Composite cartilage scaffold

Abstract

The utility model provides a composite cartilage scaffold. The composite cartilage scaffold comprises a cartilage scaffold layer, a calcification scaffold layer and a subchondral bone scaffold layer which are sequentially stacked and arranged from top to bottom, a plurality of first immersion channels communicated with each other are arranged in the cartilage stent layer and the calcification stent layer, a plurality of first immersion holes are formed in the top of the cartilage stent layer, a plurality of second immersion holes are formed in the side wall of the calcification stent layer, and the first immersion holes and the second immersion holes are communicated with the first immersion channels. Before an operation, the cartilage scaffold layer and the calcification scaffold layer are soaked with cartilage cells, and the cartilage cells are rapidly immersed into the first immersion channel through the first immersion hole and the second immersion hole, so that the cartilage scaffold layer and the calcification scaffold layer can absorb more sufficient cartilage cells, and the cartilage cell content of the scaffold is increased; the secretion of cartilage extracellular matrix is better promoted, the extension of cartilage cells and the coupling between the cartilage cells and in-situ cartilage are facilitated, and the repair of cartilage injury is further promoted.

Description

Technical Field

[0001] The utility model relates to the technical field of medical devices, in particular to a composite cartilage scaffold. Background Art

[0002] With the rapid development of cell biology and tissue engineering, cartilage tissue engineering has made it possible to repair cartilage defects in bones and joints. Cartilage tissue engineering is to combine biological scaffold materials with good biodegradability and tissue compatibility with cartilage seed cells, implant them into cartilage defects, and achieve the purpose of completely repairing cartilage damage. Studies have shown that when chondrocytes are attached to scaffold materials, the repair effect on cartilage damage is better, but because the existing scaffolds carry a low content of chondrocytes, they cannot promote the repair of cartilage damage by chondrocytes. Utility Model Content

[0003] In view of this, the purpose of the utility model is to provide a composite cartilage scaffold to solve the problem that the existing scaffold has a low content of chondrocytes and cannot effectively promote the repair of cartilage damage by chondrocytes.

[0004] Based on the above purpose, the utility model provides a composite cartilage scaffold, comprising: a cartilage scaffold layer, a calcified scaffold layer and a subchondral bone scaffold layer stacked in sequence from top to bottom;

[0005] The cartilage support layer and the calcified support layer are provided with a plurality of first immersion channels connected to each other, the top of the cartilage support layer is provided with a plurality of first immersion holes, the side wall of the calcified support layer is provided with a plurality of second immersion holes, and both the first immersion holes and the second immersion holes are connected to the first immersion channel.

[0006] Optionally, the first immersion channel is in a serpentine shape, and the height of the first immersion channel is in the same direction as the heights of the cartilage support layer and the calcified support layer.

[0007] Optionally, a plurality of second immersion channels that are interconnected are further provided in the cartilage support layer and the calcified support layer, and the plurality of second immersion channels are arranged alternately with the plurality of first immersion channels.

[0008] Optionally, the second immersion channel is serpentine in shape, the height of the second immersion channel is in the same direction as the height of the first immersion channel, the side wall of the second immersion channel is connected to the first immersion channel through a via, and the bottom end of the second immersion channel is connected to the bottom end of the first immersion channel.

[0009] Optionally, the second immersion channel is communicated with the first immersion hole and the second immersion hole respectively.

[0010] Optionally, the cartilage support layer and the calcified support layer are integrated, and the calcified support layer is anchored and connected to the subchondral bone support layer.

[0011] Optionally, at least one anchoring hole for anchoring the calcified support layer is opened at the top of the subchondral bone support layer, and an anchoring column that cooperates with the anchoring hole extends from the side of the calcified support layer that contacts the top of the subchondral bone support layer, and the anchoring column extends into the anchoring hole.

[0012] Optionally, the diameters of the first immersion channel and the second immersion channel are 200 μm-300 μm.

[0013] Optionally, the cartilage scaffold has a diameter of 3 mm to 10 mm and a thickness of 3 mm to 10 mm.

[0014] Optionally, the thickness of the cartilage scaffold layer is 0.6 mm to 2 mm, the thickness of the calcified scaffold layer is 0.6 mm to 2 mm, and the thickness of the subchondral bone scaffold layer is 1.8 mm to 6 mm.

[0015] As can be seen from the above, the composite cartilage scaffold provided by the utility model comprises: a cartilage scaffold layer, a calcified scaffold layer and a subchondral bone scaffold layer stacked in sequence from top to bottom; a plurality of first immersion channels connected to each other are provided in the cartilage scaffold layer and the calcified scaffold layer, a plurality of first immersion holes are provided on the top of the cartilage scaffold layer, a plurality of second immersion holes are provided on the side wall of the calcified scaffold layer, and both the first immersion holes and the second immersion holes are connected to the first immersion channel. Before the operation, the cartilage scaffold layer and the calcified scaffold layer are immersed in chondrocytes, and the chondrocytes are quickly immersed in the first immersion channel through the first immersion holes and the second immersion holes, so that the cartilage scaffold layer and the calcified scaffold layer can absorb more sufficient chondrocytes, increase the chondrocyte content of the scaffold, better promote the secretion of chondrocyte extracellular matrix, which is beneficial to the extension of chondrocytes and the coupling with the in situ cartilage, and further enhance the repair of cartilage damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the present invention or related technologies, the drawings required for use in the embodiments or related technical descriptions are briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0017] Figure 1 This is a schematic diagram of a composite cartilage scaffold structure according to an embodiment of the utility model;

[0018] Figure 2 This is a schematic diagram of the structure of the cartilage support layer and the calcified support layer of an embodiment of the utility model;

[0019] Figure 3 The figure is a schematic diagram of the cross-sectional structure of a composite cartilage scaffold according to an embodiment of the utility model.

[0020] Reference numerals:

[0021] 1. Cartilage scaffold layer; 2. Calcified scaffold layer; 3. Subchondral bone scaffold layer; 10. First immersion hole; 11. First immersion channel; 12. Second immersion channel; 21. Second immersion hole; 22. Anchor column; 31. Anchor hole; 101. Via hole. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

[0023] It should be noted that, unless otherwise defined, the technical terms or scientific terms used in the embodiments of the present invention should be understood by people with ordinary skills in the field to which the present invention belongs. The "first", "second" and similar words used in the embodiments of the present invention do not indicate any order, quantity or importance, but are only used to distinguish different components. "Include" or "comprise" and similar words mean that the elements or objects appearing before the word cover the elements or objects listed after the word and their equivalents, without excluding other elements or objects. "Connect" or "connected" and similar words are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0024] As a framework and temporary substitute for cartilage repair, biological scaffolds can provide a good microenvironment for cell growth in subsequent cartilage repair, and play an important role in the penetration and recruitment, adhesion, growth and reproduction of tissue cells around the cartilage, and the secretion of normal extracellular matrix. In the prior art, the cartilage scaffolds used are mostly single-phase or biphasic scaffolds. The single-phase scaffold is one of the earliest osteochondrocyte repair technologies. It has only one layer of structure and is made of one or more materials. It has the same structure, composition, and mechanical properties. The scaffold has a simple structure and can support the adhesion and growth of osteoblasts and chondrocytes. Due to the unity of the overall structure and composition, the single-phase scaffold lacks the inherent layered structural characteristics required for osteochondrocyte regeneration and repair, and usually does not meet the needs of integrated osteochondrocyte repair. Based on the biocompatibility of the single-phase scaffold, the biphasic scaffold adds a layer of structure and has a two-phase layered structure, and usually each layer has differences in composition, internal structure, and mechanical properties. Compared with single-phase scaffolds, biphasic scaffolds have the characteristics of controllable degradation rate, good cell compatibility, good hydrophilicity, and appropriate biomechanical strength. At the same time, biphasic scaffolds can meet the implantation and repair requirements of cartilage and subchondral bone at the same time. Biphasic scaffolds can be implanted with both osteoblasts and chondrocytes, as well as the same stem cells to construct an osteochondral repair community. Although biphasic scaffolds have significantly improved in simulating natural tissue structures compared to single-phase scaffolds, there may be a problem of poor bonding between the bone and cartilage interface of the constructed tissue.

[0025] Further research has found that the growth microenvironment of cartilage and bone tissue requires different oxygen and nutrient compositions. In the current biphasic scaffold, the cartilage is in direct contact with the subchondral bone, and the chondrocytes and bone cells compete for nutrients and growth environment, which directly affects the differentiation and proliferation of chondrocytes, thereby affecting the repair effect. At present, the bonding between the layers of the biphasic cartilage scaffold is usually done by fibrin glue. This bonding method makes it difficult to tightly bond the two layers of the structure and is easy to separate, affecting the repair effect. At the same time, in the existing biphasic scaffold, only the lower bone phase provides mechanical support for the upper cartilage, and the support capacity is limited. There may be a problem of scaffold collapse, which affects the repair effect.

[0026] Furthermore, the current methods for repairing articular cartilage damage mainly include three types: hyaline cartilage repair, palliative treatment, and restorative treatment. Hyaline cartilage repair can only repair defects with a diameter of less than 3 mm, and its application range is limited; while palliative treatment has limited efficacy and cannot effectively prevent the degeneration of hyaline cartilage; and restorative treatment has problems such as requiring multiple surgeries and slow tissue integration. With the rapid development of cell biology and tissue engineering, cartilage tissue engineering has made it possible to repair osteoarticular cartilage defects. Cartilage tissue engineering is to combine biological scaffold materials with good biodegradability and tissue compatibility with cartilage seed cells, implant them into cartilage defects, and achieve the purpose of completely repairing cartilage damage. Studies have shown that when chondrocytes are attached to the scaffold material, the repair effect on cartilage damage is better, but because the existing scaffold carries a low content of chondrocytes, it cannot promote the repair of cartilage damage by chondrocytes.

[0027] In order to solve some or all of the above technical problems, the utility model provides a composite cartilage scaffold to solve the problems that the existing scaffold has a low chondrocyte content and cannot promote chondrocytes to repair cartilage damage well, as well as the existing poor bonding surface and poor repair effect.

[0028] The composite cartilage scaffold can be prepared according to the following method: (1) constructing a cartilage defect printing model: using MRI to scan the cartilage defect area to obtain a data model of the defect area, drawing the contour of the articular cartilage interface in the mapping software, and using Getdata data software to obtain the screenshot data of the in situ cartilage defect part to form the shape of the target scaffold model, and then refining it into several layers, each layer generates a filling path and superimposed in sequence, while ensuring the aspect ratio, the graphic ratio can be changed to cover the entire printing area; and constructing a first immersion channel 11 connected to each other in the cartilage scaffold layer 1 and the calcified scaffold layer 2, constructing a plurality of first immersion holes 10 on the top of the cartilage scaffold layer 1, and constructing a plurality of second immersion holes 21 on the side wall of the calcified scaffold layer 2, so that the first immersion holes 10 and the second immersion holes 21 are both connected to the first immersion channel 11. (2) Preparation of printing matrix: Silk fibroin is prepared by using silk fibroin and collagen materials, and the cartilage scaffold layer 1 is composed of silk fibroin and collagen; the calcified scaffold layer 2 is composed of collagen materials and hydroxyapatite, and the first immersion channel 11 connected to each other is printed in the cartilage scaffold layer 1 and the calcified scaffold layer 2 by using 3D printing anchoring technology, and a plurality of first immersion holes 10 are printed on the top of the cartilage scaffold layer 1, and a plurality of second immersion holes 21 are printed on the side wall of the calcified scaffold layer 2, so that the first immersion holes 10 and the second immersion holes 21 are connected to the first immersion channel 11. The hydroxyapatite in the calcified scaffold layer 2 has the highest density and naturally precipitates downward during printing, thereby obtaining a three-phase composite cartilage scaffold in which the cartilage scaffold layer 1 and the calcified scaffold layer 2 are integrated. The specific size and shape of the three-phase composite cartilage scaffold are determined according to the specific shape of the defect area. After obtaining the defect data model, the 3D printer directly prints a three-phase composite cartilage scaffold with a shape and size equivalent to the defect area. When the cartilage scaffold layer 1 and the calcified scaffold layer 2 are immersed with chondrocytes, the chondrocytes are quickly immersed into the first immersion channel 11 through the first immersion hole 10 and the second immersion hole 21, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can absorb more sufficient chondrocytes, increase the chondrocyte content of the scaffold, better promote the secretion of chondrocyte extracellular matrix, which is beneficial to the extension of chondrocytes and the coupling with the in situ cartilage, and further enhances the repair of cartilage damage.

[0029] Reference Figures 1 to 3 As shown, the utility model provides a composite cartilage scaffold, comprising: a cartilage scaffold layer 1, a calcified scaffold layer 2 and a subchondral bone scaffold layer 3 which are stacked in sequence from top to bottom;

[0030] The cartilage support layer 1 and the calcified support layer 2 are provided with a plurality of first immersion channels 11 that are interconnected. The top of the cartilage support layer 1 is provided with a plurality of first immersion holes 10. The side wall of the calcified support layer 2 is provided with a plurality of second immersion holes 21. Both the first immersion holes and the second immersion holes are connected to the first immersion channel 11.

[0031] The present embodiment provides a composite cartilage scaffold, wherein the cartilage scaffold layer 1 and the calcified scaffold layer 2 are used to repair cartilage defects, and the subchondral bone scaffold layer 3 provides mechanical support for the cartilage scaffold layer 1. Compared with the prior art, the composite cartilage scaffold has the following beneficial effects:

[0032] (1) A calcified scaffold layer 2 is added. In the existing two-phase scaffold, there is no calcified scaffold layer 2. The cartilage scaffold layer 1 is in direct contact with the subchondral bone scaffold layer 3. The proliferation and differentiation of chondrocytes will be affected by bone cells. The two layers of cells compete for nutrition and space, forming a mutual influence, thus affecting the cartilage repair effect. After adding the calcified scaffold layer 2, the dense calcified scaffold layer 2 divides the osteochondral composite tissue into two different microenvironments, effectively separating chondrocytes and bone cells, providing a good growth environment for the differentiation and proliferation of chondrocytes, avoiding the influence of bone cells on chondrocytes, and effectively improving the cartilage defect repair effect;

[0033] (2) The added calcified scaffold layer 2 can also provide mechanical support to the cartilage scaffold layer 1 to a certain extent. Compared with the prior art in which only the subchondral bone scaffold layer 3 provides mechanical support, the mechanical strength is improved, the formation of collapse of the defect area is effectively avoided, and the cartilage repair effect is further improved;

[0034] (3) The cartilage scaffold layer 1 and the calcified scaffold layer 2 are provided with a plurality of first immersion channels 11 that are interconnected. The top of the cartilage scaffold layer 1 is provided with a plurality of first immersion holes 10. The side wall of the calcified scaffold layer 2 is provided with a plurality of second immersion holes 21. The first immersion holes 10 and the second immersion holes 21 are both connected to the first immersion channel 11. When the cartilage scaffold layer 1 and the calcified scaffold layer 2 are immersed in chondrocytes, the chondrocytes are quickly immersed in the first immersion channel 11 through the first immersion holes 10 and the second immersion holes 21, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can absorb more sufficient chondrocytes, increase the chondrocyte content of the scaffold, better promote the secretion of chondrocyte extracellular matrix, facilitate the extension of chondrocytes and the coupling with the original cartilage, and further enhance the repair of cartilage damage.

[0035] In some embodiments, Figure 2 and Figure 3 As shown, the first immersion channel 11 is in a serpentine shape, and the height of the first immersion channel 11 is in the same direction as the heights of the cartilage support layer 1 and the calcified support layer 2 .

[0036] Specifically, the first channel is set through the cartilage support layer 1 and the calcified support layer 2, and the multiple first immersion channels 11 can be arranged in an equidistant array or in a staggered arrangement. The utility model takes the arrangement of multiple first immersion channels 11 in an equidistant array as an example. The first immersion channel 11 is set in a serpentine shape, and the height of the serpentine shape is in the same direction as the height of the cartilage support layer 1 and the calcified support layer 2; in this way, chondrocytes can smoothly immerse into the interior of the cartilage support layer 1 and the calcified support layer 2 through the serpentine-shaped first immersion channel 11, so that the cartilage support layer 1 and the calcified support layer 2 are immersed in more chondrocytes, thereby increasing the chondrocyte content of the support, better promoting the secretion of chondrocyte extracellular matrix, facilitating the extension of chondrocytes and coupling with the in situ cartilage, and further improving the repair of cartilage damage.

[0037] In some embodiments, Figure 2 As shown, the cartilage support layer 1 and the calcified support layer 2 are further provided with a plurality of second immersion channels 12 that are interconnected, and the plurality of second immersion channels 12 are alternately arranged with the plurality of first immersion channels 11 .

[0038] Specifically, the cartilage scaffold layer 1 and the calcified scaffold layer 2 are further provided with a plurality of interconnected second immersion channels 12, and the plurality of second immersion channels 12 are arranged in an array at equal distances, and each second immersion channel 12 is staggered with all the first immersion channels 11, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can absorb more chondrocytes, thereby increasing the chondrocyte content of the scaffold, better promoting the secretion of chondrocyte extracellular matrix, facilitating the extension of chondrocytes and coupling with the in situ cartilage, and further enhancing the repair of cartilage damage.

[0039] In some embodiments, Figure 2 and Figure 3 As shown, the second immersion channel 12 is in a serpentine shape, the height of the second immersion channel 12 is in the same direction as the height of the first immersion channel 11, the side wall of the second immersion channel 12 is connected to the first immersion channel 11 through the via 101, and the bottom end of the second immersion channel 12 is connected to the bottom end of the first immersion channel 11.

[0040] Specifically, the second immersion channel 12 is serpentine in shape, and the height of the second immersion channel is in the same direction as the height of the first immersion channel 11; since the second immersion channel 12 is staggered with all the first immersion channels 11, the side walls of the second immersion channels 12 are connected to the side walls of the first immersion channels 11 through the vias 101, so that all the second immersion channels 12 can be connected to the first immersion channels 11, and the bottom ends of the second immersion channels 12 can be connected to the bottom ends of the first immersion channels 11 (the bottom ends can be connected through vias, or the connection between the second immersion channels 12 and the first immersion channels 11 can be directly opened, which is arranged according to actual conditions and is not specifically limited in the utility model), thereby increasing the porosity of the cartilage scaffold layer 1 and the calcified scaffold layer 2, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can be better absorbed by cartilage cells.

[0041] In some embodiments, Figure 3 As shown, the second immersion channel 12 is communicated with the first immersion hole 10 and the second immersion hole 21 respectively.

[0042] Specifically, the side walls at both ends of the second immersion channel are connected to the second immersion hole 21, and the top of the second immersion channel 12 is connected to each first immersion hole 10, so that the second immersion channel 12 is connected to both the first immersion hole 10 and the second immersion hole 21, increasing the porosity of the cartilage scaffold layer 1 and the calcified scaffold layer 2, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can be better absorbed by chondrocytes. And the pore structure can further affect the cell response during the cartilage defect repair process, regulate cell invasion, angiogenesis, tissue regeneration and other processes. Therefore, the existence of the channel allows the growth of chondrocytes to have an extension space, realizes the coupling between the extension of chondrocytes and the in situ cartilage, and further improves the repair effect.

[0043] In some embodiments, the cartilage support layer 1 and the calcified support layer 2 are integrated, and the calcified support layer 2 is anchored and connected to the subchondral bone support layer 3 .

[0044] Specifically, the cartilage support layer 1 and the calcified support layer 2 are integrated, and the calcified support layer 2 and the subchondral bone support layer 3 are anchored, replacing the fibrin glue bonding method in the prior art, effectively reinforcing the combination of the cartilage support layer 1, the calcified support layer 2 and the subchondral bone support layer 3, and effectively avoiding the separation of the bonding surface. With the addition of the calcified support layer 2 and the application of the anchoring technology, the combination of the bone and cartilage interface and the cartilage defect repair effect can be greatly improved.

[0045] In some embodiments, the calcified scaffold layer 2 is a hydroxyapatite layer. The hydroxyapatite layer is mainly composed of hydroxyapatite and type II collagen. Hydroxyapatite contains calcium and phosphorus elements necessary for human tissue. After implantation in the body, it can participate in the body's metabolism and be absorbed by the tissue. It has good biocompatibility and osteoconduction, can guide bone growth, and form a firm bone bond with bone tissue, improve the bonding of the bone cartilage interface, and improve the repair effect. At the same time, the cartilage scaffold layer 1 is mainly composed of silk fibroin and type II collagen. The cartilage scaffold layer 1 and the calcified scaffold layer 2 contain the same collagen material, which can improve the biocompatibility of the cartilage scaffold layer 1 and the calcified scaffold layer 2, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 are better combined, ensuring the integrated bonding structure of the cartilage scaffold layer 1 and the calcified scaffold layer 2.

[0046] In some embodiments, at least one anchoring hole 31 for anchoring the calcified support layer 2 is opened at the top of the subchondral bone support layer 3, and an anchoring column 22 that cooperates with the anchoring hole 31 extends from the side of the calcified support layer 2 that contacts the top of the subchondral bone support layer 3, and the anchoring column 22 extends into the anchoring hole 31.

[0047] Specifically, the material and components of the anchoring column 22 are the same as those of the calcified support layer 2. The number of anchoring holes 31 and anchoring columns 22 is set according to the diameter of the support, at least one is set, and if the diameter is large, multiple can be set; the anchoring column 22 and the anchoring hole 31 can be set obliquely or vertically; through 3D printing technology, the calcified support layer 2 and the cartilage support layer 1 are integrally printed on the subchondral bone support layer 3, and the anchoring column 22 is placed in the anchoring hole 31. The calcified support layer 2 is anchored in the anchoring hole 31 through the mutual cooperation of the anchoring column 22 and the anchoring hole 31, so as to realize the anchoring of the cartilage support layer 1, the calcified support layer 2 and the subchondral bone support layer 3. The bonding surface using anchoring connection has a better bonding strength than that using fibrin glue. In cartilage repair, the separation of the bonding surface can be effectively avoided and the repair effect can be improved.

[0048] In some embodiments, the subchondral bone support layer 3 is allogenic pressure trabeculae. The allogenic femoral head contains allogenic pressure trabeculae and allogenic tension trabeculae, and the specific difference is that the forces they bear and the directions of arrangement are different. The allogenic pressure trabeculae are arranged in the direction of pressure, and the allogenic tension trabeculae are arranged in the direction of tension. The pressure-bearing capacity of allogenic pressure trabeculae is better than that of allogenic tension trabeculae. In the repair of cartilage defects, the subchondral bone support layer 3 needs to provide mechanical support to the cartilage support layer 1, and the subchondral bone support layer 3 needs to have a certain pressure-bearing capacity. Therefore, the selection of allogenic pressure trabeculae as the subchondral bone support layer 3 can well support the cartilage support layer 1, and avoid internal collapse during the repair process due to insufficient pressure-bearing capacity of the subchondral bone support layer 3, which affects the repair of cartilage damage.

[0049] In some embodiments, the subchondral bone support layer 3 is allogenic pressure trabeculae. The allogenic femoral head contains allogenic pressure trabeculae and allogenic tension trabeculae, and the specific difference is that the forces they bear and the directions of arrangement are different. The allogenic pressure trabeculae are arranged in the direction of pressure, and the allogenic tension trabeculae are arranged in the direction of tension. The pressure-bearing capacity of allogenic pressure trabeculae is better than that of allogenic tension trabeculae. In the repair of cartilage defects, the subchondral bone support layer 3 needs to provide mechanical support to the cartilage support layer 1, and the subchondral bone support layer 3 needs to have a certain pressure-bearing capacity. Therefore, the selection of allogenic pressure trabeculae as the subchondral bone support layer 3 can well support the cartilage support layer 1, and avoid internal collapse during the repair process due to insufficient pressure-bearing capacity of the subchondral bone support layer 3, which affects the repair of cartilage damage.

[0050] In some embodiments, the diameters of the first immersion channel 11 and the second immersion channel 12 are 200 μm-300 μm.

[0051] Specifically, the purpose of setting up the channel is to provide extension space for the growth of chondrocytes. When the channel diameter is comparable to the chondrocyte diameter, the chondrocytes can extend better in the channel. The diameter of chondrocytes is about 100μm to 150μm. Therefore, when the diameter of the immersion channel is set to 200μm to 300μm, the chondrocytes can extend well in the channel, further ensuring the coupling between the extension of chondrocytes and the in situ cartilage.

[0052] In some embodiments, the cartilage scaffold is cylindrical. According to tests, the cylindrical shape has better pressure distribution and stress distribution than other shapes such as rectangle and oblique shape. When repairing cartilage defects, the cartilage defect area needs to be trimmed first. Compared with trimming into rectangle and oblique shape, it is easier to trim into a cylindrical shape. At the same time, most of the clinical work is also trimmed into a cylindrical shape. Therefore, designing the cartilage scaffold into a cylindrical shape has better force and stress distribution, and is more in line with the actual needs of current clinical practice.

[0053] In some embodiments, the cartilage scaffold has a diameter of 3 mm to 10 mm and a thickness of 3 mm to 10 mm.

[0054] Specifically, in clinical applications, the diameter and thickness of the three-phase composite cartilage scaffold are determined according to the specific cartilage defect area. The diameter can be 3mm, 4mm, 5mm, 5.5mm, 6mm, 7mm, 7.5mm, 8mm, 9mm, 10mm, 11mm, etc. The thickness of the scaffold can be 3mm, 4mm, 5mm, 5.5mm, 6mm, 7mm, 7.5mm, 8mm, 9mm, 10mm, 11mm, etc. For defect areas with a diameter and defect depth exceeding 10mm, a certain degree of repair can also be performed. Normally, the diameter of the cartilage defect area of ​​the human body is 3mm to 10mm, and the scaffold used for repairing cartilage defects in the human body is generally 10mm thick. However, the utility model can be applied not only to human cartilage repair, but also to animal cartilage repair. The cartilage scaffold used in animals is usually smaller than the cartilage scaffold used in humans. Under normal circumstances, the thickness is generally 3mm to 10mm. The repair effect within this period is better, and it can also be repaired to a certain extent if it exceeds this interval.

[0055] In some embodiments, the thickness of the cartilage scaffold layer 1 is 0.6 mm to 2 mm, the thickness of the calcified scaffold layer 2 is 0.6 mm to 2 mm, and the thickness of the subchondral bone scaffold layer 3 is 1.8 mm to 6 mm.

[0056] In clinical applications, the thickness of each layer of the three-phase composite cartilage scaffold is determined according to the specific bone layer structure of the implanted host. The thickness of the cartilage scaffold layer 1 can be 0.6mm, 0.8mm, 1mm, 1.3mm, 1.5mm, 1.7mm, 1.9mm, 2mm, 3mm, etc., the thickness of the calcified scaffold layer 2 can be 0.6mm, 0.8mm, 1mm, 1.3mm, 1.5mm, 1.7mm, 1.9mm, 2mm, 3mm, etc., and the thickness of the subchondral bone scaffold layer 3 can be 1.8mm, 1.9mm, 2mm, 2.2mm, 2.5mm, 3mm, 3.8mm, 4mm, 5mm, 6mm, 7mm. The thickness of the cartilage scaffold layer 1 and the calcified scaffold layer 2 of the human body is about 2mm. When the thickness distribution of each layer of the scaffold is comparable to the thickness of each layer of the cartilage structure of the implanted host, a better repair effect can be achieved. The thickness of the subchondral bone scaffold layer 3 is significantly thicker than that of the cartilage scaffold layer 1, and can provide good mechanical support for the cartilage scaffold layer 1 in the subsequent repair process. When applied to animal cartilage repair, the thickness varies with the specific bone layer structure of the host. The cartilage scaffold layer 1 and the calcified scaffold layer 2 are generally in the range of 0.6mm to 2mm, and the subchondral bone scaffold layer 3 is generally in the range of 1.8mm to 6mm. The repair effect within this period is better, and those exceeding this range can also be repaired to a certain extent.

[0057] New Zealand rabbits were selected for cartilage defect repair experiments, and the area around the cartilage defect was trimmed and shaped to establish a tissue engineering model for articular cartilage defect repair. MRI scanning was used to locate the whole knee joint sequence to obtain proton density weighted imaging, and the shape of the target scaffold model was drawn using software, and the composite cartilage scaffold of the utility model was obtained by 3D printing. New Zealand rabbits were selected as experimental subjects and divided into three groups: a three-phase scaffold group, a two-phase scaffold group (silk collagen cartilage layer + subchondral bone layer) and a blank control group. The three-phase and two-phase composite cartilage scaffolds were implanted into the New Zealand rabbits in the three-phase scaffold group and the two-phase scaffold group, respectively. The three-phase scaffold group and the two-phase scaffold group were raised freely under a mechanical environment; the blank control group did not implant the scaffold in its joint defect. The cartilage defect repair of the three-phase scaffold group, the two-phase scaffold group and the blank control group was observed at 2, 4 and 8 weeks after surgery. The joints of the New Zealand rabbits in the three-phase scaffold group and the two-phase scaffold group had been significantly repaired in the second week, while the joints of the New Zealand rabbits in the blank control group were not effectively repaired. In the 4th week, the repair of the joints of the New Zealand rabbits in the three-phase scaffold group was more obvious, and the two-phase scaffold group began to collapse; in the 8th week, the cartilage defect area in the three-phase scaffold group had been basically repaired, and the defect was difficult to see with the naked eye, while the cartilage layer in the two-phase scaffold group completely collapsed, and a defect area appeared; in the New Zealand rabbits in the blank control group, the repair effect was limited, and the defect could be clearly seen with the naked eye. Experiments have shown that after the cartilage scaffold of the utility model is implanted, it can effectively accelerate the healing of cartilage and improve the repair effect.

[0058] Compared with the prior art, the utility model provides a cartilage scaffold with better repair effect. By adding a calcified scaffold layer 2, the growth microenvironment of cartilage and bone tissue is effectively isolated, the influence of bone cells on the proliferation and differentiation of chondrocytes is avoided, the cartilage, calcified cartilage and subchondral bone are reconstructed, and the integration of osteochondral repair is realized; the anchoring technology is adopted to anchor the calcified scaffold layer 2 and the subchondral bone scaffold layer 3 to increase the tightness of the connection. At the same time, the subchondral bone scaffold layer 3 can provide mechanical support for the cartilage scaffold layer 1, avoid the formation of collapse, improve the combination of the bone cartilage interface, and improve the repair effect; the cartilage scaffold layer 1 and the calcified scaffold layer 2 are provided with a plurality of first immersion channels 11 which are connected to each other The top of the cartilage scaffold layer 1 is provided with a plurality of first immersion holes 10, and the side wall of the calcified scaffold layer 2 is provided with a plurality of second immersion holes 21. The first immersion holes 10 and the second immersion holes 21 are both connected to the first immersion channel 11. When the cartilage scaffold layer 1 and the calcified scaffold layer 2 are immersed in chondrocytes, the chondrocytes quickly immerse into the first immersion channel 11 through the first immersion holes 10 and the second immersion holes 21, so that the cartilage scaffold layer 1 and the calcified scaffold layer 2 can absorb more sufficient chondrocytes, increase the chondrocyte content of the scaffold, better promote the secretion of chondrocyte extracellular matrix, and facilitate the extension of chondrocytes and the coupling with the original cartilage, and further improve the repair of cartilage damage. At the same time, it provides an extension space for the growth of chondrocytes, further facilitates the extension of chondrocytes and the coupling with the original cartilage, and further improves the repair effect; it is suitable for repairing defects of various degrees, and is effectively suitable for defects with a diameter of 3mm or even more than 10mm.

[0059] It should be noted that some embodiments of the utility model are described above. Other embodiments are within the scope of the appended claims. In some cases, the actions or steps recorded in the claims can be performed in an order different from that in the above embodiments and still achieve the desired results. In addition, the processes depicted in the accompanying drawings do not necessarily require the specific order or continuous order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0060] Although the present invention has been described in conjunction with specific embodiments of the present invention, many replacements, modifications and variations of these embodiments will be apparent to those skilled in the art based on the foregoing description. For example, other memory architectures may use the discussed embodiments.

[0061] The embodiments of the present invention are intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the embodiments of the present invention should be included in the scope of protection of the present invention.

Claims

1. A composite cartilage scaffold, characterized in that: include: A cartilage scaffold layer (1), a calcified scaffold layer (2) and a subchondral bone scaffold layer (3) are sequentially stacked from top to bottom; The cartilage support layer (1) and the calcified support layer (2) are provided with a plurality of first immersion channels (11) that are interconnected, the top of the cartilage support layer (1) is provided with a plurality of first immersion holes (10), and the side wall of the calcified support layer (2) is provided with a plurality of second immersion holes (21), and both the first immersion holes and the second immersion holes are connected to the first immersion channel (11).

2. The composite cartilage scaffold according to claim 1, characterized in that: The first immersion channel (11) is in a serpentine shape, and the height of the first immersion channel (11) is in the same direction as the heights of the cartilage scaffold layer (1) and the calcified scaffold layer (2).

3. The composite cartilage scaffold according to claim 2, characterized in that: The cartilage support layer (1) and the calcified support layer (2) are also provided with a plurality of second immersion channels (12) that are interconnected, and the plurality of second immersion channels (12) and the plurality of first immersion channels (11) are arranged in an alternating manner.

4. The composite cartilage scaffold according to claim 3, characterized in that: The second immersion channel (12) is in a serpentine shape, the height of the second immersion channel (12) is in the same direction as the height of the first immersion channel (11), the side wall of the second immersion channel (12) is connected to the first immersion channel (11) through a via (101), and the bottom end of the second immersion channel (12) is connected to the bottom end of the first immersion channel (11).

5. The composite cartilage scaffold according to claim 4, characterized in that: The second immersion channel (12) is communicated with the first immersion hole (10) and the second immersion hole (21) respectively.

6. The composite cartilage scaffold according to claim 1, characterized in that: The cartilage support layer (1) and the calcified support layer (2) are integrated into one body, and the calcified support layer (2) and the subchondral bone support layer (3) are anchored and connected.

7. The composite cartilage scaffold according to claim 1, characterized in that: At least one anchoring hole (31) for anchoring the calcified support layer (2) is formed at the top of the subchondral bone support layer (3); an anchoring column (22) that cooperates with the anchoring hole (31) extends from the side of the calcified support layer (2) that contacts the top of the subchondral bone support layer (3); and the anchoring column (22) extends into the anchoring hole (31).

8. The composite cartilage scaffold according to claim 3, characterized in that: The diameters of the first immersion channel (11) and the second immersion channel (12) are 200 μm-300 μm.

9. The composite cartilage scaffold according to claim 1, characterized in that: The cartilage scaffold has a diameter of 3 mm to 10 mm and a thickness of 3 mm to 10 mm.

10. The composite cartilage scaffold according to claim 1, characterized in that: The thickness of the cartilage support layer (1) is 0.6 mm to 2 mm, the thickness of the calcified support layer (2) is 0.6 mm to 2 mm, and the thickness of the subchondral bone support layer (3) is 1.8 mm to 6 mm.

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