Guided tissue regeneration membrane as well as preparation method and application thereof

Abstract

The invention provides a guided tissue regeneration membrane as well as a preparation method and application thereof. The guided tissue regeneration membrane is formed by interweaving and stacking cellosilk and has a porous structure; wherein the guided tissue regeneration membrane is derived from a fiber raw material, and the fiber raw material comprises a synthetic high polymer material and a natural high polymer material; the synthetic high polymer material comprises a non-elastomer material and an elastomer material; the non-elastomer material is a polyester compound. The guided tissue regeneration membrane disclosed by the invention does not swell under the condition that some tissue liquid or other liquid is more and exists for a long time (such as oral saliva); the material has a porous structure, is appropriate in pore size, can prevent fibroblasts, epithelial cells and other peripheral tissues with high migration speed from entering a bone defect area, and has a good physical barrier effect.

Description

Technical Field

[0001] The invention relates to a guided tissue regeneration membrane and a preparation method and application thereof, belonging to the field of medical implant materials. Background Art

[0002] Guided tissue regeneration (GTR) is a method of regenerating periodontal tissue proposed by Dahlin et al. in the 1980s and 1990s. It is based on the theory that "the type of cells that first proliferate in the tissue defect determines the type of wound healing." A membrane material is placed between the periodontal connective tissue and the tooth root as a barrier to prevent soft tissue cells (epithelial cells, fibroblasts, etc.) with too fast proliferation and migration rates from entering the underlying periodontal defect area, thereby selectively creating space for the periodontal ligament cells and osteoblasts with slower migration rates below to reattach to the root surface for bone reconstruction activities, thereby achieving true periodontal tissue regeneration.

[0003] An ideal barrier membrane should possess the following characteristics: shielding properties, biocompatibility, tissue integration, dimensional stability, operability, selective permeability, and spatial maintenance. Existing guided tissue regeneration membrane materials typically incorporate natural hydrophilic materials such as collagen, gelatin, and polysaccharides with synthetic materials such as polylactic acid to form a composite membrane. This promotes the adhesion and growth of tissue cells to the membrane material, improving the biocompatibility and tissue repair performance of the guided tissue regeneration membrane.

[0004] For example, CN104922732A discloses a method for preparing oral biofilms, in which collagen and chondroitin sulfate are mixed into a slurry, which is then freeze-dried and pressed into a collagen composite film. However, when the oral biofilm contains a large amount of tissue fluid or other liquids for a long time (such as oral saliva), the hydrophilic materials such as collagen, gelatin, and polysaccharides in the repair membrane will swell, resulting in structural changes such as fiber slippage or membrane deformation. Such changes usually lead to poor adhesion of the membrane to the implant site, displacement after implantation, or loss of the original pore barrier function, resulting in exposure and infection problems. Bone screws are usually required for fixation, which is cumbersome to operate, and bone screws are usually non-absorbable, affecting the appearance.

[0005] To address the problem of membrane slippage or deformation caused by swelling of hydrophilic materials such as collagen, a crosslinking agent can be added to reduce swelling caused by dissolution. For example, CN109513046A discloses an absorbable oral repair membrane and its preparation method. The oral repair membrane uses gelatin and polycaprolactone as raw materials. Electrospinning is used to produce a nanofiber membrane, which is then laminated in the order of gelatin layer, polycaprolactone layer, and gelatin layer to produce a three-layer oral repair membrane with a gradually varying fiber diameter. Glutaraldehyde is added as a crosslinker during the preparation of the gelatin fiber membrane, but glutaraldehyde has certain toxicity.

[0006] In addition, adding elastomeric polymer materials to the electrospinning solution can reduce the pore size of the electrospun fiber membrane and play a better shielding role. However, the fiber membrane prepared by mixed electrospinning shrinks during the post-processing process, resulting in a smaller area of ​​the entire membrane material after drying, thereby increasing the production cost. Moreover, the pore size of the fiber membrane is too small after shrinkage, which is not conducive to the exchange of nutrients.

[0007] Therefore, developing a solution that can solve both the swelling problem and the problem of shrinkage of the fiber membrane resulting in a smaller area of ​​the entire membrane material after drying has become a research challenge at this stage. Summary of the Invention

[0008] Problems to be solved by the invention

[0009] In response to the technical problems existing in the prior art, the present invention first provides a guided tissue regeneration membrane that overcomes the swelling phenomenon that occurs in guided tissue regeneration membranes based on hydrophilic materials, resulting in thickening of the guided tissue regeneration membrane, poor adhesion, and susceptibility to slip deformation, which in turn poses a risk of membrane material leakage. It also solves the problem that fiber membranes containing elastomeric polymer materials prepared by electrospinning shrink during post-processing, resulting in a reduced pore size of the fiber membrane, which is not conducive to the exchange of nutrients, and the problem that the reduced fiber membrane size leads to increased production costs. The guided tissue regeneration membrane of the present invention has good softness, adhesion, and elasticity, effectively promotes soft tissue healing, and reduces the rate of exposure infection.

[0010] Furthermore, the present invention also provides a method for preparing a guided tissue regeneration membrane. The preparation method is simple and easy, the raw materials are easy to obtain, and it is suitable for mass production.

[0011] Solutions for solving problems

[0012] The present invention provides a guided tissue regeneration membrane, wherein the guided tissue regeneration membrane is formed by interweaving and stacking fiber filaments and has a porous structure; wherein,

[0013] The guided tissue regeneration membrane is derived from fiber raw materials, and the fiber raw materials include synthetic polymer materials and natural polymer materials;

[0014] The synthetic polymer material includes non-elastomeric materials and elastomeric materials;

[0015] The non-elastomeric material is a polyester compound.

[0016] Furthermore, the mass ratio of the non-elastomeric material, the natural polymer material and the elastomeric material is (0.5-2):(1-6):(1-6), preferably (0.5-1.5):(1-4.5):(1-4.5).

[0017] Furthermore, the polyester compound includes one or a combination of two or more of polylactic acid, polycaprolactone, polyglycolic acid, and glycolic acid-lactic acid copolymer; and / or,

[0018] The natural polymer material includes one or a combination of two or more of gelatin, collagen, silk fibroin, hyaluronic acid, and cellulose.

[0019] Furthermore, the elastomeric material includes one or a combination of two or more of polytrimethylene carbonate, styrene-butadiene-styrene block copolymer, styrene-isoprene-styrene block copolymer, styrene-ethylene-butylene-styrene block copolymer, and styrene-ethylene-propylene-styrene type block copolymer; preferably, the elastomeric material is polytrimethylene carbonate; further preferably, the weight average molecular weight of the polytrimethylene carbonate is greater than 150,000 Da.

[0020] Furthermore, the fiber raw material is also doped with osteogenic induction powder.

[0021] Furthermore, the average pore size of the guided tissue regeneration membrane is 0.1-5 μm; the tensile strength of the guided tissue regeneration membrane is 2.5-3.5 MPa; and the maximum suturing force of the guided tissue regeneration membrane is 2.4-3.2N.

[0022] The present invention also provides a method for preparing the guided tissue regeneration membrane according to the present invention, which comprises the following steps:

[0023] Dissolving fiber raw materials in an organic solvent to obtain a spinning solution;

[0024] A film-like product is prepared by a spinning process;

[0025] a step of post-processing the membrane product to obtain a guided tissue regeneration membrane;

[0026] Preferably, the spinning process may include one or a combination of two or more of electrospinning technology, centrifugal spinning technology, hot melt spinning technology, and melt electrospinning technology.

[0027] Furthermore, the mass concentration of the fiber raw material in the spinning solution is 5%-10%; and / or the organic solvent includes one or a combination of two or more of hexafluoroisopropanol, trifluoroethanol, chloroform, dichloromethane, tetrahydrofuran, and N,N'-dimethylformamide; and / or the parameters of the electrospinning technology include: adjusting the voltage of the high-voltage generator to 15-33 kV, adjusting the rate of the microinjection pump to 2-10 mL / h, adjusting the receiving distance of the receiving device to 18-24 cm, and adjusting the speed of the receiving roller to 50-500 rpm; controlling the temperature during the electrospinning process to 20-26°C and the humidity to 60-70%.

[0028] Furthermore, the post-treatment includes the steps of removing residual organic solvent and / or drying; preferably, the film-like product is soaked in an alcohol solvent to remove residual organic solvent; more preferably, the soaking is performed 1-10 times.

[0029] The present invention also provides a use of the guided tissue regeneration membrane according to the present invention for preparing an oral repair membrane.

[0030] Effects of the Invention

[0031] The guided tissue regeneration membrane of the present invention will not swell when some tissue fluid or other fluid is present in large amounts for a long time (such as oral saliva).

[0032] Furthermore, the guided tissue regeneration membrane has a porous structure with an appropriate pore size, which can block surrounding tissues such as fibroblasts and epithelial cells with faster migration speeds from entering the bone defect area, and has a good physical barrier effect.

[0033] Furthermore, the guided tissue regeneration membrane of the present invention is soft in texture, has good adhesion and elasticity, is simple to operate clinically, does not require the use of bone screws for fixation, does not slip during use, and reduces the exposure infection rate.

[0034] The preparation method of the guided tissue regeneration membrane of the present invention is simple and easy, the raw materials are easy to obtain, and it is suitable for mass production. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 A scanning electron micrograph (magnification ×200) of the guided tissue regeneration membrane of Example 1 is shown.

[0036] Figure 2 The scanning electron microscope image (magnification ×200) of the film-like product of step (2) in Comparative Example 1 is shown.

[0037] Figure 3 The scanning electron microscope image (magnification ×200) of the guided tissue regeneration membrane in step (3) of Comparative Example 1 is shown.

[0038] Figure 4 A scanning electron micrograph (magnification ×500) of the guided tissue regeneration membrane of Example 2 is shown.

[0039] Figure 5 The adhesion effect of the guided tissue regeneration membrane of Example 1 on the alveolar bone is shown.

[0040] Figure 6 The graph shows the adhesion effect of the guided tissue regeneration membrane of Comparative Example 3 on the alveolar bone.

[0041] Figure 7 The photographs of the surgical process after the guided tissue regeneration membrane of Example 1 and the GUIDOR control group were used in an animal model of tooth extraction sockets are shown, wherein the left picture is Example 1 and the right picture is the GUIDOR control group.

[0042] Figure 8 The figure shows the wound healing condition on the second day after surgery, wherein the left figure is Example 1 and the right figure is the GUIDOR control group.

[0043] Figure 9 The figure shows the wound healing status on the 6th day after surgery, wherein the left figure is Example 1 and the right figure is the GUIDOR control group.

[0044] Figure 10 The figure shows the wound healing status on the 7th day after surgery, wherein the left figure is Example 1 and the right figure is the GUIDOR control group.

[0045] Figure 11 The figure shows the wound healing status on the 30th day after surgery, wherein the left figure is Example 1 and the right figure is the GUIDOR control group.

[0046] Figure 12 The results show the bone repair after the guided tissue regeneration membrane of Example 1 was used in an animal model of tooth extraction sockets and after dissection 30 days after surgery.

[0047] Figure 13 The figure shows the bone repair after the GUIDOR control group guided tissue regeneration membrane was used in the tooth extraction socket animal model after dissection 30 days after surgery. DETAILED DESCRIPTION

[0048] Various exemplary embodiments, features, and aspects of the present invention will be described in detail below. The word "exemplary" is used herein to mean "serving as an example, embodiment, or illustration." Any embodiment described herein as "exemplary" is not necessarily to be construed as superior or preferred over other embodiments.

[0049] In addition, numerous specific details are provided in the following detailed description to better illustrate the present invention. Those skilled in the art will appreciate that the present invention can be practiced without certain specific details. In other instances, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main points of the present invention.

[0050] Unless otherwise stated, the units used in this specification are international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0051] In this specification, the use of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process.

[0052] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "embodiments," etc., mean that the specific elements (e.g., features, structures, properties, and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not be present in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0053] In this specification, a numerical range expressed using "a numerical value A - a numerical value B" means a range including the endpoints A and B.

[0054] In this specification, when "normal temperature" or "room temperature" is used, the temperature may be 10-40°C.

[0055] <First Aspect>

[0056] A first aspect of the present invention provides a guided tissue regeneration membrane, wherein the guided tissue regeneration membrane is formed by interweaving and stacking fiber filaments and has a porous structure; wherein,

[0057] The guided tissue regeneration membrane is derived from fiber raw materials, and the fiber raw materials include synthetic polymer materials and natural polymer materials;

[0058] The synthetic polymer material includes non-elastomeric materials and elastomeric materials;

[0059] The non-elastomeric material is a polyester compound.

[0060] The present invention does not specifically limit the method for forming the fiber filaments; the filaments can be prepared using any commonly used spinning process in the art. Specifically, the guided tissue regeneration membrane of the present invention can be prepared by electrospinning, melt spinning, centrifugal spinning, or the like, preferably using electrospinning. In the present invention, the diameter of the fiber filaments can be 0.001-100 μm, preferably 0.1-5 μm.

[0061] The principle of electrospinning is to apply a high voltage to the polymer liquid during the electrospinning process to introduce electric charges into the liquid. When the charge in the liquid accumulates to a certain amount, the liquid will form a Taylor cone at the nozzle. Under the action of the external electric field force, the surface tension is overcome to form a liquid jet. Then, under the combined action of electrostatic repulsion, Coulomb force (Coulomb) and surface tension, the polymer jet moves along an irregular spiral trajectory. The jet is pulled and stretched in a very short time. As the solvent evaporates or heat dissipates, the polymer jet solidifies to form micron / nanofibers. During the electrospinning process, many parameters will affect the final electrospun fibers. By controlling the process parameters, micron / nanofibers of different sizes, morphologies and structures can be prepared.

[0062] During the electrospinning process of the present invention, the process parameters will affect the film-like product obtained by electrospinning. By controlling the process parameters, film-like products of different sizes, shapes, and structures can be prepared. The present invention has no particular requirements for the electrospinning method, and can be an electrospinning method commonly used in the art. Specifically, the present invention dissolves the fiber raw material in a suitable solvent to prepare a spinning solution; then, electrospinning is used to spin the spinning solution into a film-like product composed of interwoven and stacked fiber filaments.

[0063] Furthermore, the guided tissue regeneration membrane of the present invention, composed of interwoven and stacked fibers, possesses a porous structure. The appropriately sized pores prevent rapidly migrating fibroblasts, epithelial cells, and other surrounding tissues from entering the bone defect area, providing a strong physical barrier. Specifically, in the present invention, the average pore size of the guided tissue regeneration membrane is 0.1-5 μm.

[0064] The guided tissue regeneration membrane of the present invention is derived from fiber raw materials, and the fiber raw materials include synthetic polymer materials and natural polymer materials; the synthetic polymer materials include non-elastic materials and elastomeric materials.

[0065] In the present invention, the non-elastomeric material is a polyester compound. The inventors of the present invention have discovered that the polyester compound does not swell in the presence of a large amount of tissue fluid or other fluid for a long time (such as oral saliva). Specifically, the polyester compound can be a hydrophobic material.

[0066] Furthermore, the mass ratio of the non-elastomer material, the natural polymer material, and the elastomeric material is (0.5-2):(1-6):(1-6), preferably (0.5-1.5):(1-4.5):(1-4.5). By controlling the mass ratio of the non-elastomer material, the natural polymer material, and the elastomeric material to (0.5-2):(1-6):(1-6), it is possible to effectively solve the problem of exposure and infection caused by the membrane product becoming thicker and slipping due to excessive swelling of the hydrophilic substance content in the existing guided tissue regeneration membrane, and it is also possible to effectively solve the problem of the membrane product shrinking after post-processing, resulting in changes in pore size and increased production costs.

[0067] Specifically, in the present invention, the polyester compound may include one or a combination of two or more of polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and glycolic acid-lactic acid copolymer (PLGA); the natural polymer material may include one or a combination of two or more of gelatin, collagen, silk fibroin, hyaluronic acid, cellulose, etc. The elastomeric material may include one or a combination of two or more of polytrimethylene carbonate (PTMC), styrene-butadiene-styrene block copolymer (SBS), styrene-isoprene-styrene block copolymer (SIS), styrene-ethylene-butylene-styrene block copolymer (SEBS), and styrene-ethylene-propylene-styrene type block copolymer (SEPS).

[0068] In the present invention, polytrimethylene carbonate (PTMC) has excellent biocompatibility and degradation properties. Its degradation cycle is short in the oral environment, and it degrades to alkalinity, significantly reducing the possibility of inflammation during the degradation process. Furthermore, when the weight-average molecular weight of PTMC is 150,000 Da or greater, it can reduce the swelling of natural polymer materials. Therefore, when PTMC is used as an elastomer material, it is preferably a weight-average molecular weight of 150,000 Da or greater.

[0069] Furthermore, the fiber raw material of the present invention is also doped with osteogenic inductive powder. The osteogenic inductive powder is a powder having osteogenic inductive ability. For example, the osteogenic inductive powder may include one of hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcium oxide, calcium silicate, calcium sulfate, calcium carbonate, strontium carbonate, strontium phosphate, sodium phosphate, magnesium phosphate, magnesium oxide, silicon oxide, zinc phosphate, zinc oxide, bioglass, and metallic magnesium powder, or a mixture of two or more of these. The addition of the osteogenic inductive powder to the present invention can promote new bone regeneration.

[0070] Furthermore, the content of the osteogenic inductive powder is not particularly limited in the present invention and can be added as needed. Specifically, considering the situation of bone regeneration, the mass ratio of the non-elastomeric material to the osteogenic inductive powder can be 1:0.25-5.

[0071] Furthermore, in the present invention, the tensile strength of the guided tissue regeneration membrane is 2.5-3.5 MPa, and the maximum suturing force of the guided tissue regeneration membrane is 2.4-3.2 N. The guided tissue regeneration membrane of the present invention has good softness, adhesion and elasticity, effectively promotes soft tissue healing, and reduces the exposure infection rate.

[0072] <Second Aspect>

[0073] A second aspect of the present invention provides a method for preparing the guided tissue regeneration membrane according to the first aspect of the present invention, characterized in that it comprises the following steps:

[0074] Dissolving fiber raw materials in an organic solvent to obtain a spinning solution;

[0075] A film-like product is prepared by a spinning process;

[0076] a step of post-processing the membrane product to obtain a guided tissue regeneration membrane;

[0077] Preferably, the spinning process may include one or a combination of two or more of electrospinning technology, centrifugal spinning technology, hot melt spinning technology, and melt electrospinning technology.

[0078] In some specific embodiments, the present invention uses a fiber material prepared by an electrospinning method. Specifically, in the electrospinning step, a fiber raw material is prepared in advance, and the fiber raw material is dissolved in a suitable solvent to prepare a spinning solution of a certain concentration of fiber raw material. Preferably, the mass concentration of the fiber raw material in the spinning solution is 5%-10%. Among them, the fiber raw material can be the synthetic polymer material, natural polymer material and optional osteogenic induction powder of the first aspect. There is no particular limitation on the specific concentration of the type of solvent for forming the solution, as long as it can meet the requirements of the subsequent electrospinning process. For example, a suitable solvent can be one or a combination of two or more of hexafluoroisopropanol, trifluoroethanol, chloroform, dichloromethane, tetrahydrofuran, and N,N'-dimethylformamide.

[0079] During the electrospinning process, desired fiber materials can be produced by adjusting spinning parameters, such as voltage, extrusion flow rate, electric field receiving distance, and spinning environment. Preferably, the electrospinning process parameters described in the present invention include: adjusting the voltage of the high-voltage generator to 15-33 kV, adjusting the rate of the microinjection pump to 2-10 mL / h, adjusting the receiving distance of the receiving device to 18-24 cm, and adjusting the receiving roller speed to 50-500 rpm; and controlling the temperature during the electrospinning process to 20-26°C and the humidity to 60-70%.

[0080] Furthermore, post-treatment includes the steps of removing residual organic solvent and / or drying; preferably, the film-like product is soaked in an alcohol solvent to remove residual organic solvent; more preferably, the soaking is performed 1-10 times.

[0081] The present invention is not particularly limited to alcohol solvents; they may be any commonly used solvent in the art, such as methanol and ethanol. Preferably, the present invention uses ethanol at a concentration of 75% to 95%. Repeated soaking with 75% to 95% ethanol can effectively remove residual solvent.

[0082] The present invention does not impose any particular limitation on drying. Generally, the drying can be carried out in an air atmosphere. The drying temperature can be 30-40° C., and the drying time can be 6-12 hours.

[0083] Finally, the obtained guided tissue regeneration membrane can be cut, sealed and packaged, and then sterilized by irradiation, for example, by Co-60 gamma ray irradiation.

[0084] <Third Aspect>

[0085] The third aspect of the present invention provides a use of the guided tissue regeneration membrane according to the present invention for preparing an oral repair membrane.

[0086] The guided tissue regeneration membrane of the present invention can have the following effects as an oral repair membrane:

[0087] 1. It acts as a physical barrier, preventing fibroblasts and endothelial cells with faster migration speed from entering the bone defect site, and maintaining a relatively stable environment in the bone defect site.

[0088] 2. Protect the integrity of local blood clots, reduce the loss of active substances in the blood clots, and facilitate the vascularization of bone defect areas.

[0089] 3. It can be used as a carrier of osteoinductive factors to better promote bone regeneration.

[0090] 4. It has a suitable porous structure to simulate the extracellular matrix environment in the original organism, providing a three-dimensional growth space for cell attachment, growth, proliferation and differentiation, which is beneficial to the regeneration of bone tissue.

[0091] Example

[0092] The embodiments of the present invention will be described in detail below with reference to the examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present invention and should not be construed as limiting the scope of the invention. Where specific conditions are not specified in the examples, the methods were performed according to conventional conditions or the conditions recommended by the manufacturer. Where the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be obtained commercially.

[0093] Example 1

[0094] (1) PCL (polycaprolactone), gelatin, and PTMC (polytrimethylene carbonate, weight-average molecular weight 150,000 Da) were mixed uniformly in a mass ratio of 1:2:2, and then hexafluoroisopropanol was added and stirred to form a spinning solution with a mass-to-volume ratio of 5 g / 100 mL;

[0095] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 200 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%, and then a membrane product was obtained by electrospinning.

[0096] (3) The membrane product was repeatedly immersed in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the entire process, the membrane product did not shrink and had excellent mechanical properties.

[0097] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0098] Example 2

[0099] (1) PCL (polycaprolactone), collagen, PTMC (polytrimethylene carbonate, weight-average molecular weight 300,000 Da) and hydroxyapatite were mixed in a mass ratio of 0.5:2.3:2:0.2, and then hexafluoroisopropanol was added and stirred to form a spinning solution with a mass-to-volume ratio of 7 g / 100 mL;

[0100] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 2 mL / h, the voltage difference of the high-voltage generator was adjusted to 15 kV, the receiving distance of the receiving device was adjusted to 18 cm, and the speed of the receiving roller was adjusted to 500 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%, and then a membrane product was obtained by electrospinning.

[0101] (3) The membrane product was repeatedly immersed in a 75% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the entire process, the membrane product did not shrink and had excellent mechanical properties.

[0102] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0103] Example 3

[0104] (1) PLA (polylactic acid), gelatin, and PTMC (polytrimethylene carbonate, weight-average molecular weight 150,000 Da) were mixed uniformly in a mass ratio of 1:2:3, and then hexafluoroisopropanol was added and stirred to form a spinning solution with a mass-to-volume ratio of 5 g / 100 mL;

[0105] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 8 mL / h, the voltage difference of the high-voltage generator was adjusted to 30 kV, the receiving distance of the receiving device was adjusted to 20 cm, and the speed of the receiving roller was adjusted to 50 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%, and then a membrane product was obtained by electrospinning.

[0106] (3) The membrane product was repeatedly immersed in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the entire process, the membrane product did not shrink and had excellent mechanical properties.

[0107] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0108] Example 4

[0109] (1) PLA (polylactic acid), hyaluronic acid and styrene-butadiene-styrene block copolymer (SBS) were mixed at a mass ratio of 1.5:1:1, and then a mixed solvent of N,N-dimethylformamide and tetrahydrofuran (the mass ratio of N,N-dimethylformamide to tetrahydrofuran was 50:50) was added and stirred to form a spinning solution with a mass volume ratio of 8 g / 100 mL;

[0110] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 10 mL / h, the voltage difference of the high-voltage generator was adjusted to 33 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 100 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%, and then a membrane product was obtained by electrospinning.

[0111] (3) The membrane product was repeatedly immersed in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the entire process, the membrane product did not shrink and had excellent mechanical properties.

[0112] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0113] Example 5

[0114] (1) PGA (polyglycolic acid), silk fibroin, styrene-ethylene-propylene-styrene block copolymer (SEPS), and calcium carbonate were mixed in a mass ratio of 2:6:4.5:2, and then chloroform was added and stirred to form a spinning solution with a mass volume ratio of 5 g / 100 mL;

[0115] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 300 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0116] (3) The membrane product was repeatedly immersed in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the entire process, the membrane product did not shrink and had excellent mechanical properties.

[0117] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0118] Example 6

[0119] (1) PLGA (poly(lactic-co-glycolic acid), cellulose, and styrene-isoprene-styrene block copolymer (SIS)) were mixed at a mass ratio of 0.5:4.5:6, and then a mixed solvent of N,N-dimethylformamide and tetrahydrofuran (the mass ratio of N,N-dimethylformamide to tetrahydrofuran was 40:60) was added and stirred to prepare a spinning solution with a mass volume ratio of 10 g / 100 mL;

[0120] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 8 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 22 cm, and the speed of the receiving roller was adjusted to 500 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0121] (3) The membrane product is dried in an oven at 37°C to remove the solvent, thereby obtaining a guided tissue regeneration membrane. During the entire process, the membrane product does not shrink and has excellent mechanical properties.

[0122] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0123] Example 7

[0124] (1) PCL (polycaprolactone), gelatin, and PTMC (polytrimethylene carbonate, weight-average molecular weight 140,000 Da) were mixed uniformly in a mass ratio of 1:2:2, and then hexafluoroisopropanol was added and stirred to form a spinning solution with a mass-to-volume ratio of 5 g / 100 mL;

[0125] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 300 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0126] (3) The membrane product was repeatedly soaked in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the post-processing process, the membrane product did not shrink and had excellent mechanical properties.

[0127] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0128] Comparative Example 1

[0129] (1) Gelatin and PTMC (polytrimethylene carbonate, weight-average molecular weight 150,000 Da) were mixed uniformly in a mass ratio of 3:1, and then hexafluoroisopropanol was added and stirred uniformly to prepare a spinning solution with a mass-to-volume ratio of 5 g / 100 mL;

[0130] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 200 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0131] (3) The membrane product was repeatedly soaked in 95% ethanol solution to remove the hexafluoroisopropanol residue, and then dried to obtain a guided tissue regeneration membrane. However, the fiber membrane showed severe shrinkage when soaked in 95% alcohol, with the shrinkage range being 1 / 3-1 / 2.

[0132] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0133] Comparative Example 2

[0134] (1) Gelatin and PTMC (polytrimethylene carbonate, weight-average molecular weight 150,000 Da) were mixed uniformly in a mass ratio of 1:1, and then hexafluoroisopropanol was added and stirred uniformly to prepare a spinning solution with a mass-to-volume ratio of 5 g / 100 mL;

[0135] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 200 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0136] (3) The membrane product was repeatedly soaked in 95% ethanol solution to remove the hexafluoroisopropanol residue, and then dried to obtain a guided tissue regeneration membrane. However, the membrane product showed severe shrinkage when soaked in 95% alcohol, with the shrinkage range being 1 / 3-1 / 2.

[0137] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0138] Comparative Example 3

[0139] (1) PCL (polycaprolactone) and gelatin were mixed in a mass ratio of 1:2, and then hexafluoroisopropanol was added to prepare a mass volume ratio of 5g / 100mL, and stirred to form a spinning solution;

[0140] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 200 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0141] (3) The membrane product was repeatedly soaked in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the post-processing process, the membrane product did not shrink and had excellent mechanical properties.

[0142] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0143] Comparative Example 4

[0144] (1) PCL (polycaprolactone) and gelatin were mixed in a mass ratio of 4:1, and then hexafluoroisopropanol was added to prepare a mass volume ratio of 5g / 100mL, and stirred to form a spinning solution;

[0145] (2) The spinning solution was loaded into a syringe, the rate of the microinjection pump was adjusted to 6 mL / h, the voltage difference of the high-voltage generator was adjusted to 32 kV, the receiving distance of the receiving device was adjusted to 24 cm, and the speed of the receiving roller was adjusted to 200 rpm; the temperature during the electrospinning process was controlled to be approximately 23°C and the humidity to be approximately 65%; and then electrospinning was performed to obtain a membrane product.

[0146] (3) The membrane product was repeatedly soaked in a 95% ethanol solution to remove the residual hexafluoroisopropanol, and then dried to obtain a guided tissue regeneration membrane. During the post-processing process, the membrane product did not shrink and had excellent mechanical properties.

[0147] (4) The guided tissue regeneration membrane is sealed and packaged, and subjected to Co-60 gamma ray irradiation sterilization treatment to obtain a guided tissue regeneration membrane product.

[0148] Performance Testing

[0149] 1. SEM image of guided tissue regeneration membrane

[0150] Figure 1 The following is a scanning electron micrograph of the guided tissue regeneration membrane of Example 1 (magnification ×200). Figure 2 The scanning electron microscope image (magnification × 200) of the film-like product of step (2) in Comparative Example 1 is shown. Figure 3 The scanning electron microscope image (magnification ×200) of the guided tissue regeneration membrane in step (3) of Comparative Example 1 is shown. Figure 4A scanning electron micrograph (magnification ×500) of the guided tissue regeneration membrane of Example 2 is shown.

[0151] SEM results show that the membrane product of step (2) in Comparative Example 1 is relatively loose, while the fibers of the guided tissue regeneration membrane in step (3) in Comparative Example 1 exhibit curling and a denser fiber structure. Furthermore, the fiber membrane obtained after post-treatment of the membrane product in Comparative Example 1 shrinks, resulting in a smaller overall surface area. When a certain amount of PCL is added (Example 1), the fiber structure does not become denser, the fiber membrane does not shrink, and the surface area remains unchanged.

[0152] 2. Swelling performance test

[0153] The guided tissue regeneration membranes of Examples 1-7 and the guided tissue regeneration membranes of Comparative Examples 1-3 were respectively immersed in a PBS solution for 7 days. The thickness of the guided tissue regeneration membranes was measured with a thickness gauge before and after immersion for 7 days. The average value of the three measurements was taken. The results are shown in Table 1 below:

[0154] Table 1

[0155] Sample number Starting thickness (mm) Thickness after 7 days of immersion (mm) Example 1 0.25 0.26 Example 2 0.22 0.24 Example 3 0.20 0.21 Example 4 0.25 0.27 Example 5 0.32 0.33 Example 6 0.30 0.32 Example 7 0.26 0.32 Comparative Example 1 0.35 0.50 Comparative Example 2 0.30 0.31 Comparative Example 3 0.20 0.42 Comparative Example 4 0.28 0.40

[0156] As shown in Table 1, the gelatin content in Example 2 reached 46%, and the thickness of the guided tissue regeneration membrane after 7 days of immersion only varied by 0.02 mm. The thickness of the guided tissue regeneration membranes in Examples 1 and 3-6 remained almost unchanged after 7 days of immersion, while the thickness of the guided tissue regeneration membrane in Example 7 increased slightly. The comparison of the results in Examples 1 and 7 demonstrates that the thickness of the guided tissue regeneration membrane is also related to the molecular weight of PTMC. PTMC with a molecular weight of 150,000 or above can alleviate the thickening of the fiber membrane caused by gelatin swelling.

[0157] The guided tissue regeneration membranes of Comparative Examples 1, 3, and 4 all showed significant thickening, and cracks were observed in the membranes. Comparative Example 2 showed almost no change. Comparison of Comparative Examples 1 and 3 with Comparative Example 2 demonstrates that the guided tissue regeneration membranes swell when the gelatin content is high. Comparing Comparative Example 4 with Comparative Example 4, prepared using a blend of polycaprolactone and gelatin, showed significant thickening even at a gelatin content as low as 20%. Comparative Example 2, prepared using a blend of gelatin and PTMC, showed almost no change in thickness even at a gelatin content as high as 50%, demonstrating that the addition of PTMC significantly mitigates the problem of membrane thickening caused by gelatin swelling.

[0158] 3. Mechanical properties test

[0159] The guided tissue regeneration membranes of Examples 1-7 and Comparative Examples 1-3 were subjected to tensile strength testing according to the method of GB / T1040.3-2006. The fiber membranes were cut into 1 cm x 3 cm strips. A needle with thread was inserted through the strips 1 cm from the edge. The maximum suture force was measured using an electronic universal testing machine. The results are shown in Table 2 below.

[0160] Table 2

[0161] Sample number Tensile strength (Mpa) Maximum suture force (N) Example 1 3.5 3.2 Example 2 3.0 2.9 Example 3 2.6 2.5 Example 4 3.0 2.8 Example 5 3.1 2.4 Example 6 3.2 2.6 Example 7 3.4 3.0 Comparative Example 1 2.2 2.2 Comparative Example 2 2.0 2.1 Comparative Example 3 1.9 2.0 Comparative Example 4 2.5 2.0

[0162] As can be seen from Table 2, the guided tissue regeneration membrane of the present invention has excellent mechanical properties, especially tensile strength, which is much higher than that of Comparative Examples 1-4. In addition, the maximum suturing force of the guided tissue regeneration membrane of the present invention is 2.4-3.2N, which is also better than that of Comparative Examples 1-4. This can prevent the guided tissue regeneration membrane from tearing during suturing and thus losing its application value.

[0163] 4. Aperture test

[0164] The average pore sizes of the guided tissue regeneration membranes of Examples 1-7 and Comparative Examples 1-3 were measured using mercury intrusion porosimetry. The results are shown in Table 3 below.

[0165] Table 3

[0166] Sample number Average pore size (μm) Example 1 0.7 Example 2 0.8 Example 3 0.9 Example 4 0.6 Example 5 1.2 Example 6 0.8 Example 7 0.7 Comparative Example 1 0.2 Comparative Example 2 0.1 Comparative Example 3 3.5 Comparative Example 4 3.2

[0167] As shown in Table 3, the pore sizes of the guided tissue regeneration membranes of Comparative Examples 1 and 2 were significantly smaller than those of the guided tissue regeneration membranes of the examples. This was due to the severe shrinkage of the guided tissue regeneration membranes of Comparative Examples 1 and 2 when immersed in 95% alcohol. Furthermore, SEM observations showed a denser fiber structure and a significantly smaller pore size. The pore sizes of the guided tissue regeneration membranes of Comparative Examples 3 and 4 were significantly larger than those of the guided tissue regeneration membranes of the examples, indicating that the addition of PTMC can help reduce pore size.

[0168] 5. Adhesion test

[0169] The guided tissue regeneration membranes of Example 1 and Comparative Example 3 were tested for adhesion. The guided tissue regeneration membranes of Example 1 and Comparative Example 3 were soaked in water, and after being fully moistened, they were directly attached to the alveolar bone of dogs to observe the adhesion of the membranes. The results are as follows: Figure 5 and Figure 6 shown.

[0170] Depend on Figure 5 It can be seen that after the guided tissue regeneration membrane of Example 1 is soaked in water, it can be well attached to the alveolar bone of the dog without the need for fixation; Figure 6It can be seen that after the guided tissue regeneration membrane of Comparative Example 3 was soaked in water, its adhesion to the canine alveolar bone was significantly worse than that of Example 1, indicating that the addition of PTMC can significantly improve its adhesion.

[0171] 6. Animal experiments

[0172] The guided tissue regeneration membrane sample prepared in Example 1 was sterilized by irradiation and then used for evaluation in an animal model of tooth extraction sockets. GUIDOR, a polylactic acid-based material currently available on the market, was used as a control group.

[0173] A beagle dog was selected and fasted for 12 hours before the operation. It was anesthetized with 3% sodium pentobarbital at 1 ml / kg intravenous injection at 15°C. After anesthesia, the hair around the surgical site of the mandible was removed. The inside of the mouth and the surrounding skin were disinfected with iodine tincture and covered with a towel. The gingival flaps around the 1st, 2nd, 3rd and 4th premolars were separated to ensure the integrity of the periosteum, and the 1st, 2nd, 3rd and 4th premolars on both sides of the mandible were extracted. Bone powder mixed with autologous blood was placed in the extraction socket and squeezed appropriately to make the height of the bone powder flush with the defect surface. The repair membrane sample prepared in Example 1 and the GUIDOR control substance were covered on top of the bone powder, which served as the experimental group and the GUIDOR control group, respectively. The gums were then sutured. The specific operation process is as follows. Figure 7 shown.

[0174] During operation, it was found that the guided tissue regeneration membrane of the embodiment of the present invention 1 is soft, and in the case of not using bone screws for fixation, adhesion is also very good, firmly attached, and excellent operability. After suturing the gums, 800,000 units of penicillin sodium (intravenous infusion of penicillin sodium for the first 3 days) and 1,000,000 units of streptomycin were injected intramuscularly every day for 7 days before operation to prevent infection. Fasting was performed for 5 days after operation, and nutrition was supplemented by intravenous infusion every day (0.5 bottles / day of fat emulsion, 0.5 bottles / day of amino acids, 1 bottle / day of normal saline, and 1 bottle / day of glucose injection). On the 6th day, liquid food was fed every other day for 2 weeks. After feeding the liquid food, residual food in the wound was slowly rinsed with normal saline immediately to prevent infection.

[0175] 7 days after surgery, observe and record the surgical site every day, and use a cotton swab dipped in chlorhexidine disinfectant to gently roll and disinfect the wound. If the wound heals well, remove the sutures on the 7th-8th day, and extend the disinfection days if necessary. Continue to observe for 30 days, dissect and euthanize the animal, observe the gum condition, peel off the gums at the implant site, and observe the implant material. Use a hacksaw to remove the mandible in the bone grafting area, keep both ends of the material at least 2 cm away from the bone grafting area, ensure the integrity of the bone grafting area, carefully lift the gingival flap, and observe the bone formation in the bone grafting area. After the observation is completed, carefully peel off the soft tissue (gingival tissue and implanted material) and alveolar bone in the bone grafting area, fix the soft tissue, dehydrate and embed it into pathological sections for histopathological section observation, and observe the growth of new bone components and tissue cell penetration.

[0176] Postoperative observation:

[0177] The guided tissue regeneration membrane of Example 1 was used in the wound healing of the tooth extraction socket animal model. Figures 8-11 As shown in the left figure. Figure 8 As shown in the left picture, on the second day after surgery, the wound was rosy, normal, with little secretion, and no membrane material leakage; Figure 9 As shown in the left picture, on the 6th day after surgery, the wound was rosy and normal, and no membrane material leakage occurred; Figure 10 As shown in the left picture, on the 7th day after surgery, the wound healed well and the sutures were removed; Figure 11 As shown in the left picture, on the 30th day after surgery, the wound was completely healed.

[0178] In the anatomy experiment, Figure 12 As shown, it can be seen that after 30 days of using the guided tissue regeneration membrane of Example 1, the gums healed well, no bone powder was scattered, the bone defect position was basically healed, and the shielding effect on the soft tissue was very good. The guided tissue regeneration membrane was completely attached to the alveolar bone under the gums and there was no slippage of the membrane. The material was easily separated from the gum tissue, and the material did not show obvious thickening.

[0179] The wound healing effect of the guided tissue regeneration membrane of the GUIDOR control group after being used in the tooth extraction socket animal model is as follows Figures 8-11 As shown in the right figure. Figure 8 As shown in the right picture, on the second day after surgery, the wound was rosy and normal; Figure 9 As shown in the right picture, on the 6th day after surgery, the wound was rosy and normal; Figure 10 As shown in the right picture, on the 7th day after surgery, the wound was basically healed and the sutures were removed; Figure 11 As shown in the right figure, on the 30th day after surgery, the suture removal site was completely healed and there was no significant difference in appearance from the experimental group.

[0180] In the anatomy experiment, Figure 13 As shown, after autopsy one month after surgery, the GUIDOR control group was found to have scattered bone powder, and the bone repair effect was worse than that of Example 1. In addition, more soft tissue had penetrated and grown into the bone defect, indicating that its soft tissue shielding effect was poor.

[0181] It should be noted that, although the technical solutions of the present invention are described with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0182] While various embodiments of the present invention have been described above, the above descriptions are intended to be illustrative, non-exhaustive, and not limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is selected to best explain the principles of the embodiments, their practical applications, or technological improvements in the marketplace, or to enable others skilled in the art to understand the embodiments disclosed herein.

Claims

1. A guided tissue regeneration membrane, characterized in that: The guided tissue regeneration membrane is formed by interweaving and stacking fiber filaments and has a porous structure; wherein, The guided tissue regeneration membrane is derived from fiber raw materials, and the fiber raw materials include synthetic polymer materials and natural polymer materials; The synthetic polymer material includes non-elastic material and elastomeric material; The non-elastomeric material is a polyester compound.

2. The guided tissue regeneration membrane according to claim 1, characterized in that: The mass ratio of the non-elastic material, the natural polymer material and the elastomeric material is (0.5-2):(1-6):(1-6), preferably (0.5-1.5):(1-4.5):(1-4.5).

3. The guided tissue regeneration membrane according to claim 1 or 2, characterized in that: The polyester compound includes one or a combination of two or more of polylactic acid, polycaprolactone, polyglycolic acid, and glycolic acid-lactic acid copolymer; and / or, The natural polymer material includes one or a combination of two or more of gelatin, collagen, silk fibroin, hyaluronic acid and cellulose.

4. The guided tissue regeneration membrane according to any one of claims 1 to 3, characterized in that: The elastomeric material includes one or a combination of two or more of polytrimethylene carbonate, styrene-butadiene-styrene block copolymer, styrene-isoprene-styrene block copolymer, styrene-ethylene-butylene-styrene block copolymer, and styrene-ethylene-propylene-styrene block copolymer; preferably, the elastomeric material is polytrimethylene carbonate; further preferably, the weight average molecular weight of the polytrimethylene carbonate is greater than 150,000 Da.

5. The guided tissue regeneration membrane according to any one of claims 1 to 4, characterized in that: The fiber raw material is also doped with osteogenic induction powder.

6. The guided tissue regeneration membrane according to any one of claims 1 to 5, characterized in that: The average pore size of the guided tissue regeneration membrane is 0.1-5 μm; the tensile strength of the guided tissue regeneration membrane is 2.5-3.5 MPa; and the maximum suturing force of the guided tissue regeneration membrane is 2.4-3.2N.

7. A method for preparing a guided tissue regeneration membrane according to any one of claims 1 to 6, characterized in that: The following steps are involved: Dissolving fiber raw materials in an organic solvent to obtain a spinning solution; The film-like product is prepared by a spinning process; a step of post-treating the membrane product to obtain a guided tissue regeneration membrane; Preferably, the spinning process may include one or a combination of two or more of electrospinning technology, centrifugal spinning technology, hot melt spinning technology, and melt electrospinning technology.

8. The preparation method according to claim 7, characterized in that: In the spinning solution, the mass concentration of the fiber raw material is 5%-10%; and / or, The organic solvent includes one or a combination of two or more of hexafluoroisopropanol, trifluoroethanol, chloroform, dichloromethane, tetrahydrofuran, and N,N'-dimethylformamide; and / or, The parameters of the electrospinning technology include: adjusting the voltage of the high-voltage generator to 15-33 kV, adjusting the rate of the microinjection pump to 2-10 mL / h, adjusting the receiving distance of the receiving device to 18-24 cm, and the speed of the receiving roller to 50-500 rpm; controlling the temperature during the electrospinning process to 20-26° C. and the humidity to 60-70%.

9. The preparation method according to claim 7 or 8, characterized in that: The post-treatment includes the steps of removing residual organic solvent and / or drying; preferably, the film-like product is soaked in an alcohol solvent to remove residual organic solvent; more preferably, the soaking is performed 1-10 times.

10. Use of the guided tissue regeneration membrane according to any one of claims 1 to 6 for preparing an oral repair membrane.

Images