Demineralized cartilage matrix scaffolds and apoptotic body compositions for repairing cartilage and methods of making the same

Abstract

The application discloses a kind of for repairing cartilage decellularized cartilage matrix support and apoptotic corpuscle composition and its preparation method, composition includes: microporous support, support includes decellularized cartilage outer matrix and crosslinked organic polymer;Apoptotic corpuscle, apoptotic corpuscle exists in microporous support;Wherein, based on the volume 3.14mm 3 Microporous support, 0.01-0.02ug of apoptotic corpuscle is included.The combined support of the application can improve the activity of apoptotic corpuscle, prolong the action time of apoptotic corpuscle, achieve the effect of slow release, also can regulate joint cavity microenvironment, effectively promote joint cartilage repair, improve the repair effect of loss cartilage, avoid the security risks brought by traditional exogenous cell transplantation.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical materials, and particularly relates to a decellularized cartilage matrix scaffold and apoptotic corpuscle composition for repairing cartilage and a preparation method thereof. BACKGROUND

[0002] Articular cartilage, lacking blood vessels, nerves and lymphatic vessels, is difficult to repair itself once damaged, and severe damage can lead to osteoarthritis. With the popularization of social fitness exercises, the number of patients with articular cartilage damage is increasing, and the age tends to be younger.

[0003] In related art, articular cartilage damage is mainly treated by surgery, including joint debridement, microfracture, autologous periosteal transplantation, autologous osteochondral transplantation and autologous chondrocyte transplantation. Surgical treatment brings many inconveniences to patients, and a new means or product is urgently needed to repair the damaged cartilage. SUMMARY

[0004] In view of this, the present application provides a decellularized cartilage matrix scaffold and apoptotic corpuscle composition for repairing cartilage and a preparation method thereof, aiming to provide a composition that can effectively regulate the microenvironment of the joint cavity and promote the repair of articular cartilage.

[0005] In a first aspect, the embodiments of the present application provide a decellularized cartilage matrix scaffold and apoptotic corpuscle composition for repairing cartilage, comprising:

[0006] The microporous scaffold comprises a decellularized cartilage extracellular matrix and a cross-linked organic polymer;

[0007] The apoptotic corpuscle exists in the microporous scaffold.

[0008] The microporous scaffold has a volume of 3.14mm 3 The microporous scaffold contains 0.01-0.02ug of apoptotic corpuscles.

[0009] According to an embodiment of the present application, based on the total weight of the microporous scaffold, 95-99% of the decellularized cartilage extracellular matrix and 1-5% of the cross-linked organic polymer are contained.

[0010] According to an embodiment of the present application, the raw material of the cross-linked organic polymer comprises carbodiimide and N-hydroxysulfonimide.

[0011] According to an embodiment of the present application, the decellularized cartilage extracellular matrix constitutes a porous support, and the cross-linked organic polymer is distributed on the surface and at least part of the pores of the support.

[0012] The microporous scaffold has a volume of 3.14mm 3the microporous scaffold of the first aspect, comprising 10 4 -10 7 apoptotic bodies.

[0013] According to an embodiment of the aspect of the application, the composition satisfies at least one of the following conditions:

[0014] The apoptotic bodies are derived from human umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, or a combination thereof.

[0015] The particle size of the apoptotic bodies is 200-4800 nm.

[0016] The decellularized cartilage extracellular matrix is derived from pigs, cattle, horses, or a combination thereof.

[0017] In a second aspect, the application provides a preparation method of a decellularized cartilage matrix scaffold and apoptotic body composition for repairing cartilage, comprising:

[0018] respectively providing a decellularized cartilage extracellular matrix solution and an apoptotic body solution;

[0019] freeze-drying the decellularized cartilage extracellular matrix solution to obtain a microporous solid-phase matrix;

[0020] mixing the microporous solid-phase matrix with an organic polymer solution, and cross-linking under heating conditions to obtain a microporous scaffold containing cross-linked organic polymers;

[0021] dispersing the apoptotic body solution in at least part of the micropores of the microporous scaffold to obtain the composition of the first aspect.

[0022] According to an embodiment of the aspect of the application,

[0023] The concentration of the apoptotic body solution is 0.8-1.2 μg / ml, and optionally 1 μg / ml.

[0024] According to an embodiment of the aspect of the application,

[0025] After obtaining the microporous scaffold containing cross-linked organic polymers, further comprising: rinsing the cross-linked microporous scaffold with a buffer and sterilizing.

[0026] According to an embodiment of the aspect of the application,

[0027] The apoptotic body solution comprises a buffer selected from a second solute selected from a phosphate, sodium chloride, or a combination thereof.

[0028] Compared with the prior art, the application has at least the following beneficial effects:

[0029] The composition for repairing cartilage injury provided in the application utilizes the decellularized cartilage extracellular matrix and a buffer to prepare a scaffold structure with micropores, and the microporous scaffold after crosslinking has a more suitable strength for use, and the apoptotic bodies cooperate with the microporous scaffold, which can improve the activity of the apoptotic bodies, prolong the action time of the apoptotic bodies, achieve a slow-release effect, and on the other hand, the cooperation of the two can regulate the joint cavity microenvironment, effectively promote the repair of articular cartilage, improve the repair effect of lost cartilage, and avoid the safety hazards brought by traditional exogenous cell transplantation. The preparation method of the application has a simple process and strong operability, and is suitable for batch production. BRIEF DESCRIPTION OF DRAWINGS

[0030] In order to more clearly illustrate the technical solutions of the embodiments of the application, the drawings needed to be used in the embodiments of the application will be briefly introduced as follows. Obviously, the drawings described below are only some embodiments of the application, and other drawings can be obtained by the drawings without creative labor for those skilled in the art.

[0031] Figure 1 A transmission electron microscope image of the apoptotic bodies prepared in Example 1 of the application is shown;

[0032] Figure 2 A protein electrophoresis image expressed by the apoptotic bodies prepared in Example 1 of the application is shown;

[0033] Figure 3 A particle size distribution graph of the apoptotic bodies prepared in Example 1 of the application is shown;

[0034] Figure 4 A specific protein staining image of the apoptotic bodies in Example 1 of the application is shown;

[0035] Figure 5 A comparison graph of the repair effect of rat bone cartilage in the embodiment of the application is shown;

[0036] Figure 6 A repair score graph of rat bone cartilage in the embodiment of the application is shown;

[0037] Figure 7 A staining image of a repair section of rat bone cartilage at 6 weeks in the embodiment of the application is shown;

[0038] Figure 8 A staining image of a repair section of rat bone cartilage at 12 weeks in the embodiment of the application is shown;

[0039] Figure 9 A cartilage repair score graph in the embodiment of the application is shown. DETAILED DESCRIPTION

[0040] In order to make the application purposes, technical solutions and beneficial technical effects of the present application clearer, the present application will be further described in detail below in combination with embodiments. It should be understood that the embodiments described in the specification are only for the purpose of explaining the present application and are not intended to limit the present application.

[0041] For the sake of simplicity, only some numerical ranges are explicitly recited herein. However, any lower limit can be combined with any upper limit to form a range not explicitly recited; and any lower limit can be combined with any other lower limit to form a range not explicitly recited, and likewise any upper limit can be combined with any other upper limit to form a range not explicitly recited. Furthermore, although a range of endpoints is recited, each point or individual number within the range is also included in the range. Thus, each point or individual number can be combined as its own lower or upper limit with any other point or individual number or with other lower or upper limits to form a range not explicitly recited.

[0042] In the description of the present application, it should be noted that, unless otherwise specified, "above", "below" are inclusive of the number, and the meaning of "multiple" in "one or more" is two and more than two.

[0043] The above application content of the present application is not intended to describe each disclosed embodiment or each implementation in the present application. The exemplary embodiments are illustrated more specifically in the following description. In many places throughout the application, guidance is provided by a series of embodiments, which can be used in various combinations. In each instance, the enumeration is only representative of a group, and should not be interpreted as exhaustive.

[0044] Articular cartilage, lacking blood vessels, nerves and lymphatic vessels, is difficult to repair itself once damaged, eventually leading to the occurrence of osteoarthritis. With the popularity of social fitness exercise, the number of patients with articular cartilage injury is increasing, and the age tends to be younger.

[0045] The surgical treatment of articular cartilage injury mainly includes joint debridement, microfracture, autologous periosteal transplantation, autologous osteochondral transplantation and autologous chondrocyte transplantation. The long-term treatment effect of joint debridement is not ideal and the recurrence rate is high. The new tissue after microfracture is not hyaline cartilage, but fibrocartilage-like repair, which is poor in structure and function. Autologous free periosteal transplantation often uses the periosteum in front of the tibia, but the ability of the periosteum to form cartilage surface is affected by many factors, such as age, donor location, direction of transplantation, etc., and the expected treatment effect is difficult to determine. Autologous cartilage transplantation has good repair effect for small area of cartilage injury, but the supply area is limited, and allogeneic cartilage transplantation has a wide source, but due to the risk of rejection and disease transmission, it is difficult to achieve large-scale clinical application.

[0046] Based on this, the inventors have conducted a large amount of research aimed at providing a composition for repairing cartilage damage, which can efficiently repair cartilage damage while solving the above problems.

[0047] The application provides a decellularized cartilage matrix scaffold and apoptotic body composition for repairing cartilage, comprising:

[0048] The microporous scaffold comprises a decellularized cartilage extracellular matrix and a crosslinked organic polymer;

[0049] The apoptotic bodies are present in the microporous scaffold.

[0050] The microporous scaffold has a volume of 3.14mm 3 The microporous scaffold contains 0.01-0.02ug of apoptotic bodies.

[0051] The vesicles include exosomes, apoptotic bodies, and apoptotic vesicles. Studies have found that compared with traditional repair techniques such as microfracture, stem cells have the potential to form more typical hyaline cartilage and can better control the symptoms of cartilage loss. Compared with autologous chondrocytes, stem cells have a wider source and stronger in vitro expansion capacity, but the use of stem cells may bring problems such as loss of stemness during in vitro transportation and storage, tumorigenicity of stem cells, immunogenicity of stem cells, difficulty in standardizing stem cell therapy, etc. Studies have found that living cells cannot be considered as off-the-shelf products for clinical applications. Instead, stem cell paracrine factors replace stem cell therapy, which can overcome the shortcomings of living cell therapy and provide a cell-free clinically feasible therapy. Compared with traditional stem cell therapy, stem cell paracrine factors have the following characteristics. The currently studied stem cell exosomes have a similar cartilage repair effect as stem cells.

[0052] Further studies have found that apoptotic bodies have the characteristics of easy penetration into tissues, low immunogenicity, and easy storage during tissue regeneration and embryogenesis. Apoptotic bodies produced after cell apoptosis contain a variety of active small molecule substances that promote the repair and regeneration of adjacent cells. Studies have found that most transplanted cells undergo apoptosis in a short period of time after exogenous stem cell transplantation, indicating that stem cell transplantation still plays a certain effect.

[0053] The technical solution of the application uses a decellularized cartilage extracellular matrix scaffold (DCM) to interact with apoptotic bodies, which has a good effect of promoting cartilage regeneration and repair. In addition, in clinical use, the patient's own chondrocytes can be used for preparation.

[0054] In some embodiments, the micro-porous scaffold comprises 95%-99% of the decellularized cartilage extracellular matrix based on the total weight of the micro-porous scaffold. The decellularized cartilage extracellular matrix in the above mass fraction exists in the cartilage matrix, which can realize the supporting effect of the scaffold on one hand, and the decellularized cartilage extracellular matrix in a suitable mass fraction can promote cell adhesion, proliferation and chondrogenic differentiation on the other hand.

[0055] In some embodiments, the raw material of the cross-linked organic polymer comprises carbodiimide and N-hydroxyl sulfone imide.

[0056] In some embodiments, the decellularized cartilage extracellular matrix constitutes a porous support, and the cross-linked organic polymer is distributed on the surface and at least part of the pores of the support. The decellularized cartilage extracellular matrix of the present application can constitute a solid scaffold structure on one hand, and has micro-pores; on the other hand, the distribution of the cross-linked organic polymer on the surface and at least part of the pores of the support can effectively improve the mechanical strength of the support, which is beneficial to subsequent use.

[0057] In some embodiments, the micro-porous scaffold with a volume of 3.14 mm 3 contains 10 4 -10 7 apoptotic bodies. The loading of the appropriate concentration of apoptotic bodies in the appropriate volume of the micro-porous scaffold can improve the combined effect of the apoptotic bodies and the micro-porous scaffold on one hand, and can maintain the vitality of the apoptotic bodies, which can achieve long-term and sustained repair and regulation of the microenvironment.

[0058] In some embodiments, the method for preparing the apoptotic bodies comprises: inducing cell apoptosis of human umbilical cord mesenchymal stem cells, and continuing to culture in complete medium;

[0059] Taking the supernatant in the complete medium, the apoptotic bodies are obtained from the supernatant.

[0060] In some embodiments, the timing of inducing cell apoptosis of human umbilical cord mesenchymal stem cells is after proliferation, and the density of human umbilical cord mesenchymal stem cells in adherent culture is 80-90%. Generally, the density of 50% is used for culture at the initial stage of culture.

[0061] In some embodiments, the human umbilical cord mesenchymal stem cells can be induced to undergo cell apoptosis by using staurosporine (STS), ultraviolet irradiation or a combination thereof.

[0062] In some embodiments, the apoptotic bodies express proteins Histone H3.3, protein Histone H2B, protein C3b and protein C1QC. The above proteins are unique proteins for identifying apoptotic bodies, and these proteins can be used to determine that these vesicles are apoptotic bodies.

[0063] In some embodiments, the apoptotic bodies have a spherical morphology.

[0064] In some embodiments, the apoptotic bodies are derived from stem cells.

[0065] According to the embodiments of the present application, the apoptotic bodies can promote cell proliferation, migration, and phenotype change of macrophages by activating energy metabolism of cells; the apoptotic bodies and the microporous scaffold in the composition do not contain living cells, thus avoiding the safety hazards caused by the use of exogenous cell transplantation and having high biological safety; the combination of the apoptotic bodies and the decellularized cartilage extracellular matrix effectively regulates the cartilage regeneration microenvironment and promotes repair of damaged cartilage.

[0066] In some embodiments, the composition satisfies at least one of the following conditions:

[0067] The apoptotic bodies are derived from human umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, adipose tissue mesenchymal stem cells, or a combination thereof; the apoptotic bodies derived from the above sources have better cartilage repair ability and stronger activity.

[0068] The particle size of the apoptotic bodies is 200-4800 nm; the apoptotic bodies with the above particle size are more easily attached to the microporous scaffold and are more easily phagocytosed by endogenous stem cells and macrophages, thereby playing a role in promoting cartilage regeneration and repair.

[0069] The decellularized cartilage extracellular matrix is derived from pigs, cattle, horses, or a combination thereof.

[0070] In some embodiments, the cross-linked polymer can be prepared by carbodiimide and N-hydroxysulfonimide cross-linking, and the cross-linking method can be vacuum dry physical method cross-linking, ultraviolet cross-linking. The cross-linking conditions can be cross-linking of aldehyde compounds for 1h-48h, or cross-linking of carbodiimide compounds for 1h-48h.

[0071] In a second aspect, the present application provides a preparation method of a decellularized cartilage matrix scaffold and apoptotic body composition for repairing cartilage, comprising:

[0072] A decellularized cartilage extracellular matrix solution and an apoptotic body solution are respectively provided;

[0073] The decellularized cartilage extracellular matrix solution is freeze-dried to obtain a microporous solid phase matrix;

[0074] The microporous solid phase matrix is mixed with an organic polymer solution, and cross-linking is performed under heating conditions to obtain a microporous scaffold containing cross-linked organic polymers;

[0075] The apoptotic body solution is dispersed in at least part of the micropores of the microporous scaffold to obtain the composition.

[0076] In some embodiments, the suspension includes a first solute selected from the group consisting of a phosphate, sodium chloride, or a combination thereof.

[0077] In some embodiments, the concentration of the suspension is 0.5%-2%. The solid-phase suspension in the present application can make the structure of the decellularized cartilage extracellular matrix have micropores after freeze-drying, which can improve its repair and regulation ability in the later use process, and also can improve the activity of the apoptotic bodies.

[0078] According to the embodiments of the present application, by freeze-drying the decellularized cartilage extracellular matrix solution, on the one hand, the activity of the decellularized cartilage extracellular matrix can be effectively preserved, which is convenient for its later effect on the damaged cartilage, and on the other hand, part of the solvent in the decellularized cartilage extracellular matrix solution can be removed, and the obtained solid material has many micropores, which is convenient for the subsequent slow release and effect of the apoptotic bodies.

[0079] In some embodiments, the concentration of the apoptotic body solution is 0.8-1.2 μg / ml, which can be 1 μg / ml. By selecting the apoptotic bodies with a concentration of 0.8-1.2 μg / ml, the activity of the apoptotic bodies can be maintained, and the effect of repairing the cartilage and regulating the cartilage microenvironment can be improved.

[0080] In some embodiments, after obtaining the microporous scaffold containing the crosslinked organic polymer, the crosslinked microporous scaffold is further rinsed with a buffer and sterilized.

[0081] Examples

[0082] The following examples more specifically describe the present disclosure, which are only used for illustrative purposes, because various modifications and changes within the scope of the present disclosure are obvious to those skilled in the art. Unless otherwise stated, all parts, percentages, and ratios reported in the following examples are by weight, and all reagents used in the examples are commercially available or synthesized according to conventional methods and used directly without further purification, and the instruments used in the examples are commercially available.

[0083] Example 1

[0084] Preparation of apoptotic bodies: human umbilical cord mesenchymal stem cells in good growth state extracted from neonatal umbilical cord were approved by the ethics committee of the People's Liberation Army General Hospital, and when the human umbilical cord mesenchymal stem cells reached 80-90% of the confluence, staurosporine (STS) was used to induce cell apoptosis, and the cells were further cultured in complete medium for 24 hours. The cell culture supernatant was centrifuged at 300g for 10 minutes, and the supernatant was further centrifuged at 12000g at 4°C for 30 minutes. The obtained precipitate was the apoptotic bodies of stem cells.

[0085] The precipitate was detected by a JEM-1200EX transmission electron microscope, and the apoptotic bodies were observed. The transmission electron microscope image is shown in FIG. 1, and the morphology is spherical. Figure 1 The prepared apoptotic bodies were verified by WB (immunoblotting), and the apoptotic body protein electrophoresis image is shown in FIG. 2. In the figure, the first column represents human umbilical cord mesenchymal stem cells, and the second column represents apoptotic bodies. It was found that Histone H3.3, Histone H2B, C3b, and C1QC proteins were expressed. Figure 2 The apoptotic body solution was detected by dynamic light scattering, and the apoptotic body particle size distribution is shown in FIG. 3. The particle size is 200-4800 nm. Figure 3

[0086] Example 2

[0087] Preparation of porcine-derived decellularized cartilage extracellular matrix: Fresh porcine femur was obtained from the market, and the articular cartilage of the femoral condyle and femoral head was cut off with a scalpel. After washing with sterile distilled water for 3 times, the cartilage fragments were soaked in 1% acetic acid for 3 times / 30 minutes, washed with sterile distilled water for 3 times, 30 minutes each time, and stored at -80°C. Then, 500 ml of hydrogen peroxide was used to soak twice, 1 hour each time, and distilled water was used to soak 5 times, 20 minutes each time, and stored at -80°C. After thawing, the cartilage pieces were washed with deionized water for 2 times, 10 minutes each time, then pre-cooled deionized water was added to the pulverizing cup for complete pulverization. After sufficient pulverization, the supernatant was taken after centrifugation at 1000 rpm for 10 minutes. The precipitate was mixed with water and centrifuged repeatedly to take the supernatant. The collected supernatant was centrifuged at 6000 rpm for 30 minutes, and the upper cell-free layer was collected. The precipitate was obtained by centrifugation at 10000 rpm for 40 minutes, which was the cell cartilage extracellular matrix.

[0088] The collected precipitate was mixed with 50 u / ml DNAase + 1 U / ml RNAase solution and placed at 4°C for 4 hours. Then, it was centrifuged at 10000 rpm for 40 minutes to obtain 4% decellularized cartilage matrix (DCM).

[0089] Example 3

[0090] Preparation method of microporous scaffold: The DCM prepared in Example 2 was washed with sterile distilled water, and then distilled water was added to prepare a suspension of 0.5%-2% w / v.

[0091] The above suspension was placed in a cylindrical mold and frozen at -20°C for 12 hours, then frozen at -80°C for 1 hour, and then freeze-dried in a freeze-drying machine for 48 hours.

[0092] ​The freeze-dried scaffolds were immersed in a mixed aqueous solution of carbodiimide compound and N-hydroxysuccinimide for 1 h to 48 h, and the excess cross-linking solution was washed off the scaffolds by soaking in distilled water. The microporous scaffolds with a diameter of 2 mm and a thickness of about 1 mm were produced by drying and cutting, and finally sterilized by gamma irradiation at 5 mRad. 60 Coγ-ray irradiation for sterilization.

[0093] Example 4

[0094] Preparation of the decellularized cartilage matrix scaffold and apoptotic body composition for repairing cartilage: After the apoptotic bodies of Example 1 dissolved in phosphate buffer were quantified by protein (BCA method), 20 μl (1 μg / ml) of the apoptotic body suspension was injected into each scaffold (2 mm in diameter and about 1 mm in thickness) using a microsyringe, and then implanted into the cartilage defect of the knee joint cavity of rats, and 20 μl of the apoptotic bodies (1 μg / ml) was injected into the surgical joint cavity of rats at 3, 7, and 14 days, respectively.

[0095] Test section

[0096] 1) Annexin V fluorescent staining specific to apoptotic bodies: Annexin V-FITC dye with a concentration of 1 μg / ml was used to stain the apoptotic bodies prepared in Example 1, and the pictures as shown in FIG. 1 show that the apoptotic bodies can be stained with Annexin V, and also show that the apoptotic bodies are spherical vesicles. Figure 4

[0097] 2) Rat osteochondral repair experiment: Using a random control grouping method, male SD rats from the Holy Water Toad Co., Ltd. were used, with the body weight and number of rats in each group being 250 g ± 50 g (n = 5), respectively. A corneal trephine with a diameter of 2 mm was used to drill a hole in the trochlear groove to form a full-thickness cylindrical osteochondral defect with a depth of 1.5 mm. Different groups of rats were treated, including a control group (control) without treatment, an Abs group treated with the apoptotic bodies of Example 1, a DCM group treated with the decellularized soft outer matrix of Example 2, and a DCM+Abs group treated with the composition of Example 4. In addition to the control group and the DCM group, 20 μl of 1 μg / ml ABs was injected into the joint cavity of the other two groups during the operation and at 3, 7, and 14 days after the operation, respectively. Six weeks and 12 weeks after the operation, the samples were taken and photographed, and the results are shown in FIG. 2. It can be seen from the figure that the DCM+Abs group treated with the decellularized cartilage matrix scaffold and apoptotic body composition for repairing cartilage of Example 4 has the best effect. Figure 5

[0098] ​​The effect of the bone cartilage repair experiment on rats was scored according to the scoring rules of the International Cartilage Repair Society (ICRS) to obtain the general cartilage repair score as shown in Figure 6 The higher the score, the better the effect. As can be seen from the effects after 6 weeks and 12 weeks of treatment, the composition of the example has the best effect on cartilage repair.

[0099] 4) Staining section experiment: The knee joint trochlea paraffin sections of rats were stained with staining agents HE, Safranin O fast green and type II collagen respectively to obtain the effects as shown in Figure 7 and Figure 8 As can be seen from the figure, the composition of Example 4 has the best effect on DCM+Abs.

[0100] The cartilage repair histology of the section was scored using the modified O'Driscoll histology score to obtain the results as shown in Figure 9 The higher the score, the better the effect. As can be seen from the effects after 6 weeks and 12 weeks of treatment, the decellularized cartilage matrix scaffold and apoptotic corpuscle composition for repairing cartilage of the example has the best effect on cartilage repair.

[0101] The above is only a specific embodiment of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art can easily think of various equivalent modifications or replacements within the technical scope disclosed in the present application, and these modifications or replacements should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A composition of a decellularized cartilage matrix scaffold and apoptotic bodies for repairing cartilage, comprising: a microporous scaffold comprising 95-99% of a decellularized cartilage extracellular matrix and 1-5% of a cross-linked organic polymer based on the total weight of the microporous scaffold; the decellularized cartilage extracellular matrix forms a porous support, and the cross-linked organic polymer is distributed on the surface of the support and at least part of the pores, and the raw material of the cross-linked organic polymer comprises carbodiimide and N-hydroxysulfonimide; and apoptotic bodies, wherein the apoptotic bodies are present in the microporous scaffold. 2.The composition of claim 1, wherein: the composition satisfies at least one of the following conditions: the apoptotic bodies are derived from human umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells, adipose tissue mesenchymal stem cells, or a combination thereof; the particle size of the apoptotic bodies is 200-4800 nm; and the decellularized cartilage extracellular matrix is derived from pigs, cattle, horses, or a combination thereof. 4.A method for preparing a composition of a decellularized cartilage matrix scaffold and apoptotic bodies for repairing cartilage, comprising: providing a decellularized cartilage extracellular matrix solution and an apoptotic body solution, respectively; freeze-drying the decellularized cartilage extracellular matrix solution to obtain a microporous solid-phase matrix; mixing the microporous solid-phase matrix with an organic polymer solution, and cross-linking under heating to obtain a microporous scaffold comprising a cross-linked organic polymer; wherein the microporous scaffold comprises 95-99% of a decellularized cartilage extracellular matrix and 1-5% of a cross-linked organic polymer based on the total weight of the microporous scaffold; the decellularized cartilage extracellular matrix forms a porous support, and the cross-linked organic polymer is distributed on the surface of the support and at least part of the pores, and the raw material of the cross-linked organic polymer comprises carbodiimide and N-hydroxysulfonimide; and the concentration of the apoptotic body solution is 0.8-1.2 μg / ml. The concentration of the apoptotic body solution is 1 μg / ml. wherein the microwell scaffold based on a volume of 3.14 mm 3 contains 0.01-0.02 pg of apoptotic bodies. After obtaining the microporous scaffold comprising a cross-linked organic polymer, the method further comprises: rinsing the cross-linked microporous scaffold with a buffer and sterilizing. The composition based on volume 3.14 mm 3 comprises 10 4 -10 7 apoptotic bodies.

3. The composition of claim 1, wherein, The apoptotic body solution comprises a buffer selected from a second solute selected from a phosphate, sodium chloride, or a combination thereof. ​ ​ ​ ​ ​ ​ ​ ​ dispersing the apoptotic bodies solution into at least some of the microwells of the microwell scaffold, to obtain the composition, wherein 0.01-0.02 pg of apoptotic bodies are contained per 3.14 mm 3 of the microwell scaffold, based on volume.

5. The preparation method according to claim 4, characterized in that ​ 6. The production method according to claim 5, characterized by, ​ 7. The preparation method according to claim 4, characterized in that ​ 8. The preparation method according to claim 4, characterized in that ​

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