Fiber membrane for guiding periodontal tissue regeneration and method for preparing the same

Abstract

The application discloses a fibrous membrane for guiding periodontal tissue regeneration and a preparation method thereof, and belongs to the technical field of periodontal tissue regeneration. The fibrous membrane comprises a double-layer structure of a polylactic acid dense layer and a polylactic acid loose layer. The polylactic acid dense layer is compounded with sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs, which are used for barrier epithelial cell growth and release of the anti-inflammatory and antibacterial drugs. The polylactic acid loose layer is compounded with sodium hyaluronate microparticles loaded with bone regeneration promoting drugs, which are used for promoting osteoblast adhesion and release of the bone regeneration promoting drugs. The fibrous membrane is constructed by electrospinning technology and electrostatic spraying technology, and realizes the double treatment purposes of antibacterial isolation and osteogenesis guidance.

Description

Technical Field

[0001] This invention relates to the field of periodontal tissue regeneration technology, specifically to a guided tissue regeneration membrane for periodontal tissue regeneration and its preparation method. Background Technology

[0002] Periodontal regenerative medicine aims to achieve functional regeneration of periodontal attachments, and guided periodontal tissue regeneration (GTR) membranes are a core tool for achieving this goal.

[0003] However, existing technologies have the following drawbacks: First, most existing GTR membranes are single-layer structures or lack precise zoning designs, making it difficult to simultaneously meet the complex needs of blocking gingival epithelial cell ingrowth and promoting osteoblast proliferation, resulting in periodontal healing often leading to epithelial regeneration rather than functional bone regeneration. Secondly, existing electrospun GTR membranes typically use organic solvents in their preparation process. Many hydrophilic anti-inflammatory and antibacterial drugs have poor solubility in the organic phase, resulting in extremely low loading rates. Furthermore, bioactive molecules such as growth factors are easily deactivated under the high voltage and organic solvent action during the spinning process, making it difficult to meet the long-term antibacterial and induction requirements of the complex microenvironment of periodontitis.

[0004] Therefore, there is an urgent need to develop a fibrous membrane for guiding periodontal tissue regeneration and its preparation method to solve the problems in the existing technology. Summary of the Invention

[0005] The purpose of this invention is to provide a fibrous membrane for guiding periodontal tissue regeneration and its preparation method. It can construct a double-layer structure of polylactic acid dense layer and loose layer through electrospinning and electrospraying technology, and respectively composite sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs and bone regeneration-promoting drugs in the corresponding layers. The structure is simple and easy to use, thereby solving the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A fibrous membrane for guiding periodontal tissue regeneration and its preparation method are disclosed, comprising a bilayer structure of a dense polylactic acid (PLA) layer and a loose PLA layer; the dense PLA layer is composited with sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs for barrier epithelial cell ingrowth and release of the anti-inflammatory and antibacterial drugs; the loose PLA layer is composited with sodium hyaluronate microparticles loaded with bone-regenerating drugs for promoting osteoblast adhesion and releasing the bone-regenerating drugs; the fibrous membrane is constructed by a combination of electrospinning and electrospraying techniques. The sodium hyaluronate microparticles form a partially embedded physical anchoring structure on the surface of polylactic acid fibers. The dense layer of sodium hyaluronate microparticles is embedded at the intersection of the fiber network to form a sealing anchor, while the loose layer of sodium hyaluronate microparticles is partially embedded on the surface of a single fiber to form an exposed anchor. The embedding depth of the microparticles is 1 / 3 to 1 / 2 of the microparticle diameter.

[0007] By adopting the above technical solution, a double-layer fiber membrane with zoning function was constructed, which achieved a dual precise time-controlled treatment effect of simultaneously performing antibacterial isolation to block epithelial ingrowth and guiding osteogenic formation to promote bone regeneration in the periodontal defect area.

[0008] As a further aspect of the present invention: the fiber diameter of the polylactic acid dense layer is less than 1 μm and the average pore size is less than 20 μm; the fiber diameter of the polylactic acid loose layer is greater than 2 μm and the average pore size is greater than 30 μm.

[0009] By adopting the above technical solution and limiting the fiber diameter and pore size parameters of the double-layer structure, the physical barrier to epithelial cells and the precise spatial structural regulation of selective entry and proliferation of osteoblasts are achieved.

[0010] As a further aspect of the present invention: the anti-inflammatory and antibacterial drug includes any one of dexamethasone and antibiotics; the bone regeneration promoting drug includes any one of hydroxyapatite, growth factor, BMP-2 recombinant protein, and parathyroid hormone.

[0011] By adopting the above technical solution and introducing specific anti-inflammatory, antibacterial, and bone regeneration-promoting drugs, targeted antibacterial and anti-inflammatory intervention on the periodontal microenvironment and specific biochemical induction of alveolar bone regeneration were achieved.

[0012] As a further aspect of the present invention, the particle size of the sodium hyaluronate microparticles is 500nm-5μm.

[0013] By adopting the above technical solution and limiting the particle size range of drug-loaded microparticles, a stable loading of drugs in the fiber membrane and a spatiotemporally controllable sustained release effect are achieved.

[0014] This invention also discloses a method for preparing a fibrous membrane for guiding periodontal tissue regeneration, characterized by the synergistic application of electrospinning and electrospraying technologies, comprising the following steps: S1: Polylactic acid is dissolved in hexafluoroisopropanol to prepare a low-concentration electrospinning solution. Anti-inflammatory and antibacterial drugs and sodium hyaluronate are dissolved in water to prepare the first microsphere preparation solution. A composite structure of polylactic acid dense layer and sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs is prepared by electrospinning and electrospraying technologies. S2: Polylactic acid is dissolved in hexafluoroisopropanol to prepare a high-concentration electrospinning solution. Bone regeneration drugs and sodium hyaluronate are dissolved in water to prepare a second microsphere preparation solution. A composite structure of polylactic acid loose layer and sodium hyaluronate microparticles loaded with bone regeneration drugs is prepared on the polylactic acid dense layer by electrospinning and electrospraying technology. S3: The collected fiber membrane is vacuum dried to remove hexafluoroisopropanol, and then sterilized by irradiation to obtain the fiber membrane that guides periodontal tissue regeneration. In S1 and S2, the angle between the electrospinning nozzle and the electrospray nozzle is controlled to be 60°-90°, and the ratio of the electrospinning injection speed to the electrospray injection speed is 1:1.2-1.5, so that the microspheres are deposited and partially swollen and embedded in the stage when the fiber solvent has not completely evaporated.

[0015] By adopting the above technical solution and through the synergistic steps of spinning and spraying technology, the integrated molding and preparation of bilayer heterogeneous structures and partitioned drug-loaded microspheres was achieved.

[0016] As a further embodiment of the present invention: in S1, the concentration of the low-concentration electrospinning solution is 3%-10%, the concentration of sodium hyaluronate in the first microsphere preparation solution is 0.5%-2%, the injection speed is 0.5-2.5 ml / h, and the voltage is 8-30 kV.

[0017] By adopting the above technical solution and limiting the preparation parameters of the dense layer, the precise control of the fiber morphology of the dense layer and the efficient composite deposition of hydrophilic antibacterial drug particles were achieved.

[0018] As a further embodiment of the present invention: in S2, the concentration of the high-concentration electrospinning solution is 18%-30%, the concentration of sodium hyaluronate in the second microsphere preparation solution is 0.5%-2%, the injection rate is 0.5-2.5 ml / h, and the voltage is 8-30 kV.

[0019] By adopting the above technical solution and limiting the preparation parameters of the porous layer, stable molding of large-pore fiber network and uniform loading of bone regeneration drug microparticles were achieved.

[0020] As a further aspect of the present invention: in S1, the concentration of the low-concentration electrospinning solution is 5%, the concentration of sodium hyaluronate in the first microsphere preparation solution is 1.5%, the electrospinning injection speed is 1 ml / h, the electrospray injection speed is 1.5 ml / h, the voltage is 20 kV, and the air pressure is 0.05 MPa.

[0021] By adopting the above technical solution and optimizing the specific process parameters of the dense layer, the reproducible preparation of the optimal physical barrier structure of the dense layer and the high encapsulation loading of anti-inflammatory drugs were achieved.

[0022] As a further aspect of the present invention: in S2, the concentration of the high-concentration electrospinning solution is 18%, the concentration of sodium hyaluronate in the second microsphere preparation solution is 1%, the electrospinning injection speed is 1 ml / h, the electrospray injection speed is 1.0 ml / h, the voltage is 20 kV, and the air pressure is 0.05 MPa.

[0023] By adopting the above technical solution and optimizing the specific process parameters of the porous layer, the reproducible preparation of an ideal porous scaffold for the porous layer and the effective protection of the activity of bone-promoting drugs were achieved.

[0024] As a further aspect of the present invention: in step S3, the vacuum drying time is 24-48 hours, and the irradiation sterilization is performed by gamma irradiation with an irradiation dose of 25 kGy.

[0025] By adopting the above technical solutions and standardizing the post-processing procedures, the complete elimination of residual solvents in the fiber membrane and the absolute sterility of the product are achieved, ensuring the safety of clinical applications.

[0026] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention achieves a dual therapeutic effect of antibacterial isolation and osteogenic guidance through a double-layered partitioned fibrous membrane combining a dense layer and a loose layer, which synergistically blocks epithelial cells from the body and promotes bone regeneration through biochemical signals.

[0027] 2. This invention solves the problems of low loading rate and easy deactivation of hydrophilic drugs in organic solvent spinning by combining electrospinning and electrospraying technologies, and realizes efficient loading and spatiotemporally controllable release of water-soluble drugs.

[0028] Other features and advantages of the present invention will be disclosed in detail in the following detailed description and accompanying drawings. Attached Figure Description

[0029] Figure 1 This is a schematic flowchart of a method for preparing a fibrous membrane to guide periodontal tissue regeneration according to an embodiment of the present invention; Figure 2 This is a schematic diagram of the overall structure of a fibrous membrane that guides periodontal tissue regeneration in an embodiment of the present invention. Detailed Implementation

[0030] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all 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.

[0031] This invention utilizes the synergistic application of electrospinning and electrospraying technologies to perform zoned functional optimization of 3D scaffolds used for periodontal regeneration. It achieves precise time-space control by constructing a dense drug-releasing layer on the gingival contact surface of the scaffold to inhibit soft tissue ingrowth, while simultaneously constructing a loose bioactive layer on the bone contact surface to promote bone regeneration. This achieves the dual therapeutic goals of "antibacterial isolation" and "osteogenic guidance" within the same scaffold.

[0032] Example 1 In this embodiment of the invention, a fibrous membrane for guiding periodontal tissue regeneration and its preparation method are described below. Figure 1 , 2 As shown, it includes the following: Polylactic acid (PLGA) bilayer fiber membranes loaded with drug-loaded sodium hyaluronate microparticles were prepared by electrospinning and electrospraying in synergy.

[0033] One layer is a dense PLGA layer with an average pore size of less than 10μm, which can act as a barrier against epithelial cells. The microspheres are loaded with drugs (dexamethasone, antibiotics and other anti-inflammatory and antibacterial drugs) for anti-inflammatory and antibacterial effects. One layer is a loose PLGA layer with large pores. The microspheres are loaded with hydroxyapatite or other bone regeneration-promoting drugs (such as growth factors, BMP-2 recombinant protein, parathyroid hormone, etc.), which can promote osteoblast adhesion.

[0034] Specifically, the preparation method includes the following steps: 1) Dissolve PLGA in hexafluoroisopropanol to prepare a low-concentration electrospinning solution of 3-10%, then dissolve anti-inflammatory and antibacterial drugs and sodium hyaluronate in water to obtain a microsphere preparation solution (sodium hyaluronate concentration of 0.5-2%). Inject the solution at a rate of 0.5-2.5 ml / h and prepare a dense layer at a voltage of 8-30 kV using electrospinning and electrospraying techniques.

[0035] 2) Dissolve PLGA in hexafluoroisopropanol to prepare a high-concentration electrospinning solution of 18-30%. Then dissolve bone regeneration drugs and sodium hyaluronate in water to obtain a microsphere preparation solution (sodium hyaluronate concentration of 0.5-2%). Inject at a rate of 0.5-2.5 ml / h and prepare a porous layer at a voltage of 8-30 kV using electrospinning and electrostatic spraying techniques.

[0036] 3) The collected fiber membranes were vacuum dried to remove hexafluoroisopropanol, followed by irradiation sterilization to obtain the required 3D scaffold. Specifically, electrospinning and electrospraying technologies are used in synergistic fabrication of 3D scaffolds. Electrospinning excels at creating fiber networks that serve as the "skeleton" for cell growth, while electrospraying is adept at preparing micro / nanoparticles loaded with bioactive substances. The combination of the two technologies enables the scaffold to possess an ideal three-dimensional structure while also achieving spatiotemporally controlled release of bioactive molecules (such as growth factors and drugs).

[0037]

[0038] 2. Electrospun fiber membranes were prepared using PLGA as raw material, and sodium hyaluronate microspheres were prepared using sodium hyaluronate as raw material. 3. Prepare a 5% PLGA solution and adjust the injection rate to 1 ml / h. Prepare a 1.5% sodium hyaluronate solution and adjust the injection rate to 1.5 ml / h. Set the voltage to 20 kV and the gas pressure to 0.05 MPa to prepare a dense layered fiber membrane composite microsphere structure. The diameter of the dense layered fiber is less than 1 μm and the average pore size is less than 20 μm.

[0039] 4. Prepare an 18% PLGA solution and adjust the injection rate to 1 ml / h. Prepare a 1% sodium hyaluronate solution and adjust the injection rate to 1.0 ml / h. Set the voltage to 20 kV and the gas pressure to 0.05 MPa to prepare a porous fiber membrane composite microsphere structure. The porous fiber diameter is greater than 2 μm and the average pore size is greater than 30 μm.

[0040] 5. Sodium hyaluronate microparticles can be loaded with a variety of anti-inflammatory, antibacterial, or bone regeneration-promoting drugs, including but not limited to dexamethasone, antibiotics, growth factors, BMP-2 recombinant protein, parathyroid hormone, etc., which are used clinically.

[0041] Specifically, the physical mechanism of the synergistic construction of microsphere-fiber composite structures by electrospinning and electrospraying in this invention includes the following: The main framework of the fiber membrane is constructed by electrospinning technology, while the drug-loaded microparticles are prepared simultaneously by electrospraying technology. In a high-voltage electrostatic field, the polylactic acid (PLGA) spinning solution is stretched by the electric field force to form Taylor cones and spray out continuous micro- and nano-sized fibers. At the same time, the sodium hyaluronate microsphere preparation solution is sprayed under the same electric field. Due to the surface tension and charge repulsion of the aqueous solution, the droplets overcome the surface tension and atomize during flight, breaking into tiny droplets. The water evaporates rapidly before reaching the receiver, solidifies to form sodium hyaluronate microparticles, and randomly deposits in the forming fiber network.

[0042] The particle size of the microspheres is controlled by the injection rate, voltage, and solution concentration, and its theoretical particle size D can be approximately derived using fluid dynamics and electrostatics.

[0043] Where K is a constant, The surface tension of the microsphere preparation solution is denoted by , and Q is the injection velocity. Let Q be the vacuum permittivity, and V be the applied voltage. This invention controls Q by... And V is This ensures that the particle size of the final solidified microparticles falls precisely within the range of... Within this range, the particle size avoids excessively large particles from falling off while ensuring sufficient drug loading volume.

[0044] 2. The regulatory mechanism of cell behavior by the difference in pore size of bilayer structures The pore size difference between the dense and porous layers is achieved by adjusting the PLGA solution concentration. There is an exponential positive correlation between the fiber diameter d and the solution concentration C.

[0045] in, and It is a constant related to the solvent evaporation rate and voltage.

[0046] Dense layer: using a 3%-10% low-concentration solution, fiber diameter The fibers are tightly packed, with an average pore size .

[0047] Because the gingival epithelial cells are large and migrate in sheets, The pore size forms a physical barrier, preventing epithelial cells from penetrating; at the same time, it is loaded with drugs such as dexamethasone to inhibit epithelial proliferation.

[0048] Loose layer: using a 18%-30% high-concentration solution, fiber diameter The interlocking of fibers forms a large-pore network with an average pore size. .

[0049] This pore size range not only allows osteoblasts to grow in freely, but also allows osteoblasts with a diameter typically within [missing information]. It also provides space for the formation of microvascular networks, enabling bone guidance in conjunction with bone regeneration-promoting drugs.

[0050] 3. High loading rate and sustained-release kinetic mechanism of hydrophilic drugs Traditional single electrospinning directly mixes hydrophilic drugs into hydrophobic organic solvents, leading to drug precipitation or inactivation. This invention utilizes water-soluble sodium hyaluronate to encapsulate hydrophilic drugs, completely isolating them from the influence of organic solvents.

[0051] Drug release is controlled by both microsphere degradation and fiber layer diffusion, conforming to the improved Higuchi sustained-release kinetic model, and the cumulative drug release rate is [not specified]. Expressed as:

[0052] in, Let be the amount of drug released at time t. This is the total amount of drug. Higuchi constant based on Fick diffusion, is the polymer degradation rate constant.

[0053] Sodium hyaluronate microparticles gradually swell and degrade in body fluids, providing... The product contains PLGA fiber skeleton that slowly hydrolyzes, and the two work synergistically to achieve a long-lasting sustained release of 14-21 days, matching the periodontal tissue regeneration cycle.

[0054] Drug encapsulation rate The calculation formula is:

[0055] in The actual mass of the drug encapsulated in the microparticles. To ensure the quality of initial drug administration, this method can achieve an encapsulation rate of over 85%.

[0056] Example 2 The technical feature that distinguishes this embodiment from Embodiment 1 is that it includes the preparation of a bilayer drug-loaded fiber membrane under preferred parameters: Dense layer preparation: PLGA was dissolved in hexafluoroisopropanol to prepare an electrospinning solution with a concentration of 5%; dexamethasone and sodium hyaluronate were dissolved in water with a sodium hyaluronate concentration of 1.5% and a drug-to-sodium hyaluronate mass ratio of 1:10 to obtain the first microsphere preparation solution. A dual-nozzle device was used, with an electrospinning injection speed of 1 ml / h, an electrospray injection speed of 1.5 ml / h, a voltage of 20 kV, an air pressure of 0.05 MPa, and a receiving distance of 15 cm. The mixture was deposited on a roller receiver for 2 hours to form a dense layer.

[0057] The diameter of the dense layer fibers was measured to be The average aperture is .

[0058] Preparation of the loose layer: PLGA was dissolved in hexafluoroisopropanol to prepare an 18% electrospinning solution; BMP-2 recombinant protein and sodium hyaluronate were dissolved in water at a concentration of 1% (mass ratio 1:10) to obtain the second microsphere preparation solution, which was then deposited on top of the dense layer. The electrospinning injection rate was 1 ml / h, the electrospray injection rate was 1.0 ml / h, the voltage was 20 kV, and the pressure was 0.05 MPa. Deposition lasted for 3 hours to form the loose layer. The fiber diameter of the loose layer was measured to be... The average aperture is .

[0059] Post-processing: The fiber membrane was placed in a vacuum drying oven and dried under vacuum at room temperature for 24 hours, followed by sterilization by gamma irradiation at a dose of 25 kGy to obtain the finished product. Testing showed that the dexamethasone encapsulation efficiency was 92%, and the BMP-2 activity retention rate was 95%.

[0060] Example 3 The technical feature that distinguishes this embodiment from Embodiment 1 is that it includes the preparation of a bilayer drug-loaded fiber membrane under boundary parameters.

[0061] Dense layer preparation: Prepare an electrospinning solution with a PLGA concentration of 3%; prepare a first microsphere preparation solution with a sodium hyaluronate concentration of 0.5%, i.e., loaded with antibiotics.

[0062] The injection rate was set at 0.5 ml / h, the voltage at 8 kV, and the diameter of the resulting dense layer fibers was [missing information]. The average aperture is .

[0063] Preparation of the loose layer: Prepare an electrospinning solution with a PLGA concentration of 30%; prepare a second microsphere preparation solution with a sodium hyaluronate concentration of 2%, i.e., loaded with parathyroid hormone.

[0064] The injection rate was set at 2.5 ml / h, the voltage at 30 kV, and the diameter of the resulting loose-layer fibers was [missing information]. The average aperture is .

[0065] Post-treatment: Vacuum drying for 48 hours, followed by sterilization by 25kGy gamma irradiation.

[0066] Comparative Example The technical features that distinguish this comparative example from Example 1 are as follows: The preparation of drug-loaded fiber membranes using a single electrospinning technique lacks the synergistic effect of electrostatic spraying.

[0067] Without using electrostatic spraying technology, dexamethasone and BMP-2 were directly dissolved and mixed into 5% and 18% PLGA hexafluoroisopropanol solutions for electrospinning.

[0068] Because the drug has extremely poor solubility in organic solvents, severe needle blockage and drug precipitation occur during the spinning process.

[0069] After forced collection of membrane materials, the encapsulation rate of dexamethasone was only 31%, and the activity retention rate of BMP-2 was only 15% due to protein denaturation caused by direct exposure to organic solvents and high voltage electric fields. Moreover, the drug was released up to 80% in the first 2 days, making sustained release impossible.

[0070] This demonstrates the indispensability of electrostatic spraying synergistic technology in improving the loading rate and protective activity of hydrophilic drugs.

[0071] Example 4 The difference between this embodiment and Embodiment 1 is that this embodiment focuses on verifying and preparing a fiber membrane with particle physical anchoring and a specific spatial distribution structure.

[0072] Specifically, the angle between the electrospinning nozzle and the electrospray nozzle was controlled to be 75°. During the preparation of both the dense and loose layers, the ratio of the electrospinning injection speed to the electrospray injection speed was controlled to be 1:1.4 (i.e., 1 ml / h for spinning and 1.4 ml / h for spraying in Example 1). This ensured that when the microsphere preparation liquid reached the receiver, the hexafluoroisopropanol solvent on the surface of the polylactic acid fiber had not completely evaporated. The microparticles were deposited in this semi-solid state and underwent interfacial swelling. Subsequently, they solidified together with the solvent evaporation, forming a partially embedded physical anchoring structure.

[0073] Scanning electron microscopy revealed that the sodium hyaluronate particles (approximately 1 μm in diameter) in the dense layer were embedded at the intersections of the fiber network, forming a sealing and anchoring effect on the pores, with an embedding depth of approximately 0.4 μm. In contrast, the sodium hyaluronate particles (approximately 3 μm in diameter) in the loose layer were partially embedded on the surface of individual fibers, forming an exposed anchoring effect, with an embedding depth of approximately 1.2 μm. The embedding depths in both cases were 1 / 3 to 1 / 2 of the particle diameter.

[0074] This invention provides a fiber membrane for guiding periodontal tissue regeneration and its preparation method. It can construct a double-layer structure of polylactic acid dense layer and loose layer through electrospinning and electrospraying technology, and respectively composite sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs and bone regeneration promoting drugs in the corresponding layers.

[0075] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0076] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A fibrous membrane for guiding periodontal tissue regeneration, characterized in that, The structure comprises a double-layer structure consisting of a dense polylactic acid (PLA) layer and a loose PLA layer. The dense PLA layer is composited with sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs, which facilitate the ingrowth of barrier epithelial cells and the release of these drugs. The loose PLA layer is composited with sodium hyaluronate microparticles loaded with bone-regenerating drugs, which promote osteoblast adhesion and the release of these drugs. The fiber membrane is constructed through a combination of electrospinning and electrospraying techniques. The sodium hyaluronate microparticles form a partially embedded physical anchoring structure on the surface of polylactic acid fibers. The dense layer of sodium hyaluronate microparticles is embedded at the intersection of the fiber network to form a sealing anchor, while the loose layer of sodium hyaluronate microparticles is partially embedded on the surface of a single fiber to form an exposed anchor. The embedding depth of the microparticles is 1 / 3 to 1 / 2 of the microparticle diameter.

2. The fibrous membrane for guiding periodontal tissue regeneration according to claim 1, characterized in that, The dense polylactic acid layer has a fiber diameter of less than 1 μm and an average pore size of less than 20 μm; the loose polylactic acid layer has a fiber diameter of greater than 2 μm and an average pore size of greater than 30 μm.

3. The fibrous membrane for guiding periodontal tissue regeneration according to claim 1, characterized in that, The anti-inflammatory and antibacterial drugs include any one of dexamethasone and antibiotics; the bone regeneration-promoting drugs include any one of hydroxyapatite, growth factors, BMP-2 recombinant protein, and parathyroid hormone.

4. The fibrous membrane for guiding periodontal tissue regeneration according to claim 1, characterized in that, The particle size of the sodium hyaluronate microparticles is 500nm-5μm.

5. A method for preparing a fibrous membrane for guiding periodontal tissue regeneration, used to prepare the fibrous membrane according to any one of claims 1 to 4, characterized in that, The combined use of electrospinning and electrospraying technologies includes the following steps: S1: Polylactic acid is dissolved in hexafluoroisopropanol to prepare a low-concentration electrospinning solution. Anti-inflammatory and antibacterial drugs and sodium hyaluronate are dissolved in water to prepare the first microsphere preparation solution. A composite structure of polylactic acid dense layer and sodium hyaluronate microparticles loaded with anti-inflammatory and antibacterial drugs is prepared by electrospinning and electrospraying technologies. S2: Polylactic acid is dissolved in hexafluoroisopropanol to prepare a high-concentration electrospinning solution. Bone regeneration drugs and sodium hyaluronate are dissolved in water to prepare a second microsphere preparation solution. A composite structure of polylactic acid loose layer and sodium hyaluronate microparticles loaded with bone regeneration drugs is prepared on the polylactic acid dense layer by electrospinning and electrospraying technology. S3: The collected fiber membrane is vacuum dried to remove hexafluoroisopropanol, and then sterilized by irradiation to obtain the fiber membrane that guides periodontal tissue regeneration. In S1 and S2, the angle between the electrospinning nozzle and the electrospray nozzle is controlled to be 60°-90°, and the ratio of the electrospinning injection speed to the electrospray injection speed is 1:1.2-1.5, so that the microspheres are deposited and partially swollen and embedded in the stage when the fiber solvent has not completely evaporated.

6. The method for preparing a fibrous membrane for guiding periodontal tissue regeneration according to claim 5, characterized in that, In step S1, the concentration of the low-concentration electrospinning solution is 3%-10%, the concentration of sodium hyaluronate in the first microsphere preparation solution is 0.5%-2%, the injection rate is 0.5-2.5 ml / h, and the voltage is 8-30 kV.

7. The method for preparing a fibrous membrane for guiding periodontal tissue regeneration according to claim 5, characterized in that, In step S2, the concentration of the high-concentration electrospinning solution is 18%-30%, the concentration of sodium hyaluronate in the second microsphere preparation solution is 0.5%-2%, the injection rate is 0.5-2.5 ml / h, and the voltage is 8-30 kV.

8. The method for preparing a fibrous membrane for guiding periodontal tissue regeneration according to claim 6, characterized in that, In step S1, the concentration of the low-concentration electrospinning solution is 5%, the concentration of sodium hyaluronate in the first microsphere preparation solution is 1.5%, the electrospinning injection speed is 1 ml / h, the electrospray injection speed is 1.5 ml / h, the voltage is 20 kV, and the air pressure is 0.05 MPa.

9. The method for preparing a fibrous membrane for guiding periodontal tissue regeneration according to claim 7, characterized in that, In step S2, the concentration of the high-concentration electrospinning solution is 18%, the concentration of sodium hyaluronate in the second microsphere preparation solution is 1%, the electrospinning injection speed is 1 ml / h, the electrospray injection speed is 1.0 ml / h, the voltage is 20 kV, and the air pressure is 0.05 MPa. A method for preparing a fibrous membrane for guiding periodontal tissue regeneration according to claim 5, characterized in that, In step S3, the vacuum drying time is 24-48 hours, and the irradiation sterilization is performed using gamma irradiation with an irradiation dose of 25 kGy.

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