Micro-nano robot for repairing cartilage injury and preparation method

Abstract

The invention discloses a cartilage repair stent, a preparation method thereof and a cartilage repair stent combination, and belongs to the technical field of medical instruments. The cartilage repair stent comprises a stent body, and the materials of the stent body comprise a photoresist, a magnetic material and a photocuring biocompatible material; the stent body is a hollow structural body with a porous structure. The preparation method of the cartilage repair scaffold comprises the following steps: mixing photoresist, a magnetic material and a photocuring biocompatible material to obtain a mixed material; the mixed material is printed in a 3D printing mode, and the stent body is obtained. The cartilage repair stent disclosed by the invention has good biocompatibility and biomechanical property, can be injected and is high in clinical practicability.

Description

Technical Field

[0001] The present application belongs to the field of medical device technology, and specifically relates to a cartilage repair scaffold, a preparation method thereof, and a cartilage repair scaffold combination. Background Art

[0002] There are more and more patients suffering from articular cartilage injuries, and the incidence of articular cartilage injuries is as high as about 63%. The self-repair ability after injury is limited. That is, because cartilage tissue has no blood supply and nerve innervation, and the low metabolic activity of chondrocytes and the high-density extracellular matrix limit the migration of chondrocytes to the defect area, the self-repair ability after damage is limited. Therefore, cartilage tissue engineering has great application prospects in cartilage repair.

[0003] In recent years, early repair of damaged cartilage and blocking the occurrence of osteoarthritis have been challenging problems in the medical field at home and abroad. Both conservative treatment and traditional surgical treatment have their shortcomings. Tissue engineering technology has a good application prospect in cartilage damage repair. However, in clinical practice, this method still requires opening the joint or placing a cartilage scaffold with the assistance of arthroscopic surgery, causing iatrogenic trauma; that is, most of the current traditional porous scaffolds cannot be transplanted in vivo by simple injection, and still need to be implanted through traditional surgical methods that are more traumatic. Injectable biological scaffolds are easy to use and can effectively and fully fill tissue defects, and have great clinical application prospects. In addition, the biocompatibility and biomechanical properties of cartilage scaffold materials are also issues that need to be urgently addressed. Summary of the invention

[0004] In view of the above problems, the present invention aims to solve one of the technical problems in the related art to at least a certain extent. To this end, the present invention provides a cartilage repair scaffold and a preparation method thereof and a cartilage repair scaffold combination, which has good biocompatibility and biomechanical properties, is injectable, and has strong clinical practicality.

[0005] In order to solve the above technical problems, this application is implemented as follows:

[0006] According to one aspect of the present application, an embodiment of the present application provides a cartilage repair scaffold, the cartilage repair scaffold comprising a scaffold body, the material of the scaffold body comprising photoresist, magnetic material and photocurable biocompatible material;

[0007] The support body is a hollow structure with a porous structure.

[0008] In some embodiments, the porosity of the stent body is 60% to 80%.

[0009] In some embodiments, the pore size of the porous structure is 5 μm to 25 μm.

[0010] In some of the embodiments, the bracket body is a cubic structure with a hollow structure, a first hole is provided in the middle of the side of the cubic structure, a prism wall is provided around the first hole, and a plurality of second holes are distributed on the prism wall; the length of the prism wall is 100 μm to 500 μm, and the width of the prism wall is 10 μm to 50 μm.

[0011] In some embodiments, the mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material is 1:5-15:20-40.

[0012] In some of the embodiments, the photoresist includes IP-photoresist (IP series photoresist).

[0013] In some embodiments, the magnetic material includes ferrosoferric oxide.

[0014] In some embodiments, the photocurable biocompatible material comprises methacrylated polycaprolactone.

[0015] In some embodiments, the scaffold body is loaded with cartilage-derived stem cells.

[0016] According to another aspect of the present application, the present application embodiment also provides a method for preparing the cartilage repair scaffold as described above, characterized in that it comprises the following steps:

[0017] mixing a photoresist, a magnetic material and a photocurable biocompatible material to obtain a mixed material;

[0018] The mixed material is printed by 3D printing to obtain a stent body.

[0019] In some embodiments, the method further comprises: inoculating cartilage-derived stem cells in the scaffold body and culturing them in a culture medium; the culture medium comprises DMEM culture medium, F12 culture medium or a mixed culture medium consisting of DMEM culture medium and F12 culture medium.

[0020] According to another aspect of the present application, an embodiment of the present application also provides a cartilage repair scaffold combination, which includes a plurality of cartilage repair scaffolds as described above or cartilage repair scaffolds prepared by the aforementioned method; wherein the plurality of scaffold bodies interact with each other to produce cross-links to form the cartilage scaffold combination.

[0021] In some embodiments, in the cartilage repair scaffold combination, the porous structures in the plurality of scaffold bodies form interconnected pore structures.

[0022] In some embodiments, the plurality of stents are subjected to secondary curing under ultrasound to generate cross-linking, and the curing temperature is 38° C. to 42° C.

[0023] Implementing the technical solution of the present invention has at least the following beneficial effects:

[0024] In the embodiment of the present application, the provided cartilage repair scaffold includes a scaffold body, the material of the scaffold body includes photoresist, magnetic material and photocurable biocompatible material; and the scaffold body is a hollow structure with a porous structure. Thus, the photoresist used is a photocurable material, which has biocompatibility and can be used for 3D printing of various conventional or complex micro-scaffolds. The photocurable biocompatible material is a photocurable and biodegradable material, which meets the mechanical strength and biocompatibility of the cartilage scaffold. The magnetic material can provide magnetic control performance, and then through the synergistic cooperation of the above-mentioned photoresist, magnetic material and photocurable biocompatible material, it is conducive to meeting the current requirements of biocompatibility and biomechanical properties of cartilage scaffold materials. In addition, the provided cartilage repair scaffold can be injected into the joint through a fine needle, etc., and then the scaffold can be accurately displaced to the cartilage defect area under the control of an external magnetic field. It can also enable multiple scaffold bodies to be cross-linked and cured to form a cartilage repair scaffold combination. Further, the cartilage-derived stem cells carried by the cartilage repair scaffold can obtain nutrition and proliferation through the pore structure of the scaffold to complete the in situ regeneration of cartilage.

[0025] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the structure of the cartilage repair scaffold provided for some exemplary embodiments of the present application.

[0027] Figure 2 A schematic diagram of the structure of a cartilage repair scaffold assembly provided for some exemplary embodiments of the present application.

[0028] Figure 3 Confocal images of cartilage-derived stem cells on cartilage repair scaffolds provided for this application (Note: Figure 3 Green represents actin and blue represents cell nuclei).

[0029] Figure 4 Micro-CT (micro-CT) and pathological results of in situ cartilage regeneration of cartilage repair scaffolds are provided for this application.

[0030] Description of reference numerals:

[0031] 10-Cartilage repair scaffold;

[0032] 110- bracket body; 111- porous structure; 1111- first hole; 1112- second hole; 112- edge wall;

[0033] 120-cartilage-derived stem cells;

[0034] 20-Cartilage repair scaffold combination;

[0035] 201-Pore structure. DETAILED DESCRIPTION

[0036] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0037] As analyzed in the background technology, the existing cartilage repair scaffolds still have more or less defects, and there is still a need for improvement. For example, most of the current traditional porous scaffolds cannot be transplanted in vivo by simple injection. It is still necessary to open the joint or place the cartilage scaffold under the assistance of arthroscopic surgery, which is easy to cause iatrogenic trauma. In addition, the current traditional porous scaffolds have a large physical size, which will cause certain obstacles to the entry of nutrients and cells into the scaffold, affecting the survival and proliferation of cells on the scaffold. In addition, the biocompatibility and biomechanical properties of existing cartilage scaffold materials still need to be further improved.

[0038] In view of this, the technical solution of the embodiment of the present application provides a cartilage repair scaffold and a preparation method thereof and a cartilage repair scaffold combination, by constructing a multifunctional integrated controllable cartilage injury repair micro-nano robot (cartilage repair scaffold), to achieve minimally invasive and intelligent cartilage injury repair, and can alleviate the above-mentioned technical problems. The specific technical solution is described below.

[0039] See also Figure 1 As shown, in some embodiments of the present application, a cartilage repair scaffold 10 is provided, which includes a scaffold body 110, and the material of the scaffold body 110 includes photoresist, magnetic material and photocurable biocompatible material; the scaffold body 110 is a hollow structure with a porous structure 111.

[0040] The stent body 110 of the cartilage repair stent 10 of the embodiment of the present application has a hollow structure, and the stent body 110 has a porous structure 111, so that the stent body has a three-dimensional porous structure with a high connectivity rate. Compared with the existing (millimeter-level) stents, the stent body of this embodiment has a smaller physical size, which is conducive to the entry of nutrients, the growth of cells and tissues, and can promote cell adhesion and proliferation.

[0041] The material of the support body 110 of the cartilage repair support 10 of the embodiment of the present application includes photoresist, magnetic material and photocurable biocompatible material, that is, the support body 110 can be mainly made of photoresist, magnetic material and photocurable biocompatible material. In this way, through the coordinated cooperation of photoresist, magnetic material and photocurable biocompatible material, it is conducive to meeting the current requirements of biocompatibility and biomechanical properties of cartilage support materials. Among them, photoresist belongs to photocurable material, has biocompatibility, and meets the relevant requirements of biocompatibility detection of medical devices, and can be used for 3D printing of various conventional or complex micro-supports, such as can be used to print extremely complex 3D micro-supports. Magnetic materials can be used to provide magnetic control performance, such as, after the support is injected into the joint, through the setting of the magnetic material, the group regulation displacement to the cartilage defect area can be achieved under the control of the external magnetic field. The photocurable biocompatible material is a photocurable and biodegradable material, which meets the mechanical strength and biocompatibility of the cartilage support, and can meet the current requirements of biocompatibility and biomechanical properties of the cartilage support material.

[0042] Compared with the existing in vivo application method of the stent, it is necessary to use open surgery and other techniques to implant the stent material into the body, which is more traumatic and more expensive. In the present application, the cartilage repair stent 10 provided is of small size and structure, can be injected into the joint, and the material of the stent body 110 contains magnetic material, which can realize the precise displacement of the stent to the cartilage defect area under the control of the external magnetic field, and can also make multiple stent bodies 110 undergo secondary cross-linking and curing to form a cartilage repair stent assembly 20, such as, at a certain temperature, the light-cured biocompatible material in the stent body 110 can produce cross-linking due to the increase in temperature, its hydrogen bonds and hydrophobic interactions, forming a cross-linked network structure, and then realizing the cross-linking of the stent body and curing and residing in the cartilage defect area; further, the cartilage-derived stem cells carried by the cartilage repair stent can obtain nutrition and proliferation through the pore structure of the stent to complete the in situ regeneration of cartilage. Thus, the cartilage repair stent is simple and reliable to use, simple and convenient to operate, and is very suitable for the application of clinical cartilage damage repair, which improves clinical applicability.

[0043] In the present application, the provided cartilage repair scaffold (cartilage injury repair scaffold) can provide a mechanical support structure for the growth of chondrocytes and also has a pore structure that is conducive to the nutrient penetration of cell growth.

[0044] In the present application, the provided cartilage repair scaffold can be gradually degraded as the cartilage is repaired.

[0045] In some embodiments, the photoresist includes but is not limited to IP-photoresist; further, the photoresist includes IP-Visio photoresist, that is, the photoresist can be an IP series photoresist, especially IP-Visio photoresist. IP-Visio photoresist has the characteristics of non-biotoxicity and can be used to make high-precision 3D microstructures, meeting the different requirements of life science application fields. IP-Visio photoresist meets ISO 10993-5 / USP87 requirements, has biocompatibility, and can be applied to biocompatible three-dimensional scaffolds, such as printing extremely complex 3D microscaffolds. In addition, the protein adsorption resin polyacrylic acid contained in IP-Visio photoresist can increase the adhesion performance of cartilage-derived stem cells 120.

[0046] It should be noted that the IP-Visio photoresist in this application is a material known in the prior art, which can be obtained commercially. For example, the IP-Visio photoresist can be sourced from Nanoscribe GmbH (German Nanoscribe, founded in 2007, headquartered in Karlsruhe, Germany). This application mainly utilizes the protein adsorption resin polyacrylic acid contained in IP-Visio photoresist to increase the adhesion performance of cartilage-derived stem cells, and there is no restriction on the source of the IP-Visio photoresist.

[0047] In the present application, by making the preparation material of the stent body 110 include IP-Visio photoresist, the surface of the stent body 110 can be made more conducive to cell adhesion and growth and have good cell compatibility.

[0048] In some embodiments, the magnetic material includes but is not limited to ferrosoferric oxide (Fe3O4).

[0049] In the present application, the magnetic material may be ferrosoferric oxide, which can be used to provide magnetic control properties, so that when the cartilage repair scaffold 10 is injected into the joint, it can achieve group-controlled displacement to the cartilage defect area under the control of an external magnetic field.

[0050] It should be pointed out that the embodiments of the present application do not limit the specific operation method or structure of the external magnetic field control, and reference may be made to the relevant prior art, which will not be described in detail here.

[0051] As an example, when the cartilage repair scaffold 10 is injected into the joint, the group is controlled and moved to the cartilage defect area under the control of the external magnetic field. The magnetic field is an EMA magnetic control system, which can be composed of 6 electromagnetic coils. By adjusting the coil current, a maximum field strength of 100mT and 1.5Tm can be generated in the working space. -1The gradient magnetic field can directionally control the movement trajectory of the cartilage repair stent 10 by changing the field strength.

[0052] In some embodiments, the photocurable biocompatible material includes, but is not limited to, polycaprolactone methacrylate (PCLMA).

[0053] In the present application, the photocurable biocompatible material may be polymethacryloyl caprolactone (PCLMA), which is an organic polymer material that is photocurable and biodegradable, and meets the mechanical strength and biocompatibility requirements of cartilage scaffolds. In particular, it has good mechanical strength properties and can be used to provide good mechanical support, that is, it can be used to provide a mechanical support structure for the growth of chondrocytes.

[0054] It should be noted that the source of the methacryloyl polycaprolactone is not particularly limited in this embodiment. For example, it can be purchased from the market, or it can be prepared by itself according to methods known in the art.

[0055] As an example, the preparation of methacryloyl polycaprolactone (PCLMA) may include: first, synthesizing a three-arm hydroxy-terminated PCL oligomer by a ring-opening polymerization method, then adding methacrylic anhydride (MAAh) and triethylamine (TEA), completing the methacryloylation of PCL under an argon atmosphere at room temperature, and after the reaction is completed, removing excess MAAh and TEA in the coupling reaction by precipitating the macromolecule in cold isopropanol to obtain PCLMA.

[0056] In some embodiments, the mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material is 1:5-15:20-40. Preferably, the mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material is 1:8-12:25-35. More preferably, the mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material is 1:10:30.

[0057] The mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material can be selectively adjusted according to the actual application. For example, the mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material can be 1:5:20, 1:6:22, 1:7:23, 1:8:25, 1:9:28, 1:10:30, 1:12:32, 1:15:40, etc.

[0058] By controlling the mass ratio of magnetic material, photoresist and photocurable biocompatible material within the above range, it is helpful to fully exert the performance of each material and effectively exert the synergistic effect of the three to produce a cartilage repair scaffold with excellent performance.

[0059] In the present application, after the magnetic material, the photoresist and the photocurable biocompatible material are mixed in the above-mentioned appropriate mass ratio, they can be printed by 3D printing technology to obtain the stent body 110 .

[0060] In some embodiments, the porosity of the stent body 110 is 60% to 80%. Preferably, the porosity of the stent body 110 is 70% to 80%. More preferably, the porosity of the stent body 110 is 75%. As an example, the porosity of the stent body 110 can be 60%, 62%, 65%, 68%, 70%, 72%, 74%, 75%, 76%, 78%, 80%, or a range of any two values.

[0061] By making the porosity of the support body 110 within the above-mentioned suitable range, the support body can have a three-dimensional porous structure with high connectivity, which is conducive to the entry of nutrients, the growth of cells and tissues, and can promote cell adhesion and proliferation, etc., and can also promote bone growth.

[0062] In some embodiments, the bracket body 110 is a cubic structure with a hollow structure. A first hole 1111 is provided in the middle of a side surface of the cubic structure. An angular wall 112 is provided around the first hole 1111 . A plurality of second holes 1112 are distributed on the angular wall 112 .

[0063] Optionally, the length of the prism 112 is 100 μm to 500 μm, and the width of the prism 112 is 10 μm to 50 μm. Further, the length of the prism 112 is 150 μm to 300 μm, and the width of the prism 112 is 20 μm to 40 μm. Further, the length of the prism 112 is 180 μm to 220 μm, and the width of the prism 112 is 25 μm to 35 μm. As an example, the length of the prism 112 may be 100 μm, 120 μm, 150 μm, 180 μm, 200 μm, 220 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, 500 μm, or a range consisting of any two values; the width of the prism 112 may be 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, 50 μm, or a range consisting of any two values;

[0064] In the present application, the bracket body 110 may be a cubic structure as a whole, such as a rectangular parallelepiped structure or a cube structure, and the cubic structure has a hollow structure. The side of the cubic structure with a hollow structure, such as the middle of each side, is provided with a first hole 1111, and the periphery of the first hole 1111 is an edge wall 112, and a plurality of second holes 1112 are distributed on the edge wall 112, wherein the size of the first hole 1111 is larger than the size of the second hole 1112.

[0065] Thus, compared to conventional millimeter-level cartilage repair scaffolds, the size of the cartilage scaffold of the present application can be micrometer-level, reducing the size of the scaffold, and achieving a smaller physical size of the scaffold body, which is conducive to the entry of nutrients and the growth of cells and tissues. By making the edge length, edge width, and porosity of the scaffold body with a hollow cubic structure within the above range, compared to the existing spherical porous scaffold, the scaffold body 110 of the present application can be reorganized into an interconnected pore structure 201 after secondary structural reorganization, which is more convenient for the growth of cartilage cells.

[0066] In addition, most of the existing spherical porous scaffolds are porous structures of about 50 μm formed by the oil-in-water (WOW) emulsification method. Whether the pores are connected is random, so it cannot be confirmed that they are completely interconnected. However, the cubic structure of the present application can be assembled to form a completely horizontal and vertical connection, that is, to form the pore structure 201 described in the cartilage repair scaffold combination 20.

[0067] Optionally, the pore size of the porous structure 111 is 5 μm to 25 μm. As an example, the pore size of the porous structure 111 may be 5 μm, 6 μm, 8 μm, 10 μm, 12 μm, 15 μm, 18 μm, 20 μm, 25 μm, or a range of any two values.

[0068] It should be noted that the pore size of the porous structure 111 refers to the pore size of the second pore 1112, and the pore size of the first pore 1111 is not limited. In addition, the pore size of the porous structure 111 can be adaptively adjusted according to the size of the prism 112, and the specific value of the pore size of the second pore 1112 is not limited.

[0069] It should also be pointed out that the shapes of the first hole 1111 and the second hole 1112 shown in the accompanying drawings are only schematic. The first hole 1111 and the second hole 1112 can be conventional circular, square or other structures, or can also be other regular or irregular structures such as elliptical, triangular, hexagonal, etc., and the present application does not limit this.

[0070] In some embodiments, the scaffold body 110 is loaded with cartilage-derived stem cells 120 .

[0071] In the present application, the manufacturing material of the scaffold body 110 includes a photoresist such as IP-Visio photoresist, and the cartilage-derived stem cells 120 are loaded through the cell adhesion ability of the IP-Visio photoresist. The cartilage-derived stem cells 120 are inoculated on the scaffold body 110 and cultured in DMEM / F12 culture medium. After a 3-day culture period, cytoskeleton staining is used to observe the adhesion status of the stem cells on the scaffold body 110.

[0072] The above-mentioned DMEM / F12 culture medium includes DMEM culture medium, F12 culture medium or a mixed culture medium consisting of DMEM culture medium and F12 culture medium.

[0073] Therefore, the present invention can implant a cartilage repair scaffold 10 for repairing defective cartilage through fine needle puncture, and then achieve precise displacement of the cartilage repair scaffold 10 to the cartilage defect area under the control of an external magnetic field, and then achieve secondary cross-linking and solidification of the cartilage repair scaffold by ultrasonic heating to about 40°C. Subsequently, the cartilage-derived stem cells 120 carried by the cartilage repair scaffold obtain nutrition and proliferate through the pores in the scaffold body 110 to complete the in situ regeneration of cartilage.

[0074] In some embodiments, a method for preparing the cartilage repair scaffold as described above is provided, the method comprising the following steps:

[0075] Mixing the photoresist, the magnetic material and the photocurable biocompatible material in a certain ratio to obtain a mixed material;

[0076] The mixed material is printed by 3D printing to obtain the bracket body 110 .

[0077] It should be understood that all the features and advantages described above for the "cartilage repair scaffold" are also applicable to the "method for preparing the cartilage repair scaffold", and will not be described in detail here.

[0078] In the present application, the stent body 110 can be prepared by photopolymerization micro-nano 3D printing technology. The photoresist, magnetic material and photocurable biocompatible material are mixed in a certain proportion, such as the mass ratio of magnetic material, photoresist and photocurable biocompatible material is 1:5~15:20~40. The mixture is directly added to a photopolymerization micro-nano 3D printer for printing to obtain the stent body 110.

[0079] It should be noted that there is no special restriction on the establishment of the 3D printing model, and any existing 3D printing software can be used. The specific operating conditions of 3D printing can be selected and adjusted by those skilled in the art, and no specific limitation is made thereto.

[0080] In some embodiments, the cartilage-derived stem cells 120 are seeded in the scaffold body 110 and cultured in a culture medium; the culture medium includes DMEM culture medium, F12 culture medium, or a mixed culture medium consisting of DMEM culture medium and F12 culture medium.

[0081] In the present application, the stent body 110 is loaded with cartilage-derived stem cells 120 through the cell adhesion ability of IP-Visio photoresist, the cartilage-derived stem cells 120 are inoculated on the stent body 110, and cultured in DMEM / F12 culture medium, and after a 3-day culture period, cytoskeleton staining is used to observe the adhesion of stem cells on the stent body 110. The above-mentioned DMEM / F12 culture medium includes DMEM culture medium, F12 culture medium or a mixed culture medium consisting of DMEM culture medium and F12 culture medium.

[0082] It should be understood that DMEM medium and F12 medium are culture media known in the prior art, and this application does not limit them.

[0083] like Figure 2 As shown, in some embodiments, a cartilage repair scaffold assembly 20 includes a plurality of cartilage repair scaffolds as described above or prepared by the described method; wherein the plurality of scaffold bodies 110 interact with each other to generate cross-links to form a cartilage scaffold assembly.

[0084] In some embodiments, in the cartilage repair scaffold assembly 20, the porous structures 111 in the plurality of scaffold bodies 110 form an interconnected pore structure 201.

[0085] In some embodiments, multiple stents are subjected to secondary curing under the action of ultrasound to generate crosslinks, and the curing temperature is 38°C to 42°C. As an example, the curing temperature can be 38°C, 39°C, 40°C, 41°C, 42°C, or a range of any two values. The curing temperature is preferably around 40°C.

[0086] Thus, through the mechanical effect of ultrasound and the temperature effect of about 40° C., the scaffold body can be secondary cured to produce cross-linking, forming a cartilage repair scaffold assembly 20 .

[0087] In this application, the cartilage repair scaffold 10 can be injected into the joint, and then the group can be controlled and moved to the cartilage defect area under the control of the external magnetic field. The magnetic field can be an EMA magnetic control system, which can be composed of 6 electromagnetic coils. By adjusting the coil current, a maximum field strength of 100mT and 1.5Tm can be generated in the working space. -1The gradient magnetic field can directionally control the motion trajectory of the cartilage repair scaffold 10 through the change of the field strength. In addition, the present application also provides a cartilage repair scaffold assembly 20, that is, a cartilage injury repair scaffold with secondary cross-linking and curing. The cartilage repair scaffold assembly 20 includes the scaffold body of the aforementioned cartilage repair scaffold and the stem cells loaded thereon. In practical applications, the cartilage repair scaffold can be secondary cured by ultrasonic heating to about 40°C; the principle of the secondary curing is that the hydrogen bonds and hydrophobic interactions between the methacrylylated polycaprolactone (PCLMA) molecules are cross-linked due to the increase in temperature, forming a cross-linked network structure to achieve cross-linking and conformational changes of the micro-nano robot scaffold and curing to reside in the cartilage defect area.

[0088] The present application is further described below in conjunction with specific embodiments.

[0089] Example 1

[0090] like Figure 1 As shown, a cartilage repair stent 10 includes a stent body 110 , and the material of the stent body 110 includes photoresist, magnetic material and photocurable biocompatible material; the stent body 110 is a hollow structure with a porous structure 111 .

[0091] In the bracket body 110 of this embodiment, IP-Visio photoresist, ferroferric oxide (Fe3O4) and methacryloyl polycaprolactone (PCLMA) are mixed in a mass ratio of 1:10:30, and prepared by photopolymerization micro-nano 3D printing technology. The above materials are directly mixed and added to the photopolymerization micro-nano 3D printer for printing to obtain the bracket body 110. The bracket body 110 is a hollow cubic structure, the porosity of the bracket body 110 is 75%, the length of the prism 112 is 200μm, and the width of the prism 112 is 30μm.

[0092] The scaffold body 110 is loaded with cartilage-derived stem cells 120 through the cell adhesion ability of IP-Visio photoresist, and the cartilage-derived stem cells 120 are inoculated on the scaffold body 110 and cultured in DMEM / F12 culture medium. After a 3-day culture period, cytoskeleton staining is used to observe the adhesion of stem cells on the scaffold body 110.

[0093] like Figure 2 As shown, a cartilage repair scaffold assembly 20 is a cartilage damage repair scaffold after secondary cross-linking and curing. The cartilage repair scaffold assembly 20 is the scaffold body 110 of the aforementioned cartilage repair scaffold and the stem cells loaded therein. The cartilage repair scaffold is ultrasonically heated to about 40°C to achieve conformational change and curing of the cartilage repair scaffold to reside in the cartilage defect area.

[0094] Figure 3Confocal images of cartilage-derived stem cells on a cartilage repair scaffold are shown. Figure 3 As shown, Figure 3 Cytoskeleton staining was used to evaluate the morphology and attachment status of cartilage-derived stem cells after culture on the micro-nano scaffold. The F-actin staining of the cytoskeleton morphology was green and dispersed throughout the scaffold, showing a spindle-shaped morphology and a better cell diffusion area, which confirmed the better adhesion and proliferation of stem cells on the micro-nano scaffold itself.

[0095] Figure 4 The Micro-CT (micro-CT) and pathological results of in situ cartilage regeneration of the cartilage repair scaffold (cartilage defect repair micro-nano scaffold) are shown, Figure 4 As shown, Figure 4 Micro-CT, H&E and Safranin-O / Fast Green staining were used to evaluate the cartilage defect area. The Micro-CT three-dimensional reconstruction image showed that the area of ​​the cartilage defect was significantly reduced, and the results showed that there were newly grown chondrocytes in the defect area.

[0096] Parts not described in detail in the specification of the present invention are well known to those skilled in the art.

[0097] In the present invention, the terms "one embodiment", "some embodiments", "examples", "specific examples" or "some examples" etc. mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, unless they are contradictory.

[0098] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A cartilage repair scaffold, characterized in that: The cartilage repair scaffold comprises a scaffold body, and the material of the scaffold body comprises photoresist, magnetic material and photocurable biocompatible material; The support body is a hollow structure with a porous structure.

2. The cartilage repair scaffold according to claim 1, characterized in that: The porosity of the stent body is 60% to 80%; And / or, the pore size of the porous structure is 5 μm to 25 μm.

3. The cartilage repair scaffold according to claim 1, characterized in that: The support body is a cubic structure with a hollow structure, a first hole is provided in the middle of a side surface of the cubic structure, a prism wall is provided around the first hole, and a plurality of second holes are distributed on the prism wall; The length of the ridge wall is 100 μm to 500 μm, and the width of the ridge wall is 10 μm to 50 μm.

4. The cartilage repair scaffold according to claim 1, characterized in that: The mass ratio of the magnetic material, the photoresist and the photocurable biocompatible material is 1:5-15:20-40.

5. The cartilage repair scaffold according to claim 1, characterized in that: The photoresist comprises IP-photoresist; And / or, the magnetic material includes ferrosoferric oxide; And / or, the photocurable biocompatible material comprises methacrylated polycaprolactone.

6. The cartilage repair scaffold according to any one of claims 1 to 5, characterized in that: The scaffold body is loaded with cartilage-derived stem cells.

7. The method for preparing a cartilage repair scaffold according to any one of claims 1 to 6, characterized in that: The following steps are involved: mixing a photoresist, a magnetic material and a photocurable biocompatible material to obtain a mixed material; The mixed material is printed by 3D printing to obtain a stent body.

8. The method for preparing the cartilage repair scaffold according to claim 7, characterized in that: The method further comprises: The cartilage-derived stem cells are inoculated into the scaffold body and cultured in a culture medium; the culture medium includes DMEM culture medium, F12 culture medium or a mixed culture medium consisting of DMEM culture medium and F12 culture medium.

9. A cartilage repair scaffold assembly, characterized in that: The cartilage repair scaffold combination comprises a plurality of cartilage repair scaffolds according to any one of claims 1 to 6 or cartilage repair scaffolds prepared by the method according to any one of claims 7 to 8; Wherein, a plurality of the scaffold bodies interact with each other to generate cross-links to form the cartilage scaffold combination.

10. The cartilage repair scaffold assembly according to claim 9, characterized in that: In the cartilage repair stent assembly, the porous structures in the plurality of stent bodies form interconnected pore structures; And / or, the plurality of stents are subjected to secondary curing under the action of ultrasound to generate cross-linking, and the curing temperature is 38° C. to 42° C.

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