and It has a plurality of second axial layers including one or more second axial fibers formed at a predetermined interval along the second axial direction, The first axial layer and the second axial layer are laminated while crossing each other, Among the N+1 (wherein, N is a natural number greater than or equal to 1, and the same applies hereinafter) first axial direction layers, there are any first axial direction fibers (a), any first axial direction fibers (b) that are first adjacent to the first axial direction fibers (a) among the Nth first axial direction layers, and any first axial direction fibers (c) that are second adjacent to the first axial direction fibers (a) among the Nth first axial direction layers. A porous three-dimensional meniscus scaffold, wherein, assuming that the above arbitrary first axial fiber (a) moves vertically (a') to the Nth first axial layer, the ratio between the interval between (a') and (b) and the interval between (a') and (c) is 1:9 to 3:

7.

2. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the first axial fibers and the second axial fibers are laminated in a mutually orthogonal manner.

3. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the above (b), the above (a'), and the above (c) are positioned sequentially from the peripheral side to the central side of the porous three-dimensional meniscus scaffold.

4. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the first axial fibers and the second axial fibers independently comprise at least one polymer selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid (PLA), poly(lactic-co-glycolic) acid (PLGA), polyurethane (PU), and polydioxane.

5. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the width of the pores present inside the porous three-dimensional meniscus scaffold is 1 mm to 2 mm, and the height of the pores is 0.1 to 0.5 mm.

6. In paragraph 1, A porous three-dimensional meniscus scaffold having a porosity of 70% to 85%.

7. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the first axial fibers and the second axial fibers independently have a width of 270 μm to 330 μm.

8. In paragraph 1, A porous three-dimensional meniscus scaffold, wherein the porous three-dimensional meniscus scaffold further comprises circumferential fibers formed to surround its outer surface.

9. In paragraph 1, The above porous three-dimensional meniscus scaffold is a porous three-dimensional meniscus scaffold manufactured using a 3D printer.

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

Images