Particle spraying and fiber electrostatic spinning combined 3D (three-dimensional) fiber scaffold as well as preparation method and application thereof in dermis / cartilage repair

Abstract

The invention provides a particle spraying and fiber electrostatic spinning combined 3D fiber scaffold, a preparation method of the 3D fiber scaffold and application of the 3D fiber scaffold in dermis / cartilage repair. The 3D fiber scaffold comprises an electrospinning fiber membrane and solid particles distributed in the electrospinning fiber membrane. And the solid particles are distributed on the surfaces of the electrospun fibers in the electrospun fiber membrane. The fiber membrane has ultrahigh mechanical strength, and pores among fibers of the electrostatic spinning membrane are also increased by the inorganic particles; particularly, the size of interfibrous pores can be selectively adjusted through the particle size of the inorganic particles, and the infiltration and migration of dermal cells and cartilage cells in the scaffold in the dermal repair and cartilage repair processes can be effectively enhanced by increasing the pores, so that an extracellular matrix is formed and remodeled more quickly; the dermis structure or the cartilage structure can be reconstructed in a short time, and the repairing effect is finally enhanced.

Description

Technical Field

[0001] This application belongs to the technical field of dermal / cartilage repair materials, and particularly relates to a microparticle spraying combined with fiber electrospinning 3D fiber scaffold, its preparation method and its application in dermal / cartilage repair. Background Technology

[0002] Currently, the fibrous membrane materials used in dermal / cartilage repair materials are generally single-layer structures, but some are double-layer or multi-layer structures.

[0003] The main methods for preparing double / multi-layer composite electrospun fiber membranes include the following: (1) directly electrospun a second electrospun layer in situ on the first electrospun layer; (2) spray an adhesive layer onto the first electrospun layer using air spraying or electrostatic spraying, and then composite an electrospun fiber membrane on it, or electrospun a fiber membrane in situ on it and then press it to obtain a double-layer composite electrospun fiber membrane; (3) brush an adhesive layer onto the first electrospun layer using a brushing method, and then composite an electrospun fiber membrane on it, or electrospun a fiber membrane in situ on it and then press it to obtain a double-layer composite electrospun fiber membrane.

[0004] The aforementioned preparation methods are not only complex in process, but also present numerous problems when the prepared fibers are used in artificial dermal and cartilage repair materials. For example, the interfacial bonding strength of electrospun bilayer / multilayer scaffolds is insufficient, leading to easy separation. Improving interlayer adhesion relies on adhesives, which are complex and costly. Without additional adhesives, the bonding force between fiber membrane layers is poor. When adhesives (usually liquid) are used, a distinct adhesive layer exists between layers, potentially significantly impacting the permeability and porosity of the fiber membrane, ultimately affecting the repair effect of the composite fiber membrane. Insufficient fiber strength manifests as weak tensile strength, making it prone to breakage under tangential forces. Fibers prepared using electrospinning methods typically have diameters ranging from micrometers to sub-millimeters. These fine fibers aggregate into a fiber membrane with small pores. Although this relatively dense fiber membrane has high tensile strength, the small internal pores of the fiber scaffold make it difficult for cells and cell fluid to infiltrate the scaffold, hindering the perfect synchronization between scaffold degradation and new tissue generation. In addition, the smaller diameter of electrospun fibers and the smaller gaps between interlayer fibers are not conducive to the effective infiltration and growth of dermal cells or chondrocytes.

[0005] Therefore, providing a fibrous membrane material with higher fiber porosity that is beneficial for rapid dermal / cartilage repair remains a problem to be solved. Summary of the Invention

[0006] This application provides a microparticle spraying combined with electrospinning 3D fiber scaffold, its preparation method, and its application in dermal / cartilage repair, to solve the problems existing in related technologies. The technical solution is as follows: In a first aspect, embodiments of this application provide a microparticle spraying combined with electrospun fiber 3D fiber scaffold, comprising an electrospun fiber membrane and solid particles distributed within the electrospun fiber membrane; the solid particles are distributed on the surface of the electrospun fiber filaments within the electrospun fiber membrane.

[0007] In one embodiment, the content of solid particles is 10-50% of the weight of the electrospun fiber membrane.

[0008] In one embodiment, the porosity of the electrospun fiber membrane is 5-40%.

[0009] In one embodiment, the material of the electrospun fiber membrane is one or a combination of two or more of polyglycolic acid, polylactic acid, or polyurethane.

[0010] In one embodiment, the solid particles are one or a combination of two or more of hydroxyapatite, calcium sulfate, calcium phosphate, or calcium carbonate.

[0011] In one embodiment, the particle size of the solid particles is 1-10 μm.

[0012] Secondly, embodiments of this application provide a method for preparing a 3D fiber scaffold using a combination of microparticle spraying and electrospinning, comprising the following steps: During electrospinning, an organic solution containing solid particles is sprayed onto the electrospinning fiber to obtain an electrospinning membrane doped with particles; after removing the organic solvent, the microparticle-sprayed combined fiber electrospinning 3D fiber scaffold is obtained.

[0013] In one embodiment, the electrospinning solution is prepared by dissolving the material of the electrospinning fiber membrane in N,N-methylenebisacrylamide to prepare the electrospinning solution.

[0014] In one embodiment, the concentration of the electrospun fiber solution is 10-15%wt.

[0015] In one embodiment, the organic solution of the solid particles is prepared by dispersing the solid particles in N,N-methylenebisacrylamide.

[0016] In one embodiment, the concentration of the organic solution containing the solid particles is 55%-70%.

[0017] In one embodiment, the electrospun fiber preparation conditions are as follows: the spinning needle is 21G, the temperature of the spinning environment is 35-40℃, the relative humidity is 35-45%rh, the distance between the spinning needle and the collector is 20 cm, the spinning solution is injected at a rate of 1 mL / h, and the positive electrode voltage of the needle is set to +16 kV.

[0018] In one embodiment, the organic solution spraying flow rate for the solid particles is 2-5 mL / min.

[0019] In one embodiment, the process of removing organic solvents involves placing an electrospun membrane doped with particles in a vacuum oven to remove the organic solvents.

[0020] Thirdly, embodiments of this application provide the application of microparticle spraying combined with fiber electrospinning 3D fiber scaffolds as dermal / cartilage repair materials.

[0021] The advantages or beneficial effects of the above technical solutions include at least the following: This application presents a microparticle-sprayed combined electrospun 3D fiber scaffold, comprising an electrospun fiber membrane and solid particles distributed within the electrospun fiber membrane; the solid particles are distributed on the surface of the electrospun fiber filaments within the electrospun fiber membrane. It not only possesses extremely high mechanical strength, but the inorganic particles also increase the porosity between the fibers of the electrospun film; specifically, the size of the interfiber pores can be selectively adjusted through the particle size of the inorganic particles. Increased porosity effectively enhances the infiltration and migration of dermal and cartilage cells within the cells during dermal and cartilage repair processes, ultimately enhancing the repair effect.

[0022] In the material preparation method used in this application, when an organic solution containing inorganic particles is sprayed onto a fiber membrane, the organic solution can partially dissolve the surface of the electrospun fibers. At this time, the fiber material in the solution acts as an adhesive to bond the particles to the two adjacent fibers, which can enhance the integrity of the fiber membrane and ultimately enhance the mechanical strength of the fiber membrane to a certain extent.

[0023] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of this application will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description

[0024] In the accompanying drawings, unless otherwise specified, the same reference numerals throughout the various drawings denote the same or similar parts or elements. These drawings are not necessarily drawn to scale. It should be understood that these drawings depict only some embodiments disclosed in this application and should not be construed as limiting the scope of this application.

[0025] Figure 1SEM images of the fiber membranes prepared in Example 1 and Comparative Example 2 are shown; the left image is the fiber membrane of Example 1, and the right image is the fiber membrane prepared in Comparative Example 2. Figure 2 Figure 1 shows the cell layer weight ratio in the scaffold after culturing fibroblasts in the fibrous membranes of each embodiment / comparative example for 4 days. Figure 3 This is a schematic diagram of the structure of the microparticle spraying combined with fiber electrospinning 3D fiber scaffold of this application and the scaffold of Comparative Examples 1-2. Detailed Implementation

[0026] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of this application. Therefore, the drawings and description are considered to be exemplary in nature and not restrictive.

[0027] This application provides a microparticle-sprayed combined electrospun 3D fiber scaffold, comprising an electrospun fiber membrane and solid particles distributed within the electrospun fiber membrane; the solid particles are distributed on the surface of the electrospun fiber filaments within the electrospun fiber membrane. A schematic diagram is shown below. Figure 3 As shown in a).

[0028] The electrospun 3D fiber scaffold of this application is a composite bilayer / multilayer 3D fiber membrane material. As a dermal / cartilage repair material, it uses microparticles to overcome the technical shortcomings of small inter-fiber porosity in traditional electrospun films. This 3D fiber membrane not only possesses ultra-high mechanical strength (such as tensile properties), but more importantly, it has adjustable inter-fiber porosity (effectively adjustable by controlling the size of the sprayed particles). By adding particles to the 3D fiber membrane, not only can the inter-fiber friction, strength, and integrity be increased, but the fiber membrane also exhibits a degradation rate and regeneration-promoting factor release effect that matches the regeneration cycle.

[0029] When the 3D fiber membrane prepared using this patent is applied to dermal and cartilage repair, it is more conducive to the migration and infiltration of dermal cells or chondrocytes into the internal space of the fiber membrane, rather than being limited to migration and infiltration on the upper and lower surfaces of the fiber membrane. Thanks to this three-dimensional cell migration, the extracellular matrix is ​​formed and remodeled more quickly, and the dermal or cartilage structure can be reconstructed in a short time.

[0030] As one implementation method, the content of solid particles is 10-50% of the weight of the electrospun fiber membrane.

[0031] As one implementation method, the porosity of the electrospun fiber membrane is 5-40%.

[0032] In one embodiment, the electrospun fiber membrane is made of one or more of polyglycolic acid, polylactic acid, or polyurethane. Polyglycolic acid degrades rapidly; polyurethane, especially medical-grade polyurethane, is highly hydrophobic, which is not conducive to cell adhesion, but it has high strength and a slower degradation rate.

[0033] In one embodiment, the solid particles are inorganic powders or organic microspheres; in this embodiment, the inorganic powder is one or a combination of two or more of hydroxyapatite, calcium sulfate, calcium phosphate, or calcium carbonate. The aforementioned calcium-containing inorganic particles are commonly used fillers in the art.

[0034] The sprayed particles can be bioactive, such as hydroxyapatite or biodegradable microspheres loaded with growth factors. These particles can not only enhance the structure and form large pores between fibers, but also act as stimulating factors to stimulate cell migration and growth, ultimately promoting collagen remodeling. For example, hydroxyapatite releases calcium ions to stimulate osteoblast differentiation (hydroxyapatite can improve bone integration and results).

[0035] Furthermore, the solid particles may be particles loaded with growth factors or other bioactive factors, or particles that can degrade to produce factors that promote cell / tissue regeneration.

[0036] In one embodiment, the solid particles have a particle size of 1-10 μm. They can be prepared by mechanical pulverization.

[0037] This application provides a method for preparing a 3D fiber scaffold using a combination of microparticle spraying and electrospinning, comprising the following steps: During electrospinning, an organic solution containing solid particles is sprayed onto the electrospinning fiber to obtain an electrospinning membrane doped with particles. After removing the organic solvent, the microparticle-sprayed combined fiber electrospinning 3D fiber scaffold is obtained.

[0038] In this application, during electrospinning, an organic solvent containing solid particles is sprayed onto the electrospinning fiber region simultaneously with fiber formation and film formation. These solid particles adhere to the fiber surface and, as the fiber weaves and forms the film, distribute into the interior of the fiber membrane. This achieves solid particle incorporation between the fibers. The electrospun fibers result in a membrane with extremely high mechanical strength. The presence of solid particles, adhering to the fiber surface rather than being completely encapsulated by the fiber material, utilizes the particle volume to increase porosity between fibers; it also increases inter-fiber friction, strength, and overall integrity, and enables the fiber membrane to exhibit a degradation rate and regeneration-promoting factor release effect that matches the regeneration cycle.

[0039] As one embodiment, the electrospinning solution is prepared by dissolving the material of the electrospinning fiber membrane in N,N-methylenebisacrylamide to form the electrospinning solution. Using N,N-methylenebisacrylamide as a solvent provides good solubility and facilitates removal.

[0040] In one embodiment, the concentration of the electrospun fiber solution is 10-15%wt.

[0041] As one embodiment, the organic solution of the solid particles is prepared by dispersing the solid particles in N,N-methylenebisacrylamide.

[0042] As one implementation method, the concentration of the organic solution containing the solid particles is 55%-70%.

[0043] As one embodiment, the electrospun fiber preparation conditions are as follows: the spinning needle is 21G, the temperature of the spinning environment is 35-40℃, the relative humidity is 35-45%rh, the distance between the spinning needle and the collector is 20 cm, the spinning solution is injected at a rate of 1 mL / h, and the positive electrode voltage of the needle is set to +16 kV.

[0044] As one implementation method, the flow rate of the organic solution sprayed onto the solid particles is 2-5 mL / min.

[0045] As one implementation method, the process of removing organic solvents involves placing an electrospun membrane doped with particles in a vacuum oven to remove the organic solvents.

[0046] The microparticle spraying combined with electrospinning of fibers in this application results in a 3D fiber scaffold that can be used as a dermal / cartilage repair material. The following is a further explanation using specific embodiments.

[0047] Example 1 (1) Preparation of electrospinning solution: Weigh 125g of medical polyurethane (PU) and place it in 875g of N,N-methylenebisacrylamide solution. Stir at room temperature to dissolve it and prepare a 12.5%wt PU electrospinning solution. (2) Preparation of spraying solution: Weigh 100g of hydroxyapatite powder (particle size between 1-10 μm), add 60g of N,N-methylenebisacrylamide solution, and stir thoroughly to mix the powder and solution evenly; (3) Electrospun fiber preparation conditions: the spinning needle is 21G, the temperature of the spinning environment is 35-40℃, the relative humidity is 35-45%rh, the distance between the spinning needle and the collector is 20 cm, the positive electrode voltage of the needle is set to +16 kV, and the electrospinning time is 5 min. (4) Conditions for preparing the spray coating: Use an air spraying machine. Before spraying, shake the spraying liquid thoroughly. The spraying time is 5 min. (5) A PU electrospun film was prepared by electrospinning. During electrospinning, hydroxyapatite powder suspended in N,N-methylenebisacrylamide solution was sprayed onto the electrospun fiber area by air spraying. The electrospinning solution injection rate was 1 mL / h, and the air spraying flow rate was set to 3 mL / min. After completion, the above-mentioned electrospun film doped with particles was placed in a vacuum oven and dried for 48 h to remove excess organic solvent, thus obtaining 3D fiber film A.

[0048] Example 2 Compared to Example 1, in this example, the electrospinning solution injection rate is 2 mL / h, the air spraying flow rate is set to 3 mL / min, and the remaining steps are the same as in Example 1, resulting in 3D fiber membrane B.

[0049] Example 3 Compared to Example 1, in this example, the electrospinning solution injection rate is 3 mL / h, the air spraying flow rate is set to 3 mL / min, and the remaining steps are the same as in Example 1, resulting in a 3D fiber membrane C.

[0050] Example 4 Compared to Example 1, in this example, the electrospinning solution injection rate is 1 mL / h, the air spraying flow rate is set to 2 mL / min, and the remaining steps are the same as in Example 1, resulting in a 3D fiber membrane D.

[0051] Example 5 Compared to Example 1, in this example, the electrospinning solution injection rate is 1 mL / h, the air spraying flow rate is set to 4 mL / min, and the remaining steps are the same as in Example 1, resulting in a 3D fiber membrane E.

[0052] Example 6 Compared to Example 1, in this example, the electrospinning solution injection rate is 1 mL / h, the air spraying flow rate is set to 5 mL / min, and the remaining steps are the same as in Example 1, resulting in a 3D fiber membrane F.

[0053] Example 7 Compared to Example 1, the electrospinning and air spraying time in this example is 2 minutes, and the remaining steps are the same as in Example 1, to obtain a 3D fiber membrane G.

[0054] Example 8 Compared to Example 1, the electrospinning and air spraying time in this example is 10 minutes, and the remaining steps are the same as in Example 1, to obtain a 3D fiber membrane H.

[0055] Example 9 Compared to Example 1, the particles in the spray solution in this example are calcium sulfate powder (particle size between 1-20 μm), and the remaining steps are the same as in Example 1, to obtain 3D fiber membrane I.

[0056] Comparative Example 1 Compared to Example 1, this example omits the air spraying component, consisting only of a simple electrospinning step. The remaining steps are the same as in Example 1, resulting in a comparative 3D fiber membrane 1. The structural diagram is shown below. Figure 3 b) Comparative Example 2 Compared to Example 1, in this example, the electrospinning and air spraying steps are performed separately. First, an electrospinned film is obtained on the substrate by electrospinning for 5 minutes (electrospinning solution injection rate is 1 mL / h). Then, a particulate solution is sprayed onto the electrospinned film by air spraying for 5 minutes (air spraying flow rate is set to 3 mL / min). Finally, another electrospinned film is electrospinned on the particulate layer for 5 minutes to obtain a contrast 3D fiber membrane 2 with a sandwich structure (fiber layer-particulate layer-fiber layer). The structural diagram is shown below. Figure 3 As shown in c).

[0057] Fiber membrane testing (1) The fiber membranes prepared in Example 1 and Comparative Example 2 of this application were observed by SEM. The SEM images of the fiber membranes in Example 1 and Comparative Example 2 are shown below. Figure 1 As shown in the left and right images.

[0058] from Figure 1 As can be seen, in the fiber membrane prepared in Example 1, solid particles are attached to the surface of the fiber filaments, and these solid particles are uniformly distributed between the fiber filaments throughout the entire fiber membrane. Furthermore, the pore size of the fiber membrane prepared in Example 1 is significantly larger than that of the fiber membrane prepared in Comparative Example 2.

[0059] (2) 3D fiber membrane thickness measurement Take the prepared fiber membrane and use a thickness gauge (accuracy 0.1 mm) to measure 10 random points on the fiber membrane. Record the measured data, calculate the average value and error. The results are shown in Table 1.

[0060] (3) Measurement of 3D fiber membrane particle content The 3D fiber membrane obtained by electrospinning and particle spraying was weighed to obtain mass m1. At the same time, the fiber membrane obtained under the same electrospinning conditions was weighed to obtain mass m2. The particle content of the 3D fiber membrane was (m1-m2) / m1×100%. Three samples were taken for each example and comparative example for testing, and the average value and error were taken. The results are shown in Table 1.

[0061] (4) Measurement of porosity of 3D fiber membrane The 3D fiber membrane obtained by combined electrospinning and particle spraying was dimensionally measured, and its volume V1 was calculated. The volume V2 of the sprayed particles was calculated by measuring the remaining solution volume. Simultaneously, the volume V3 of the fiber membrane obtained under the same electrospinning conditions was measured using the water volume method. Therefore, the porosity of the 3D fiber membrane was calculated as [1 - (V2 + V3) / V1] × 100%. Three samples were tested for each example and comparative example, and the average value and error were taken. The results are shown in Table 1.

[0062] (5) 3D fiber membrane fiber peeling force determination The electrospun fiber membrane (cut into rectangular strips 1 cm wide) was clamped at both ends by two clamps of a tensile testing machine. The two layers of fiber membrane were then pulled apart at a speed of 5 cm / min. The maximum force detected by the tensile testing machine during the pulling process was recorded, which is the interlayer bonding force of the fiber membrane. Three samples were tested for each example and comparative example, and the average value and error were taken. The results are shown in Table 1.

[0063] (6) 3D fiber membrane tensile strength test: The fiber membrane was cut into strips 5 cm long and 1 cm wide. The two ends of the fiber membrane were clamped by the upper and lower clamps of a tensile testing machine. The fiber membrane was then stretched at a rate of 5 cm / min. The maximum force detected by the tensile testing machine during the stretching process was recorded, which is the tensile strength of the fiber membrane. Three samples were tested for each example and comparative example, and the average value and error were taken. The results are shown in Table 1.

[0064] (7) 3D Fiber Membrane Cell Migration and Proliferation Activity Evaluation Experiment The fiber membranes were cut into rectangles 2cm long and 2cm wide, sterilized using autoclaving, and then placed in culture medium (fibroblast density 1×10⁻⁶). 5 The cells were cultured in 6cm culture dishes containing approximately 1 / mL of the sample and placed in a constant-temperature cell culture incubator for 4 days. After 4 days, the membrane was removed, washed three times with PBS, and then fibroblasts on the membrane were digested with trypsin. The cells were weighed, and the cell weight ratio of each example was calculated using the sample from Comparative Example 1 as a baseline. Three samples were taken for each example and comparative example for testing, and the average value and error were calculated. The results are as follows: Figure 2 As shown.

[0065] Table 1

[0066] from Figure 1As can be seen from Table 1, the 3D fiber membrane provided in this application has a higher porosity than the fiber membrane obtained by traditional electrospinning. This is because the sprayed particles are embedded between the fibers, increasing the longitudinal gap between the electrospun fiber membrane layers. As the particle spraying flow rate increases, this gap gradually increases (for example, in Example 5, when the particle spraying flow rate increases from 3 mL / min in the example to 4 mL / min, the porosity increases to 27±5%). It is worth noting that as the spraying flow rate further increases, the porosity of the fiber membrane decreases (for example, in Example 6, when the particle spraying flow rate further increases to 5 mL / min, the porosity decreases to 20±2%). This may be because too many particles will cause some particles to block the gaps between the transverse fibers, resulting in a slight decrease in the porosity of the fiber membrane.

[0067] Furthermore, as the flow rate of the electrospun fiber solution increases, the porosity of the fiber membrane will decrease significantly due to the lack of sufficient particle support for the fiber (for example, in Example 3, when the injection speed of the electrospun solution was increased from 1 mL / h in Example 1 to 3 mL / h, the porosity decreased to 12±3%).

[0068] In addition, adding a granular layer between the electrospun fiber membranes can improve the integrity and mechanical strength of the electrospun fiber membranes, mainly manifested in higher interfiber peeling force (from 0.1±0.05 N / cm in Comparative Example 1 to 3.7±1.2 N / cm in Example 63) and breaking strength (from 5.5±0.7 N / cm in Comparative Example 1 to 11.4±0.5 N / cm in Example 8).

[0069] from Figure 2 It can be seen that the increased porosity of the fiber membrane is conducive to the rapid migration and proliferation of fibroblasts, ultimately forming thicker and more numerous fibroblasts. In addition, when the sprayed particles are replaced with calcium sulfate particles (Example 9), the growth activity of fibroblasts is further improved. This may be because the sulfate ions released by the calcium sulfate particles during the degradation process have a higher fibroblast-promoting activity than the phosphate ions released during the degradation process of hydroxyapatite.

[0070] In summary, the 3D fiber membrane of this application can not only improve the problem of weak mechanical strength of traditional electrospun fiber membranes, but also significantly increase the porosity of the fiber membrane to further enhance the growth activity of fibroblasts in the fiber membrane scaffold, which is ultimately beneficial to dermal and cartilage repair.

[0071] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of those different embodiments or examples.

[0072] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "a plurality of" means two or more, unless otherwise explicitly specified.

[0073] The above description is merely a specific embodiment of this application, but the scope of protection of this application is not limited thereto. Any person skilled in the art can easily conceive of various variations or substitutions within the technical scope disclosed in this application, and these should all be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.

Claims

1. A microparticle spraying combined with electrospinning of fibers to create a 3D fiber scaffold, characterized in that, It includes an electrospun fiber membrane and solid particles distributed within the electrospun fiber membrane; the solid particles are distributed on the surface of the electrospun fiber filaments within the electrospun fiber membrane.

2. The microparticle spraying combined with electrospinning 3D fiber scaffold according to claim 1, characterized in that, The content of solid particles is 10-50% of the weight of the electrospun fiber membrane; the porosity of the electrospun fiber membrane is 5-40%.

3. The microparticle spraying combined with electrospinning 3D fiber scaffold according to claim 1, characterized in that, The material of the electrospun fiber membrane is one or a combination of two or more of polyglycolic acid, polylactic acid or polyurethane. The solid particles are one or more of hydroxyapatite, calcium sulfate, calcium phosphate, or calcium carbonate; the particle size of the solid particles is 1-10 μm.

4. The method for preparing a 3D fiber scaffold by microparticle spraying combined with electrospinning of fibers according to any one of claims 1-3, characterized in that, Includes the following steps: During electrospinning, an organic solution containing solid particles is sprayed onto the electrospinning fiber to obtain an electrospinning membrane doped with particles; after removing the organic solvent, the microparticle-sprayed combined fiber electrospinning 3D fiber scaffold is obtained.

5. The method for preparing a 3D fiber scaffold using microparticle spraying combined with electrospinning according to claim 4, characterized in that, The electrospinning solution is prepared by dissolving the material of the electrospinning fiber membrane in N,N-methylenebisacrylamide to prepare the electrospinning solution. The concentration of the electrospun fiber solution is 10-15%wt.

6. The method for preparing a 3D fiber scaffold using microparticle spraying combined with electrospinning according to claim 4, characterized in that, The organic solution of the solid particles was prepared by dispersing the solid particles in N,N-methylenebisacrylamide; the concentration of the organic solution of the solid particles was 55%-70%.

7. The method for preparing a 3D fiber scaffold using microparticle spraying combined with electrospinning according to claim 4, characterized in that, Electrospun fiber preparation conditions: the spinning needle was 21G, the temperature of the spinning environment was 35-40℃, the relative humidity was 35-45%rh, the distance between the spinning needle and the collector was 20 cm, the spinning solution was injected at a rate of 1 mL / h, and the positive electrode voltage of the needle was set to +16 kV.

8. The method for preparing a 3D fiber scaffold using microparticle spraying combined with electrospinning according to claim 4, characterized in that, The flow rate of the organic solution sprayed with solid particles is 2-5 mL / min.

9. The method for preparing a 3D fiber scaffold using microparticle spraying combined with electrospinning according to claim 4, characterized in that, The process of removing organic solvents involves placing the electrospun membrane doped with particles in a vacuum oven to remove the organic solvents.

10. The application of the microparticle spraying combined with electrospun fiber 3D fiber scaffold as a dermal / cartilage repair material according to any one of claims 1-3.

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