Biological barrier membrane as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biomedical materials, in particular to a biological barrier membrane as well as a preparation method and application thereof. The biological barrier membrane comprises a nano support membrane, a collagen membrane and a plasma matrix, wherein the nano support membrane and the collagen membrane are compounded together through the plasma matrix. The biological barrier membrane provided by the invention takes the plasma matrix as a composite material, shows excellent mechanical strength and bonding strength on the basis of having excellent stability, plasticity, biocompatibility and degradability, avoids the occurrence of displacement or peeling in surgical operation, can effectively isolate soft tissue from a bone regeneration area, and has a good application prospect. The invasion of soft tissues is prevented, so that bone regeneration and bone repair are promoted.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and particularly relates to a biological barrier membrane, a preparation method thereof, and an application thereof. Background Art

[0002] Guided Bone Regeneration (GBR) is a surgical technique widely used in oral medicine, aiming to improve the structure and function of bone defect or lesion areas by promoting the regeneration and growth of bone tissue. This technique is particularly applicable to dental implants, repair of bone injuries caused by periodontal diseases, and bone reconstruction in other maxillofacial surgeries. The key of GBR is to isolate the bone regeneration area from soft tissues through a barrier membrane, thereby providing a stable growth environment for bone cells, preventing the invasion of soft tissues, and ensuring that bone tissue can regenerate smoothly within a specific space. With the progress of technology, the barrier membrane materials for GBR have gradually transitioned from the initial non-absorbable membranes to absorbable materials to reduce the postoperative trauma of patients and the need for secondary surgeries.

[0003] However, most of the currently available absorbable biofilms still have some deficiencies, especially in terms of stability, mechanical properties, forming ability, plasticity, and bioactivity. To make up for these defects, some researchers add metal reinforcing materials such as titanium to the membrane materials to improve strength and stability. However, these membranes often require secondary surgeries for removal, increasing the surgical burden and economic cost of patients. There are also some researchers who use a composite of a metal membrane and an absorbable biofilm, and an adhesive material is needed for bonding between the two. There are mainly two commonly used adhesive materials: one is a medical glue, which belongs to chemical products, is non-degradable, and has potential toxicity; the other is a fibrin adhesive extracted from animal bodies, and its degradation period is usually about 1-2 weeks, but it belongs to xenobiotic biomaterials, and at the same time, it has low bonding strength and high cost. Moreover, since the metal membrane is on the inner side and the absorbable membrane is on the outer side, a larger amount of deformation is required on the outer side during the shaping process. In actual operation, neither of the above two adhesive materials can withstand large tensile stresses, resulting in the peeling of the metal membrane and the absorbable membrane, and poor stability and mechanical properties.

[0004] Therefore, it is desired to provide a new biological barrier membrane to solve the above problems. Summary of the Invention

[0005] To solve the above technical problems, the present invention provides a biological barrier membrane, its preparation method and application. The biological barrier membrane provided by the present invention uses plasma matrix as a composite material. On the basis of excellent stability, plasticity, biocompatibility and degradability, it also exhibits excellent mechanical strength and bonding strength, avoiding displacement or peeling during surgical operations, and can effectively isolate soft tissues from the bone regeneration area, prevent the invasion of soft tissues, and thus promote bone regeneration and bone repair.

[0006] In the first aspect, the present invention provides a biological barrier membrane, which includes a nano-supporting membrane, a collagen membrane and a plasma matrix, and the nano-supporting membrane and the collagen membrane are combined together through the plasma matrix.

[0007] The biological barrier membrane provided by the present invention uses plasma matrix as a composite material. On the basis of excellent stability, plasticity, biocompatibility and degradability, it has excellent mechanical strength and bonding strength, avoiding displacement or peeling during surgical operations, and can effectively isolate soft tissues from the bone regeneration area, prevent the invasion of soft tissues, and thus promote bone regeneration and bone repair. Specifically:

[0008] The biological barrier membrane provided by the present invention combines the nano-supporting membrane and the collagen membrane with the plasma matrix. Among them, the nano-supporting membrane has high mechanical strength, biocompatibility and stability, and can provide sufficient support for the biological barrier membrane at the initial stage of bone regeneration to ensure the stability of the biological barrier membrane. At the same time, it can be personalized shaped according to the wound area and bone morphology of the patient to ensure a stable bone regeneration space at different bone defect sites. Moreover, the nano-supporting membrane is degradable and gradually degrades in the later stage of bone regeneration. On the one hand, it provides space for bone regeneration. On the other hand, the degradation products released by it not only do not have an adverse impact on bone tissue, but can promote the proliferation, calcification of osteoblasts and the repair of bone tissue, further accelerating the process of bone regeneration. The collagen membrane has good biocompatibility and the ability to promote cell adhesion and growth. At the same time, it can effectively prevent soft tissues from invading the bone regeneration area, provide necessary support for the surrounding bone tissue, provide a suitable growth environment for osteocytes, and promote bone regeneration and bone repair. The plasma matrix has good toughness. On the one hand, it can crosslink with the collagen fibers in the collagen membrane to form a stable structure. On the other hand, the hydrophilic nano-supporting membrane can adsorb fibrinogen in the plasma matrix and crosslink into fibrin on the surface, using the plasma matrix to combine the nano-supporting membrane and the collagen membrane together. The final product has excellent mechanical strength and bonding performance, effectively avoiding the displacement or peeling of the nano-supporting membrane and the collagen membrane during surgical operations. At the same time, because the plasma matrix is a patient's autologous material, it is safer. Combining with the effective isolation of soft tissues and the bone regeneration area, it promotes bone regeneration and bone repair, thus providing a more efficient, stable and precisely controllable innovative solution for guided bone regeneration.

[0009] As a preferred technical solution of the present invention, the biological barrier membrane further includes a plasma matrix surface layer that wraps the nano-supporting membrane, the collagen membrane, and the plasma matrix.

[0010] The biological barrier membrane provided by the present invention also has a plasma matrix surface layer on the surfaces of the nano-supporting membrane, the collagen membrane, and the plasma matrix, that is, the nano-supporting membrane, the collagen membrane, and the plasma matrix are encapsulated by the plasma matrix surface layer. In this way, the combined effect of bonding and encapsulation can further ensure the relative stability of the nano-supporting membrane and the collagen membrane, and has more excellent mechanical strength and bonding strength, ensuring more convenient use in clinical applications, without displacement or shedding, guaranteeing the successful progress of the operation, more effectively isolating soft tissues from the bone regeneration area, and promoting bone regeneration and bone repair.

[0011] As a preferred technical solution of the present invention, the composition of the nano-supporting membrane includes biodegradable nano-materials, and the biodegradable nano-materials include any one or more of magnesium, calcium, zinc and their alloys, alumina, and titanium oxide.

[0012] The composition of the nano-supporting layer of the present invention is biodegradable nano-materials with excellent degradability, mechanical strength, and biocompatibility, which can gradually degrade under specific conditions and release beneficial metal ions, not only providing precise biochemical stimulation for the proliferation and osteogenic activity of bone cells, but also avoiding the biological adverse reactions caused by the premature degradation of traditional metal materials. Moreover, the surface microstructures of the nano-supporting membrane, such as nano-pores and nano-fibrillation, can effectively enhance the mechanical strength and surface energy of the material, and promote cell adhesion and growth.

[0013] As a preferred technical solution of the present invention, the composition of the collagen membrane includes any one or more of type I collagen, porcine pericardium, peritoneum, and small intestinal submucosa.

[0014] The composition of the collagen membrane of the present invention has excellent biocompatibility, isolation barrier effect, and excellent cell adhesion.

[0015] As a preferred technical solution of the present invention, the thickness of the nano-supporting membrane is 20 - 300 μm, such as 20 μm, 50 μm, 80 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, etc.

[0016] By controlling the thickness of the nano-supporting membrane within the above range, the present invention, on the one hand, provides sufficient supporting strength for the biological barrier membrane, and on the other hand, balances with the biodegradation performance, avoiding excessive hardness from affecting the natural growth of bone tissue. Moreover, its thickness also matches the thickness of the collagen membrane, ensuring gradual degradation at the same time as the collagen membrane and forming an ideal bone regeneration space.

[0017] As a preferred technical solution of the present invention, the thickness of the collagen membrane is 0.2 - 1 mm, such as 0.2 mm, 0.4 mm, 0.6 mm, 0.8 mm, 1 mm, etc.

[0018] By controlling the thickness of the collagen membrane within the above range, the present invention can effectively prevent soft tissues from invading the bone regeneration area, provide a suitable growth environment for bone cells, and thus promote bone regeneration.

[0019] As a preferred technical solution of the present invention, the thickness of the biological barrier membrane is 0.3 - 2.0 mm, such as 0.3 mm, 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm, etc.

[0020] In the present invention, by controlling the thickness of the biological barrier membrane within the above range, the plasma matrix can fully play a cross-linking role to composite the nano-supporting membrane and the collagen membrane together, so that the obtained biological barrier membrane has good toughness and stability on the basis of excellent mechanical support, plasticity and controllable degradability, avoids displacement or peeling that may occur during surgical operations, provides an ideal microenvironment for bone regeneration, and greatly improves the effect and speed of bone repair.

[0021] In the second aspect, the present invention provides a preparation method of the biological barrier membrane described in the first aspect, and the preparation method includes: preparing a nano-supporting membrane and a collagen membrane, and then placing the nano-supporting membrane and the collagen membrane in a liquid plasma matrix, and performing pressing after the liquid plasma matrix solidifies to obtain the biological barrier membrane.

[0022] In the preparation method provided by the present invention, the preparation methods of the nano-supporting membrane and the collagen membrane are not particularly limited. The nano-supporting membrane and the collagen membrane can be prepared separately, and then the two are placed in a liquid plasma matrix to prepare the biological barrier membrane, or a composite membrane of the nano-supporting membrane and the collagen membrane can be prepared first, and then the composite membrane is placed in a liquid plasma matrix to prepare the biological barrier membrane.

[0023] As a preferred technical solution of the present invention, the collagen membrane is a collagen membrane after pretreatment to enhance the binding force between the collagen membrane and the nano-supporting membrane. The pretreatment methods include but are not limited to surface oxidation, chemical crosslinking, and charge regulation. The surface oxidation refers to oxidizing the surface of the collagen membrane with gases such as oxygen to increase surface hydrophilicity, thereby promoting the attachment of the nano-supporting membrane and fibrin in the plasma matrix. The chemical crosslinking refers to crosslinking the surface of the collagen membrane with chemical crosslinking agents such as glutaraldehyde, epoxide compounds, or amino silanes to enhance the structural stability of the collagen membrane and improve its binding force with the nano-supporting membrane and plasma matrix. The charge regulation refers to changing the charge properties of the surface of the collagen membrane through ionization treatment or electrophoresis technology to enhance the electrostatic adsorption force on the surfaces of the nano-supporting membrane, collagen membrane, and plasma matrix.

[0024] As a preferred technical solution of the present invention, the preparation methods of the nano-supporting membrane include solution spraying method, laser spraying method, laser-induced precursor deposition method, electrospinning method, and self-assembly method.

[0025] The present invention selects a suitable preparation method according to different material characteristics and film layer requirements, and provides stable mechanical support for the biological barrier membrane and promotes the proliferation and osteogenesis of osteocytes by precisely controlling the composition, thickness, uniformity, and degradation rate of the film layer.

[0026] Among them, the solution spraying method is a common and efficient coating technology suitable for the uniform coating of nano-materials such as metals and ceramics, and includes the following steps:

[0027] Dissolve the nano-supporting membrane precursor in a solvent to obtain a precursor solution, uniformly spray the precursor solution onto the surface of the collagen membrane, and dry to obtain the nano-supporting membrane.

[0028] As a preferred technical solution of the present invention, the solvent is selected from water or ethanol to ensure that the precursor can be completely dissolved and uniformly dispersed.

[0029] As a preferred technical solution of the present invention, the nano-supporting membrane precursor includes magnesium salts, zinc salts, titanium compounds, alumina, titanium oxide, calcium phosphate-based materials.

[0030] As a preferred technical solution of the present invention, the spraying is carried out using a pneumatic spray or ultrasonic spraying device, and the spraying distance, angle, speed, and coating thickness need to be precisely controlled.

[0031] As a preferred technical solution of the present invention, the drying is carried out using a hot air or vacuum drying oven to form a nano-structure of the coating and remove solvent residues, which helps to improve the mechanical strength and structural stability of the nano-supporting membrane.

[0032] The laser spraying method vaporizes powders or precursors through a high-power laser to form a coating. This method can achieve high-quality coating deposition in a relatively short time and includes the following steps:

[0033] Focus the laser source on the nano-supporting membrane precursor powder. Instantly heat and vaporize the powder through a high-energy laser to form a plasma, and deposit it on the surface of the collagen membrane through gas flow transportation. Cool and solidify to obtain the nano-supporting membrane.

[0034] As a preferred technical solution of the present invention, the nano-supporting membrane precursor powder includes magnesium powder, zinc powder, alumina powder, titanium oxide powder, etc.

[0035] The laser-induced precursor deposition method uses a laser to focus on a precursor solution or gas source, and induces the deposition of metals or ceramics through a photoreaction, including the following steps:

[0036] Prepare a nano-supporting membrane precursor solution. Focus the laser on the surface of the precursor solution. The nanoparticles generated by the decomposition of the precursor are deposited on the surface of the collagen membrane to obtain the nano-supporting membrane.

[0037] This method can adjust the thickness and structure of the supporting membrane by controlling the energy of the laser, the irradiation time, and the concentration of the precursor solution. The nano-supporting membrane precursor solution includes organometallic compound solutions of magnesium, zinc and their alloys, alumina, and titanium oxide.

[0038] The electrospinning method drives a nano-supporting membrane precursor solution to form a nanofiber network on the surface of a collagen membrane through an electric field, including the following steps:

[0039] Prepare an electrospinning solution containing a nano-supporting membrane precursor. Inject the solution into the nozzle of the electrospinning device, apply a high voltage, stretch the solution into nanofibers using the electric field, and guide their deposition on the surface of the collagen membrane through the electric field. Dry and crosslink to obtain the nano-supporting membrane.

[0040] This method collects fibers through a receiver to ensure the uniformity of the supporting membrane and the nanofiber structure at the nanoscale. The collected nano-supporting membrane can be processed to enhance its stability and mechanical strength. The electrospinning solution generally uses a fluorinated solvent to obtain suitable electrospinning properties. The nano-supporting membrane precursor includes alumina, titanium oxide, etc.

[0041] The self-assembly method promotes the spontaneous formation of an ordered structure on the surface of the collagen membrane substrate by controlling the interaction of material molecules, including the following steps:

[0042] Place the nano - support membrane precursor in a solvent, add a surfactant or molecular template, and by adjusting conditions such as solution concentration, temperature, pH value, etc., promote the ordered arrangement of molecules or nanoparticles in the solution, guide the precursor molecules to spontaneously form a nano - coating on the surface of the collagen membrane, and cure it to obtain the nano - support membrane.

[0043] In this method, the self - assembled coating is cured by physical or chemical methods, which can effectively enhance its mechanical stability and biocompatibility. The nano - support membrane precursor includes magnesium, zinc, titanium oxide, aluminum oxide, calcium phosphate, etc.

[0044] The preparation method of the nano - support membrane provided by the present invention can precisely control the thickness, uniformity, degradation characteristics and biological activity of the membrane layer according to actual needs. In the later stage of preparing some materials and membrane layers, pressing technology can be combined to tightly bond the nano - support membrane and the collagen membrane to form a more stable composite structure. Each method has its unique advantages, and the most suitable preparation process can be selected according to specific applications to ensure the high performance and excellent bone regeneration support effect of the final membrane material.

[0045] As a preferred technical solution of the present invention, the nano - support membrane also undergoes post - treatment, and the post - treatment includes cleaning, passivation treatment and heat treatment to remove residual chemical substances or unreacted metal precursors and ensure the effect of passivation treatment.

[0046] Among them, the method of cleaning is to clean the membrane surface with deionized water or organic solvents to remove unbound metal particles and residual organic solvents. The method of passivation treatment is to perform passivation treatment on the surface of the membrane layer, such as using chemical solutions such as hydrofluoric acid and phosphates to form a stable metal oxide film, thereby regulating the degradation rate of the nano - support membrane and improving the biocompatibility of the membrane surface. Passivation treatment can also enhance the chemical stability of the membrane layer and prevent the metal from degrading too quickly in the body. The method of heat treatment is to perform high - temperature treatment on the membrane to enhance the crystallinity and structural stability of the nano - support membrane, and at the same time help to remove the solvent and promote the improvement of the density and mechanical strength of the membrane layer.

[0047] As a preferred technical solution of the present invention, the liquid plasma matrix is the liquid plasma matrix obtained by centrifuging blood.

[0048] As a preferred technical solution of the present invention, the centrifugal force of the centrifugation is 50 - 3000g, such as 50g, 100g, 500g, 1000g, 2000g, 3000g, etc., and preferably 1500g.

[0049] As a preferred technical solution of the present invention, the centrifugation time is 1 - 20min, such as 1min, 3min, 5min, 10min, 15min, 20min, etc., and preferably 3min.

[0050] The present invention centrifuges blood and controls the centrifugal force and centrifugal time to obtain a plasma matrix. At this time, the fibrin in the obtained plasma matrix is not fully cross-linked and remains in a liquid state. The collagen membrane and the nano-supporting membrane are directly and completely immersed in the liquid plasma matrix using a mold. After about 5 minutes, the liquid plasma matrix will completely solidify, and then through pressing into a film, the biological barrier film is obtained.

[0051] As a preferred technical solution of the present invention, the pressure during pressing is 0.5 - 5 N, such as 0.5 N, 1 N, 2 N, 3 N, 4 N, 5 N, etc.

[0052] As a preferred technical solution of the present invention, the time during pressing is 1 - 5 min, such as 1 min, 2 min, 3 min, 4 min, 5 min, etc.

[0053] In a third aspect, the present invention provides the application of the biological barrier film described in the first aspect or the biological barrier film prepared by the preparation method described in the second aspect as a bone repair material.

[0054] The biological barrier film provided by the present invention provides a material solution with revolutionary progress for the field of guided bone regeneration, and has broad application prospects, especially in dental implants, bone defect repair and other bone regeneration-related fields.

[0055] The technical solution provided by the embodiment of the present invention has the following advantages compared with the prior art:

[0056] The biological barrier film provided by the present invention uses a plasma matrix as a composite material. On the basis of having excellent stability, plasticity, biocompatibility and degradability, it also exhibits excellent mechanical strength and bonding strength, avoiding the occurrence of displacement or peeling during surgical operations, and can effectively isolate soft tissues from the bone regeneration area, prevent the invasion of soft tissues, and thus promote bone regeneration and bone repair. Detailed Embodiments

[0057] In order to more clearly understand the above objects, features and advantages of the present invention, the solution of the present invention will be further described below. It should be noted that, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

[0058] Many specific details are set forth in the following description in order to fully understand the present invention, but the present invention can also be implemented in other ways different from those described herein; obviously, the embodiments in the specification are only a part of the embodiments of the present invention, rather than all the embodiments.

[0059] Example 1

[0060] This embodiment provides a biological barrier membrane and a preparation method thereof. The preparation method includes:

[0061] (1) Select a magnesium alloy AZ31 sheet with a thickness of 0.1 mm. Place the magnesium alloy sheet in an ultrasonic cleaner, clean it with 100% ethanol for 5 minutes, and then clean it with distilled water for 5 minutes to remove surface dirt. After cleaning, dry the magnesium alloy sheet with a clean paper towel.

[0062] (2) Use a femtosecond laser cutting device (such as Tianyu Laser Femtosecond Laser) to cut the magnesium alloy plate. The power is set to 5 W, the pulse frequency is 50 Hz, and the cutting speed is set to 2 mm / s. After laser cutting, a diamond grid pattern is formed. The grid aperture is 1 mm, the edge distance is 2 mm, and during the cutting process, pay attention to keeping the distance between the laser focus and the material surface at 1 mm.

[0063] (3) Immerse the magnesium alloy grid in a 20% HF solution at 37 °C for 6 hours to form a MgF2 passivation layer. After passivation, immediately take out the magnesium alloy sheet and clean it with 100% ethanol and distilled water for 10 minutes each to remove the residual solution.

[0064] (4) Place the porcine pericardium (with a thickness of 2 mm) and the magnesium alloy grid in appropriate positions. Use the pressing method to combine the two, apply a pressure of 2 MPa, and the pressing time is 5 minutes to ensure that the porcine pericardium and the magnesium mesh form a tight combination, which is recorded as the composite membrane of porcine pericardium and magnesium mesh.

[0065] (5) Collect 60 mL of venous blood from the cubital fossa of 1 volunteer into a glass blood collection tube, ensure its sterility and negative pressure state, quickly place it in a horizontal centrifuge and centrifuge at 1500 g for 3 min to separate the upper liquid plasma matrix. Immerse the composite membrane of porcine pericardium and magnesium mesh in step (4) completely into the liquid plasma matrix. After the plasma matrix solidifies, press it with a pressure of 1 N for 2 min to obtain the biological barrier membrane with a thickness of 1.5 mm.

[0066] Example 2

[0067] This embodiment provides a biological barrier membrane and a preparation method thereof. The preparation method includes:

[0068] (1) Select a zinc foil with a purity of 99.998% and a thickness of 0.1 mm.

[0069] (2) Use laser cutting technology (such as TRUMPF CO2 laser cutting machine) to make the zinc foil into a zinc membrane with pores. The pore diameter is set to 300 μm, and the adjacent distance between pores is 1.2 mm. The cutting power is 10 W, and the cutting speed is 5 mm / s to ensure uniform pore distribution.

[0070] (3) Immerse all zinc film samples successively in acetone, absolute ethanol, and distilled water for cleaning, with each solvent cleaning time being 10 minutes. After cleaning, dry them with a clean paper towel.

[0071] (4) Place the porcine pericardium (with a thickness of 2 mm) and the zinc film together, and use the pressing method to combine the two, applying a pressure of 2 MPa for a pressing time of 5 minutes to ensure tight combination of the two, denoted as the composite film of porcine pericardium and zinc film.

[0072] (5) Collect 40 mL of venous blood from the cubital fossa of 1 volunteer into a glass blood collection tube, ensuring its aseptic and negative pressure state. Quickly place it in a horizontal centrifuge and centrifuge at 700 g for 12 min to separate the upper liquid plasma matrix. Immerse the composite film of porcine pericardium and zinc film in step (4) completely into the liquid plasma matrix. After the plasma matrix solidifies, press it with a pressure of 2 N for 1 min to obtain the biological barrier film with a thickness of 1.7 mm.

[0073] Example 3

[0074] This example provides a biological barrier film and its preparation method. The preparation method includes:

[0075] (1) Dissolve titanium tetraisopropoxide in absolute ethanol at a concentration of 1.5 moL / L, add a small amount of deionized water and concentrated hydrochloric acid for hydrolysis reaction, and stir for 30 minutes until the solution is clear and uniform.

[0076] (2) Use a fiber laser system (such as a YAG laser), set the power to 50 W, the wavelength to 1064 nm, the laser pulse frequency to 10 Hz, and the laser focus distance from the sample surface to 5 mm. Irradiate the solution with the laser light source to stimulate the decomposition of titanium tetraisopropoxide, generating titanium oxide nanoparticles and depositing them on the surface of the type I collagen film (with a thickness of 0.3 mm). The laser irradiation duration is 5 minutes to ensure that the titanium oxide precursor decomposes fully on the film surface to generate titanium oxide nanoparticles, and pause for 10 seconds after each irradiation to ensure complete decomposition of the precursor.

[0077] (3) After the coating deposition is completed, the sample is gradually cooled to room temperature through a temperature control system at a cooling rate of 10 °C / min. To ensure the stability and adhesion of the titanium oxide film layer, place the film layer sample in an oven with the temperature set to 350 °C and a curing time of 1 hour to enhance the durability of the film layer, denoted as the composite film of titanium oxide film and collagen film, and the thickness of the titanium oxide film layer is 0.3 mm.

[0078] (4) Collect 36 mL of venous blood from the cubital fossa of 1 volunteer into a glass blood collection tube, ensure its aseptic and negative pressure state, quickly place it in a horizontal centrifuge and centrifuge at 1200 g for 6 min to separate the upper liquid plasma matrix. Immerse the titanium oxide film and collagen film composite membrane obtained in step (3) completely into the liquid plasma matrix. After the plasma matrix solidifies, press it at a pressure of 1 N for 2 min to obtain the biological barrier membrane with a thickness of 0.6 mm.

[0079] Comparative Example 1

[0080] This comparative example provides a composite membrane of porcine pericardium and magnesium mesh, and its preparation method is the same as steps (1)-(5) of Example 1.

[0081] Comparative Example 2

[0082] This comparative example provides a composite membrane of porcine pericardium and zinc membrane, and its preparation method is the same as steps (1)-(5) of Example 2.

[0083] Performance Test

[0084] Test the bonding strength of the barrier membranes prepared in the examples and comparative examples. Among them, the test results are shown in Table 1:

[0085] Table 1

[0086] Sample Bond strength (KPa) Example 1 72.1 Example 2 69.4 Comparative Example 1 3.9 Comparative Example 2 2.5

[0087] It can be found from the results in Table 1 that the bonding strength of the biological barrier membrane prepared by using plasma matrix as a composite material in the present invention is significantly improved, and it can effectively avoid displacement or shedding during actual operation, ensuring the successful progress of the operation.

[0088] It should be noted that in this article, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements not only includes those elements, but also includes other elements not expressly listed, or also includes elements inherent to such process, method, article or device. Without further limitation, an element defined by the statement "including a..." does not exclude the existence of additional identical elements in the process, method, article or device including the said element.

[0089] The above are only specific embodiments of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments described herein, but rather to the broadest scope consistent with the principles and novel features disclosed herein.

Claims

1. A biological barrier membrane, characterized in that: The biological barrier membrane comprises a nano-support membrane, a collagen membrane and a plasma matrix, and the nano-support membrane and the collagen membrane are compounded together through the plasma matrix.

2. The biological barrier membrane according to claim 1, characterized in that The biological barrier membrane also includes a plasma matrix surface layer that wraps the nano support membrane, the collagen membrane and the plasma matrix.

3. The biological barrier membrane according to claim 1 or 2, characterized in that: The components of the nano support membrane include biodegradable nano materials, and the biodegradable nano materials include any one or more of magnesium, calcium, zinc and alloys thereof, aluminum oxide, and titanium oxide; And / or, the components of the collagen membrane include any one or more of type I collagen, porcine pericardium, peritoneum and small intestinal submucosa.

4. The biological barrier membrane according to any one of claims 1 to 3, characterized in that The thickness of the nano support film is 20-300 μm; And / or, the thickness of the collagen membrane is 0.2-1 mm; And / or, the thickness of the biological barrier membrane is 0.3-2.0 mm.

5. The method for preparing the biological barrier membrane according to any one of claims 1 to 4, characterized in that: The preparation method comprises: preparing a nano support membrane and a collagen membrane, then placing the nano support membrane and the collagen membrane in a liquid plasma matrix, and pressing the liquid plasma matrix after solidification to obtain the biological barrier membrane.

6. The preparation method according to claim 5, characterized in that: The liquid plasma matrix is ​​a liquid plasma matrix obtained by centrifuging blood.

7. The preparation method according to claim 6, characterized in that: The centrifugal force of the centrifugation is 50-3000g, preferably 1500g; And / or, the centrifugation time is 1-20 min, preferably 3 min.

8. The preparation method according to any one of claims 5 to 7, characterized in that: The pressure during the pressing is 0.5-5N; And / or, the pressing time is 1-5 min.

9. Use of the biological barrier membrane according to any one of claims 1 to 4 or the biological barrier membrane prepared by the preparation method according to any one of claims 5 to 8 as a bone repair material.