A wrinkled fruit-like bioceramic microparticle-based composite material and preparation and application thereof

Abstract

The application discloses a wrinkled fruit-like bioceramic microparticle-based composite material and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The preparation method comprises the following steps: 5-15% of bioceramic microparticles and 85-95% of microfiber gel are mixed according to the percentage by weight, and then a composite material is obtained through high-speed homogenization. The application provides a wrinkled fruit-like bioceramic microparticle-based composite material, which combines bioceramic microparticles and microfiber gel, has good biocompatibility, and can promote cell adhesion and tissue regeneration at a soft and hard tissue joint part. The composite material is particularly suitable for repairing tendon injury, and can effectively promote the regeneration of a tendon and a tendon-bone stop.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials, and particularly relates to a wrinkled fruit-shaped bioceramic microparticle-based composite material and a preparation method and application thereof. BACKGROUND

[0002] Tendons play a crucial role in movement by transmitting force from muscles to bones. However, due to the unique structure of tendons, their self-healing ability is poor, and the repair of large-area or severe injuries often requires surgical intervention. Tendon injury is a common type of tissue damage in clinical practice, which severely affects the patient's activity and quality of life. Traditional surgical repair methods are mainly based on suturing, but only partial mechanical properties of the tendon can be restored after suturing, and often the function is not fully recovered due to mechanical instability and insufficient biological healing. In tendon repair, the regeneration of the tendon-bone insertion is an important challenge. The tendon-bone insertion is a key area connecting the tendon and the bone, and its complex mechanical environment and structural characteristics make its healing more difficult. Traditional suturing techniques are difficult to effectively reconstruct the mechanical support and biological function of the tendon-bone insertion, so new repair materials and techniques need to be developed to promote the comprehensive repair of the tendon and the tendon-bone insertion.

[0003] In recent years, biological composites have attracted attention due to their extensive potential in soft and hard tissue repair. In particular, in the field of tendon repair, composite materials based on gel carriers and inorganic bioceramic microparticles have shown good application prospects. Gel carriers not only have excellent biocompatibility and biological activity, but also can promote the proliferation and differentiation of fibroblasts and osteoblasts by providing a suitable microenvironment for cells. At the same time, inorganic bioceramic microparticles in the composite material can provide a large surface for cell attachment, improve cell behavior, and further promote tissue regeneration and repair, providing new possibilities for the repair of the tendon-bone insertion.

[0004] Therefore, how to process inorganic ceramic materials into composite materials for treating tendon injuries is of great significance. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application provides a wrinkled fruit-shaped bioceramic microparticle-based composite material, which combines bioceramic microparticles and microfiber gel to have good biocompatibility and promote cell adhesion and tissue regeneration at soft and hard tissue junctions. The composite material is particularly suitable for the repair of tendon injuries and can effectively promote the regeneration of tendons and tendon-bone insertions, thereby solving the technical problems raised in the background art. Specifically, the technical scheme of the present application includes the following steps:

[0006] A wrinkled fruit-shaped bioceramic microparticle-based composite material, which is composed of 5% to 15% bioceramic microparticles and 85% to 95% microfiber gel by mass fraction.

[0007] Further, the preparation method of the bioceramic microparticles comprises the following steps:

[0008] The calcium phosphate, the silicate, water and the composite binder are mixed and ball milled, and then dried to obtain sub-micron ceramic powder;

[0009] The sub-micron ceramic powder and deionized water are mixed and stirred to form a spray slurry;

[0010] The spray slurry is subjected to high-temperature spray granulation at 220-240°C to obtain a bioceramic microparticle body;

[0011] The bioceramic microparticle body is sintered at a high temperature of 1250-1400°C for 1-2h, and then screened to obtain bioceramic microparticles with a particle size of 10-70μm.

[0012] Further, the calcium phosphate comprises hydroxyapatite and / or β-tricalcium phosphate.

[0013] Further, the silicate comprises xonotlite.

[0014] Further, the composite binder is composed of polyvinylpyrrolidone and dopamine hydrochloride at a weight ratio of 40:1-2, or composed of polyvinyl alcohol and dopamine hydrochloride at a weight ratio of 40:1-2.

[0015] Further, the weight ratio of the calcium phosphate: the silicate: water: the composite binder is 54-201:62-127:180-270:27-32.

[0016] Further, the ball milling conditions include a ball milling temperature of 25-30°C, a ball milling rotation speed of 500-600r / min, a ball milling time of 5-6h, and a ball milling pH of 8.5.

[0017] Further, the weight ratio of the sub-micron ceramic powder: deionized water is 179-184:358-394.

[0018] Further, the preparation method of the microfiber gel comprises the following steps:

[0019] The bovine dermal layer is subjected to a defatting and decellularization step to obtain a bovine decellularized dermal matrix collagen membrane material;

[0020] 2g of the bovine decellularized dermal matrix collagen membrane material is placed in 50mL of 0.1% acetic acid aqueous solution for 1h, and then taken out and drained to obtain a pretreated bovine decellularized dermal matrix collagen membrane material;

[0021] Pretreated bovine decellularized dermal matrix collagen membrane material was mixed with deionized water and then crushed through a 300-mesh sieve to obtain microfiber gel.

[0022] Furthermore, the weight ratio of the pretreated bovine decellularized dermal matrix collagen membrane material to deionized water is 30:110.

[0023] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material, the method comprising the following steps:

[0024] The composite material is obtained by mixing 5%–15% bioceramic microparticles and 85%–95% microfiber gel by weight percentage and then homogenizing at high speed.

[0025] Application of a wrinkled, fruit-like bioceramic microparticle-based composite material in the field of soft tissue repair.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0027] (1) The composite material prepared by the present invention has the characteristics of self-assembly and spontaneous gelation at body temperature. Compared with traditional patch or suture materials, it has more advantages in repairing tendon injuries in terms of biological healing, material compatibility and local microenvironment regulation.

[0028] (2) The bioceramic microparticles prepared by the present invention are wrinkled, with wrinkles and depressions on the surface, which increases the surface roughness of the microparticles, enhances cell adhesion, proliferation and differentiation, and helps to promote tissue regeneration.

[0029] (3) The bioceramic microparticles used in this invention are calcium phosphate or magnesium silicate, containing active elements of calcium, phosphorus, silicon and magnesium. They have good biocompatibility and bioactivity. After being injected into soft tissues, they have low immunogenicity and will hardly cause serious inflammatory reactions. On the other hand, their good bioactivity can promote the regeneration of soft tissues such as collagen and tendons. Attached Figure Description

[0030] Figure 1 SEM image of the bioceramic microparticles prepared in Example 1 of this invention, with a scale bar of 50 micrometers in the image;

[0031] Figure 2 SEM image of the bioceramic microparticles prepared in Example 2 of this invention, with a scale bar of 50 micrometers;

[0032] Figure 3 The graphs show the trend of viscosity change with temperature of the composite materials prepared in Examples 1-2 and Comparative Examples 1-6 of this invention.

[0033] Figure 4The results of inducing mesenchymal stem cell differentiation with the composite materials prepared in Examples 1-2 and Comparative Examples 1-4 of this invention;

[0034] Figure 5 This is a diagram illustrating the construction of the rotator cuff injury model of the present invention.

[0035] Figure 6 The results of H&E staining of the implantation site sample are obtained 2 months after the composite material prepared in Example 1 of this invention was implanted into an experimental rabbit. Detailed Implementation

[0036] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Unless otherwise stated, all raw materials and reagents used in this invention are commercially available or can be prepared by known methods.

[0038] Preparation Example 1

[0039] The preparation method of bioceramic microparticles specifically includes the following processes:

[0040] Weigh out 54.01g of hydroxyapatite, 126.23g of white calcium silicate, 180g of deionized water and 27.52g of composite binder (made by mixing and dispersing 20g of polyvinylpyrrolidone and 0.5g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min), mix them evenly, then adjust the pH to 8.5, and then put them into a ball mill jar. Ball mill them at 25℃ and 500r / min for 5h. After ball milling, put them into a vacuum drying oven and dry them at 55℃ for 20h to obtain submicron ceramic powder with a particle size of 0.62μm.

[0041] Weigh 179.98g of submicron ceramic powder and 393.14g of deionized water, mix and stir evenly to prepare a spray slurry;

[0042] The spray slurry is fed into a spray dryer and sprayed at a high temperature of 220°C to obtain bioceramic microparticle green bodies.

[0043] Bioceramic microparticle preforms were sintered at 1250℃ for 1 hour, and then naturally cooled to room temperature. The preforms were then sieved to obtain bioceramic microparticles with a particle size range of 10–70 μm. The bioceramic microparticles were characterized by scanning electron microscopy, and the results are as follows: Figure 1 As shown, the bioceramic microparticles have wrinkled and concave surfaces, giving them an overall wrinkled fruit-like appearance.

[0044] Preparation Example 2

[0045] The preparation method of bioceramic microparticles specifically includes the following processes:

[0046] Weigh out 53.24g of hydroxyapatite, 147.12g of β-tricalcium phosphate, 62.99g of white calcium silicate, 270g of deionized water, and 31.52g of composite binder (made by mixing and dispersing 20g of polyvinyl alcohol and 1g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min). Mix them evenly, then adjust the pH to 8.5, and then put them into a ball mill jar. Ball mill them at 30℃ and 600r / min for 6h. After ball milling, put them into a vacuum drying oven and dry them at 55℃ for 20h to obtain submicron ceramic powder with a particle size of 0.53μm.

[0047] Weigh 183.44g of submicron ceramic powder and 358.52g of deionized water, mix and stir evenly to prepare a spray slurry;

[0048] The spray slurry is fed into a spray dryer and sprayed at a high temperature of 240°C to obtain bioceramic microparticle green bodies.

[0049] Bioceramic microparticle preforms were sintered at 1400℃ for 2 hours, and then naturally cooled to room temperature. The preforms were then sieved to obtain bioceramic microparticles with a particle size range of 20–50 μm. The bioceramic microparticles were characterized by scanning electron microscopy, and the results are as follows: Figure 2 As shown, the bioceramic microparticles have wrinkled and concave surfaces, giving them an overall wrinkled fruit-like appearance.

[0050] Preparation Example 3

[0051] The preparation method of bioceramic microparticles specifically includes the following processes:

[0052] The composite binder in Preparation Example 2 (made by mixing and dispersing 20g of polyvinyl alcohol and 1g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min) was replaced with a composite binder (made by mixing and dispersing 20g of polyvinyl alcohol and 5g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min), resulting in ceramic powder with a particle size of 4.7μm; the rest of the preparation process was the same as in Preparation Example 2.

[0053] The bioceramic microparticles were characterized by scanning electron microscopy. The microparticles had a smooth surface without wrinkles or depressions, and were not wrinkled. Based on the absence of wrinkled fruit-like texture, subsequent experimental tests showed that the prepared composite material performed poorly in cell adhesion, proliferation, and differentiation, which was not conducive to promoting tissue regeneration. This may be because although dopamine hydrochloride can oxidize and self-polymerize to form viscous polydopamine, excessive dosage can easily lead to severe particle agglomeration during the grinding process, which is not conducive to the preparation of wrinkled bioceramic microparticles, and thus affects the relevant activity properties of the final prepared composite material.

[0054] Preparation Example 4

[0055] The preparation method of bioceramic microparticles specifically includes the following processes:

[0056] Weigh out 53.24g of hydroxyapatite, 147.12g of β-tricalcium phosphate, 62.99g of white calcium silicate, 270g of deionized water, and 31.52g of composite binder (made by mixing and dispersing 20g of polyvinyl alcohol and 1g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min). Mix them evenly, then adjust the pH to 8.5, and then put them into a ball mill jar. Ball mill them at 30℃ and 1000r / min for 10h. After ball milling, put them into a vacuum drying oven and dry them at 55℃ for 20h to obtain submicron ceramic powder with a particle size of 0.17μm. The rest of the preparation process is the same as in Preparation Example 2.

[0057] The bioceramic microparticles were characterized by scanning electron microscopy. The microparticles had a smooth surface without wrinkles or depressions, and were not wrinkled. Based on the absence of wrinkled fruit-like texture, subsequent experimental tests showed that the prepared composite material performed poorly in cell adhesion, proliferation, and differentiation, which was not conducive to promoting tissue regeneration. This may be because the ball milling mixing reaction was too long, which may have caused the particle size of the submicron ceramic powder to be excessively reduced. In this system, when it was mixed with deionized water to prepare the spray slurry, it was more likely to agglomerate, which was not conducive to the preparation of wrinkled fruit-like bioceramic microparticles, and thus affected the relevant activity properties of the final prepared composite material.

[0058] Preparation Example 5

[0059] The preparation method of bioceramic microparticles specifically includes the following processes:

[0060] The composite binder in Preparation Example 2 (made by mixing and dispersing 20g of polyvinyl alcohol and 1g of dopamine hydrochloride in an anaerobic environment with an ultrasonic power of 400W for 15min) was replaced with single polyvinyl alcohol to obtain submicron ceramic powder with a particle size of 0.59μm; the rest of the preparation process was the same as in Preparation Example 2.

[0061] The bioceramic microparticles were characterized by scanning electron microscopy. The microparticles had a smooth surface without wrinkles or depressions, and were not wrinkled. Based on the absence of wrinkled fruit-like texture, subsequent experimental tests showed that the prepared composite material performed poorly in cell adhesion, proliferation, and differentiation, which was not conducive to promoting tissue regeneration. This may be because, although the single binder in this system could bond calcium phosphate and magnesium silicate, the bonding effect was poor, which weakened the mixing of the two and was not conducive to the preparation of wrinkled bioceramic microparticles, thus affecting the relevant bioactive properties of the final composite material.

[0062] Preparation Example 6

[0063] The preparation method of bioceramic microparticles specifically includes the following processes:

[0064] Weigh out 45g of hydroxyapatite, 55g of white calcium silicate, 270g of deionized water, and 31.52g of composite binder (made by mixing and dispersing 20g of polyvinyl alcohol and 1g of dopamine hydrochloride in an oxygen-free environment with an ultrasonic power of 400W for 15min). Mix them evenly, then adjust the pH to 8.5, and then put them into a ball mill jar. Ball mill them at 30℃ and 600r / min for 6h. After ball milling, put them into a vacuum drying oven and dry them at 55℃ for 20h to obtain submicron ceramic powder with a particle size of 0.48μm. The rest of the preparation process is the same as in Preparation Example 2.

[0065] The bioceramic microparticles were characterized by scanning electron microscopy. The microparticles had a smooth surface without wrinkles or depressions, and were not wrinkled. Based on the absence of wrinkled fruit-like texture, subsequent experimental tests showed that the prepared composite material performed poorly in cell adhesion, proliferation, and differentiation, which was not conducive to promoting tissue regeneration. This may be because the amount of calcium phosphate and magnesium silicate used in this system was low, which was not conducive to the preparation of wrinkled bioceramic microparticles, and thus affected the relevant activity properties of the final prepared composite material.

[0066] Preparation Example 7

[0067] The preparation method of microfiber gel specifically includes the following steps:

[0068] Bovine decellularized dermal matrix collagen membrane material was obtained by enzymatic hydrolysis of bovine dermis through a series of degreasing and decellularization steps.

[0069] Then, 2g of bovine decellularized dermal matrix collagen membrane material was placed in 50mL of 0.1% acetic acid aqueous solution and soaked for 1h. After soaking, the bovine decellularized dermal matrix collagen membrane material was taken out and the solution floating on the surface of the bovine decellularized dermal matrix collagen membrane material was drained to obtain pretreated bovine decellularized dermal matrix collagen membrane material.

[0070] 30.02g of pretreated bovine decellularized dermal matrix collagen membrane material was mixed with 110mL of deionized water and placed in a crusher to be crushed for 3h until it reached a solution state. Then, it was filtered through a 300-mesh sieve to obtain microfiber gel.

[0071] Preparation Example 8

[0072] The preparation method of microfiber gel specifically includes the following steps:

[0073] The 1-hour soaking in 0.1% acetic acid aqueous solution in Preparation Example 7 was replaced with a 2-hour soaking in 1% acetic acid aqueous solution.

[0074] Example 1

[0075] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0076] 10.32g of the bioceramic microparticles prepared in Preparation Example 1 were weighed and slowly added to 191.51g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0077] Example 2

[0078] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0079] 31.03g of the bioceramic microparticles prepared in Preparation Example 2 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0080] Comparative Example 1

[0081] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0082] 31.03g of the bioceramic microparticles prepared in Preparation Example 3 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0083] Comparative Example 2

[0084] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0085] 31.03g of the bioceramic microparticles prepared in Preparation Example 4 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0086] Comparative Example 3

[0087] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0088] 31.03g of the bioceramic microparticles prepared in Preparation Example 5 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0089] Comparative Example 4

[0090] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0091] 31.03g of the bioceramic microparticles prepared in Preparation Example 6 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0092] Comparative Example 5

[0093] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0094] 31.03g of the bioceramic microparticles prepared in Preparation Example 2 were slowly added to 176.78g of the microfiber gel obtained in Preparation Example 8. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0095] Comparative Example 6

[0096] A method for preparing a wrinkled fruit-like bioceramic microparticle-based composite material specifically includes the following steps:

[0097] 58.08g of the bioceramic microparticles prepared in Preparation Example 2 were slowly added to 118.85g of the microfiber gel obtained in Preparation Example 7. The mixture was then placed in a homogenizer, and the homogenization pressure was controlled at 15MPa and the homogenization speed at 1300r / min. The mixture was subjected to high-pressure homogenization for 9min to fully disperse the bioceramic microspheres in the microfiber gel and obtain the composite material.

[0098] (1) Performance testing of soft tissue repair patch products:

[0099] The viscosity characteristics of the composite materials prepared in Examples 1-2 and Comparative Examples 1-6 under different temperature conditions were investigated, and the results are as follows: Figure 3 As shown in the figure. The experiment used a rotational viscometer to measure the viscosity of the gel samples at a uniform shear rate. By testing the rheological behavior of the composite material at a series of temperature points (from 5°C to 40°C), we found that Examples 1 and 2 had the highest viscosity near human body temperature, while the viscosity decreased significantly at lower temperatures. This phenomenon may be related to the enhanced interaction of the gel carrier near physiological temperature, resulting in a more compact composite structure and thus increasing its viscosity. Conversely, at temperatures far from human body temperature, the intermolecular interactions weaken, the composite structure becomes looser, and the viscosity decreases accordingly. These results provide important theoretical basis for the injection of the drug and its function under physiological conditions.

[0100] (2) Osteogenic / fibrogenic evaluation of bioceramic microparticles:

[0101] Mesenchymal stem cell (MSCs) were seeded in 6-well plates and cultured in a CO2 incubator at 37°C using complete culture medium containing the composite materials from Examples 1-2 and Comparative Examples 1-4. On day 3, cells were digested with 0.25% (1×) trypsin and seeded entirely into T25 culture flasks. On day 6, cells were digested and seeded into T75 culture flasks. On day 9, cells were digested and collected. 1 mL of the cultured cells and 1 mL of MSCs (cell concentration approximately 5 × 10⁻⁶ cells) were taken. 5 Cells (cells / mL) were added to each tube with 250 μL of cell permeabilization buffer and incubated in the dark for 20 minutes. After permeabilization, rabbit anti-human FSP-1 and rabbit ALP polyclonal antibodies were added, and incubation was continued in the dark for 1 hour. Then, 100 μL of diluted secondary antibody (1:200, v / v) was added to each sample tube and incubated in the dark for 30 minutes. Finally, 200 μL of antibody preservation solution was added to resuspend the cells, and flow cytometry was used for analysis. FSP-1 protein is a fibroblast-specific protein 1, commonly used to label fibroblasts; ALP is alkaline phosphatase, a widely recognized marker of osteoblast activity. Results are as follows: Figure 4As shown, the expression of FSP-1 protein and ALP in MSCs induced by composite materials was increased, indicating that MSCs have the potential to differentiate into fibroblasts and osteoblasts under the induction of composite materials.

[0102] (3) Evaluation of the tissue regeneration performance of the composite material prepared in Example 1:

[0103] After general anesthesia, a longitudinal skin incision of approximately 3 cm was made at the shoulder joint of the experimental rabbits. The deltoid muscle was bluntly dissected to expose the insertion of the supraspinatus tendon on the greater tubercle. Subsequently, the supraspinatus tendon was sharply severed, and a 0.3 cm × 0.3 cm section of tendon tissue was removed to establish a rotator cuff injury model (e.g., Figure 5 (As shown). The composite material prepared in Example 1 was used to bridge and repair tendon injuries. Specifically, the composite material was directly injected into the injured area of ​​the tendon to achieve tendon repair. Anatomical observation and staining two months post-surgery showed (e.g.) Figure 6 As shown in the figure, the regenerated collagen fibers are arranged in an orderly manner, and the number of tendon cells has increased, indicating that the tendon is highly mature.

[0104] The embodiments described above, along with the accompanying drawings, have provided a detailed explanation of the technical solutions and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Various changes and modifications can be made to the present invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed.

Claims

1. A wrinkled, fruit-like bioceramic microparticle-based composite material, characterized in that, The composite material consists of 5% to 15% bioceramic microparticles and 85% to 95% microfiber gel by mass fraction. The preparation method of the bioceramic microparticles includes the following steps: Submicron ceramic powder was obtained by ball milling and drying a mixture of calcium phosphate, magnesium silicate, water, and composite binder. Submicron ceramic powder and deionized water are mixed and stirred to form a spray slurry; Bioceramic microparticle preforms are obtained by high-temperature spray granulation of the spray slurry at 220℃~240℃; After the bioceramic microparticle green body is sintered at a high temperature of 1250℃~1400℃ for 1h~2h, bioceramic microparticles with a particle size of 10μm~70μm are obtained by screening. The calcium phosphate includes hydroxyapatite and / or β-tricalcium phosphate; The magnesium silicate includes white calcium silicate; The composite adhesive is composed of polyvinylpyrrolidone and dopamine hydrochloride in a weight ratio of 40:1~2 or polyvinyl alcohol and dopamine hydrochloride in a weight ratio of 40:1~2. The weight ratio of calcium phosphate: magnesium silicate: water: composite adhesive is 54~201:62~127:180~270:27~32; The conditions for the ball milling process include a ball milling temperature of 25℃~30℃, a ball milling speed of 500r / min~600r / min, a ball milling time of 5h~6h, and a ball milling pH of 8.

5.

2. The wrinkled fruit-like bioceramic microparticle-based composite material according to claim 1, characterized in that, The weight ratio of the submicron ceramic powder to deionized water is 179~184:358~394.

3. The wrinkled fruit-like bioceramic microparticle-based composite material according to claim 1, characterized in that, The preparation method of the microfiber gel includes the following steps: Bovine decellularized dermal matrix collagen membrane material was obtained by degreasing and decellularizing bovine dermis. 2g of bovine decellularized dermal matrix collagen membrane material was soaked in 50mL of 0.1% acetic acid aqueous solution for 1h, and then drained to obtain pretreated bovine decellularized dermal matrix collagen membrane material. Pretreated bovine decellularized dermal matrix collagen membrane material was mixed with deionized water and then crushed through a 300-mesh sieve to obtain microfiber gel.

4. The wrinkled fruit-like bioceramic microparticle-based composite material according to claim 3, characterized in that, The weight ratio of the pretreated bovine decellularized dermal matrix collagen membrane material to deionized water is 30:

110.

5. A method for preparing a wrinkled, fruit-like bioceramic microparticle-based composite material as described in any one of claims 1 to 4, characterized in that, The preparation method includes the following steps: The composite material is obtained by mixing 5% to 15% bioceramic microparticles and 85% to 95% microfiber gel by weight percentage and then homogenizing at high speed.

6. The application of a wrinkled bioceramic microparticle-based composite material as described in any one of claims 1 to 4, or a composite material prepared by the preparation method described in claim 5, in the preparation of drugs for soft tissue repair.

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