Magnesium metal film for selectively guiding tissue regeneration and preparation method thereof

Abstract

The invention provides a magnesium metal film for selectively guiding tissue regeneration and a preparation method of the magnesium metal film, and belongs to the technical field of biomedicine. The magnesium metal film for selectively guiding tissue regeneration comprises a magnesium matrix, a magnesium fluoride coating, a fluorinated hydroxyapatite coating and a polymer coating, wherein the magnesium fluoride coating and the fluorinated hydroxyapatite coating are sequentially coated on the surface of the magnesium matrix, and the polymer coating is coated on one side of the fluorinated hydroxyapatite coating. By arranging the multiple coatings on the surface of the magnesium matrix, the degradation rate of magnesium metal can be greatly reduced; the magnesium fluoride coating can improve the binding force between the magnesium matrix and the fluorinated hydroxyapatite coating; the fluorinated hydroxyapatite coating is arranged on one side of the magnesium metal film for selectively guiding tissue regeneration, the surface of the magnesium metal film is relatively rough, cell adhesion is facilitated, tissue regeneration is promoted, and the effect of selectively guiding tissue regeneration is achieved; the polymer coating is arranged on the other side, the surface is relatively smooth, and epithelial cells or fibrous connective tissues can be prevented from entering the wound surface too early to interfere the healing process.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a magnesium metal film for selectively guiding tissue regeneration and a preparation method thereof. Background Art

[0002] Currently, guided bone regeneration technology is one of the main ways to treat alveolar bone defects in clinic. The key to this technology is to guide tissue regeneration membrane, which uses its physical barrier function to isolate tissue from surrounding tissue and maintain a space that is conducive to tissue regeneration.

[0003] Magnesium metal has good biocompatibility and mechanical properties, is degradable in the human body, and has certain antibacterial ability, can provide good bone tissue growth space, and does not require secondary surgery to remove; in addition, magnesium metal also has excellent osteogenic properties, and is an ideal material for oral guided tissue regeneration membrane. However, the degradation rate of magnesium metal is too fast at present, and controlling its degradation rate is the key to oral guided tissue regeneration membrane. Patent CN106492271A provides a method for preparing an antibacterial and osteogenic dual-function guided bone regeneration absorbable membrane, which slows down its degradation rate by modifying a calcium-phosphorus coating on the surface of magnesium metal, and loading nanosilver and BMP-2 in the calcium-phosphorus coating, so that it can release nanosilver after GBR surgery to achieve a good antibacterial effect, but the antibacterial layer covers the outside of the osteogenic coating, affecting the initial bone tissue regeneration effect, and the degradation rate is still too fast. Therefore, how to slow down the degradation rate of magnesium metal and promote tissue regeneration has become a technical problem that needs to be solved in this field. Summary of the invention

[0004] The purpose of the present invention is to provide a magnesium metal film for selectively guiding tissue regeneration and a preparation method thereof. The magnesium metal film for selectively guiding tissue regeneration provided by the present invention can not only significantly slow down the degradation rate of magnesium metal, but also selectively guide tissue regeneration.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The invention provides a magnesium metal film for selectively guiding tissue regeneration, comprising a magnesium substrate, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the magnesium substrate, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating.

[0007] Preferably, the thickness of the magnesium substrate is 0.15-0.5 mm.

[0008] Preferably, the magnesium fluoride coating has a thickness of 3 to 4 μm.

[0009] Preferably, the thickness of the fluorinated hydroxyapatite coating is 1.5-2.5 μm.

[0010] Preferably, the polymer coating has a thickness of 3 to 50 μm.

[0011] Preferably, the polymer coating is made of at least one of PLLA, PDO and PPDO.

[0012] The present invention also provides a method for preparing the magnesium metal film for selectively guiding tissue regeneration described in the above technical solution, comprising the following steps:

[0013] (1) mixing a magnesium substrate with a hydrofluoric acid solution to perform a replacement reaction to obtain a magnesium substrate having a magnesium fluoride coating;

[0014] (2) mixing the magnesium substrate with the magnesium fluoride coating obtained in step (1), a calcium nitrate solution and an ammonium dihydrogen phosphate solution, and performing a precipitation reaction to obtain a magnesium substrate with a fluorinated hydroxyapatite coating;

[0015] (3) coating a polymer on one surface of the magnesium substrate having the fluorinated hydroxyapatite coating obtained in step (2) to obtain a magnesium metal film that selectively guides tissue regeneration.

[0016] Preferably, the temperature of the replacement reaction in step (1) is 20-40° C., and the time of the replacement reaction is 45 min-6 h.

[0017] Preferably, in the step (2), the molar ratio of calcium in the calcium nitrate solution to phosphorus in the diammonium phosphate solution is (1.1-1.85):1; the temperature of the precipitation reaction in the step (2) is 80-95° C., and the time of the precipitation reaction is 45 min-2 h.

[0018] Preferably, the coating in step (3) is ultrasonic spraying; the number of ultrasonic spraying is 5 to 50 times, the speed of ultrasonic spraying is 5 to 30 mm / s, and the flow rate of ultrasonic spraying is 0.15 to 0.5 mL / min.

[0019] The present invention provides a magnesium metal film for selectively guiding tissue regeneration, comprising a magnesium substrate, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the magnesium substrate, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating. The present invention can significantly slow down the degradation rate of magnesium metal by arranging a multilayer coating on the surface of the magnesium substrate; the magnesium fluoride coating can improve the bonding force between the magnesium substrate and the fluorinated hydroxyapatite coating; one side of the magnesium metal film for selectively guiding tissue regeneration is a fluorinated hydroxyapatite coating, the surface of which is relatively rough, which is conducive to cell adhesion, promotes tissue regeneration, and plays the effect of selectively guiding tissue regeneration; the other side of the magnesium metal film for selectively guiding tissue regeneration is a polymer coating, the surface of which is relatively smooth, which can prevent epithelial cells or fibrous connective tissue from entering the wound surface too early to interfere with the healing process. The experimental results show that the surface of the fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration provided by the present invention is relatively rough, which is conducive to cell adhesion and promotes tissue regeneration; the magnesium metal film is placed in 200 mL PBS buffer (pH 7.40) and immersed at 37°C for three days, with a pH value of 7.43-7.47, which effectively slows down the degradation rate of magnesium metal. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a schematic diagram of the structure of the pure magnesium flake in Example 1;

[0021] Figure 2 This is a three-dimensional diagram of the homemade oral guided tissue regeneration membrane shaping forceps in Example 1; in the figure, 1 is the forceps head, 2 is the forceps handle, 3 is the spring, 4 is the fixing screw, and 5 is the nut;

[0022] Figure 3 This is a macroscopic image of the magnesium metal film for selectively guiding tissue regeneration prepared in Example 1;

[0023] Figure 4 This is a SEM image of the fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration prepared in Example 1;

[0024] Figure 5 This is a SEM image of the fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration prepared in Example 2;

[0025] Figure 6 This is a macroscopic picture of the pure magnesium sheet with a three-dimensional shape and bright surface prepared in Comparative Example 1. DETAILED DESCRIPTION

[0026] The invention provides a magnesium metal film for selectively guiding tissue regeneration, comprising a magnesium substrate, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the magnesium substrate, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating.

[0027] The magnesium metal film for selectively guiding tissue regeneration provided by the present invention comprises a magnesium matrix. The present invention adopts the magnesium matrix as the matrix material, has good mechanical properties, and can provide a certain growth space for the tissue.

[0028] In the present invention, the magnesium substrate is preferably a magnesium metal sheet; the thickness of the magnesium substrate is preferably 0.15 to 0.5 mm, more preferably 0.20 to 0.35 mm.

[0029] The present invention has no special limitation on the size of the magnesium substrate, which can be adjusted according to actual needs.

[0030] In the present invention, the magnesium substrate is preferably provided with a large circular hole and a small circular hole; the aperture of the large circular hole is preferably matched with the base; the diameter of the large circular hole is preferably 2.0-3.0 mm; the small circular hole is preferably matched with the membrane pin; the diameter of the small circular hole is preferably 0.8-2.0 mm. The present invention has no special limitation on the positions of the large circular hole and the small circular hole, which can be determined according to the positions of the base and the membrane pin.

[0031] In the present invention, the magnesium matrix is ​​preferably pure magnesium, magnesium-zinc alloy or magnesium-zinc-calcium alloy; the mass content of Mg in the pure magnesium is preferably ≥99.98%; the mass content of zinc in the magnesium-zinc alloy is preferably 1-6%; the mass content of magnesium in the magnesium-zinc alloy is preferably ≥93.5%; the mass content of calcium in the magnesium-zinc-calcium alloy is preferably 0.2-1%; the mass content of zinc in the magnesium-zinc-calcium alloy is preferably 1-5%; the mass content of magnesium in the magnesium-zinc-calcium alloy is preferably ≥93.5%.

[0032] In the present invention, the magnesium metal film for selectively guiding tissue regeneration further comprises a magnesium fluoride coating coated on the surface of the magnesium substrate. In the present invention, the magnesium fluoride coating can improve the bonding force between the magnesium substrate and the fluorinated hydroxyapatite coating.

[0033] In the present invention, the thickness of the magnesium fluoride coating is preferably 3-4 μm, more preferably 3.5-4 μm. In the present invention, limiting the thickness of the magnesium fluoride coating to the above range can further slow down the degradation rate of magnesium metal.

[0034] In the present invention, the magnesium metal film for selectively guiding tissue regeneration further comprises a fluorinated hydroxyapatite coating coated on the surface of the magnesium fluoride coating. In the present invention, the surface of the fluorinated hydroxyapatite coating is relatively rough, which is conducive to cell adhesion, promotes tissue regeneration, and achieves the effect of selectively guiding tissue regeneration.

[0035] In the present invention, the thickness of the fluorinated hydroxyapatite coating is preferably 1.5 to 2.5 μm, more preferably 2.0 to 2.5 μm. In the present invention, limiting the thickness of the fluorinated hydroxyapatite coating to the above range can further slow down the degradation rate of magnesium metal.

[0036] In the present invention, the magnesium metal film for selectively guiding tissue regeneration further comprises a polymer coating coated on one side of the fluorinated hydroxyapatite coating. In the present invention, the surface of the polymer coating is relatively smooth, which can prevent epithelial cells or fibrous connective tissue from entering the wound surface prematurely and interfering with the healing process.

[0037] In the present invention, the thickness of the polymer coating is preferably 3-50 μm, more preferably 5-30 μm, and more preferably 10-20 μm. In the present invention, limiting the thickness of the polymer coating to the above range can further slow down the degradation rate of magnesium metal.

[0038] In the present invention, the material of the polymer coating is preferably at least one of PLLA, PDO and PPDO; the weight average molecular weight M of the PLLA, PDO and PPDO is w Preferably it is 100,000 to 300,000.

[0039] The present invention can significantly slow down the degradation rate of magnesium metal by arranging a multi-layer coating on the surface of a magnesium substrate; the magnesium fluoride coating can improve the bonding force between the magnesium substrate and the fluorinated hydroxyapatite coating; one side of the magnesium metal film for selectively guiding tissue regeneration is the fluorinated hydroxyapatite coating, the surface of which is relatively rough, which is conducive to cell adhesion, promotes tissue regeneration, and plays an effect of selectively guiding tissue regeneration; the other side of the magnesium metal film for selectively guiding tissue regeneration is a polymer coating, the surface of which is relatively smooth, which can prevent epithelial cells or fibrous connective tissue from entering the wound surface too early to interfere with the healing process.

[0040] The magnesium metal film for selectively guiding tissue regeneration provided by the present invention is double-sided heterogeneous, with a polymer coating on the outside and a fluorinated hydroxyapatite coating on the inside. On the one hand, the degradation rate of the magnesium metal for selectively guiding tissue regeneration can be slowed down; on the other hand, the polymer coating has a certain thickness and a relatively smooth surface, which can prevent epithelial cells or fibrous connective tissue from entering the wound surface too early to interfere with the healing process; the surface of the fluorinated hydroxyapatite coating is relatively rough, which is conducive to cell adhesion, promotes tissue regeneration, and plays an effect of selectively guiding tissue regeneration; the magnesium metal film for selectively guiding tissue regeneration has good mechanical properties, can provide a certain growth space for tissue, has good biocompatibility, and can be self-degraded in the human body without the need for secondary removal.

[0041] The present invention also provides a method for preparing the magnesium metal film for selectively guiding tissue regeneration described in the above technical solution, comprising the following steps:

[0042] (1) mixing a magnesium substrate with a hydrofluoric acid solution to perform a replacement reaction to obtain a magnesium substrate having a magnesium fluoride coating;

[0043] (2) mixing the magnesium substrate with the magnesium fluoride coating obtained in step (1), a calcium nitrate solution and an ammonium dihydrogen phosphate solution, and performing a precipitation reaction to obtain a magnesium substrate with a fluorinated hydroxyapatite coating;

[0044] (3) coating a polymer on one surface of the magnesium substrate having the fluorinated hydroxyapatite coating obtained in step (2) to obtain a magnesium metal film that selectively guides tissue regeneration.

[0045] The present invention has no particular limitation on the sources of the raw materials, and commercially available products known to those skilled in the art may be used.

[0046] The invention mixes a magnesium substrate with a hydrofluoric acid solution and performs a replacement reaction to obtain a magnesium substrate with a magnesium fluoride coating. In the invention, magnesium reacts with hydrofluoric acid to obtain magnesium fluoride.

[0047] In the present invention, the magnesium substrate is preferably laser cut, polished, cleaned and dried in sequence before use. The present invention sequentially laser cuts, polishes, cleans and dries the magnesium substrate to remove oxide layers or impurities on the surface of the magnesium substrate.

[0048] The present invention has no special limitation on the laser cutting, polishing, cleaning and drying operations, and operations well known to those skilled in the art may be adopted.

[0049] In the present invention, the mass concentration of the hydrofluoric acid solution is preferably 12 to 40%, more preferably 12 to 20%. The present invention limits the mass concentration of the hydrofluoric acid solution to the above range, which is beneficial to the preparation of the magnesium fluoride coating.

[0050] In the present invention, the temperature of the replacement reaction is preferably 20-40°C, more preferably 25-35°C; the time of the replacement reaction is preferably 45min-6h, more preferably 45min-1h. The present invention limits the temperature and time of the replacement reaction to the above ranges to improve the degree of the replacement reaction.

[0051] After the replacement reaction is completed, the present invention preferably separates the product obtained by the replacement reaction from the solution to obtain a magnesium substrate with a magnesium fluoride coating.

[0052] The present invention has no particular limitation on the operation of separating the product obtained by the replacement reaction from the solution, and any operation well known to those skilled in the art may be used.

[0053] After obtaining the magnesium substrate with the magnesium fluoride coating, the present invention mixes the magnesium substrate with the magnesium fluoride coating, a calcium nitrate solution and an ammonium dihydrogen phosphate solution to perform a precipitation reaction to obtain the magnesium substrate with the fluorinated hydroxyapatite coating.

[0054] In the present invention, the concentration of the calcium nitrate solution is preferably 0.04-0.1 mol / L, more preferably 0.04-0.05 mol / L; the concentration of the diammonium phosphate solution is preferably 0.025-0.06 mol / L, more preferably 0.025-0.03 mol / L; the molar ratio of calcium in the calcium nitrate solution to phosphorus in the diammonium phosphate solution is preferably (1.1-1.85):1, more preferably (1.2-1.85):1.

[0055] In the present invention, the mixing of the magnesium substrate with the magnesium fluoride coating, the calcium nitrate solution and the ammonium dihydrogen phosphate solution is preferably performed by mixing the magnesium substrate with the magnesium fluoride coating and the calcium nitrate solution, and then slowly adding the ammonium dihydrogen phosphate solution.

[0056] The present invention has no special limitation on the operation of mixing the magnesium substrate with the magnesium fluoride coating and the calcium nitrate solution, and the technical scheme for preparing the mixed material well known to those skilled in the art can be adopted.

[0057] The present invention has no particular limitation on the operation of slowly adding the diammonium phosphate solution, and the operation well known to those skilled in the art can be adopted.

[0058] In the present invention, the temperature of slowly adding the ammonium dihydrogen phosphate solution is preferably 80-95°C, more preferably 85-90°C. The magnesium substrate with the magnesium fluoride coating in the present invention releases Mg at the above temperature. 2+ and F - , F - And Ca 2+ , phosphate ion, OH - The reaction forms fluorinated hydroxyapatite, the structural formula of which is as follows:

[0059] 10Ca 2+ +6PO4 3 -+xF - +(2-x)OH - →Ca 10 (PO4)6F x (OH) 2-x .

[0060] In the present invention, the temperature of the precipitation reaction is preferably 80-95°C, more preferably 85-90°C; the time of the precipitation reaction is preferably 45min-2h, more preferably 1-2h. The present invention limits the temperature and time of the precipitation reaction within the above ranges to improve the degree of the precipitation reaction.

[0061] After the precipitation reaction is completed, the present invention preferably sequentially washes and dries the product obtained by the precipitation reaction to obtain a magnesium substrate with a fluorinated hydroxyapatite coating.

[0062] The present invention has no particular limitation on the cleaning and drying operations, and operations well known to those skilled in the art may be used.

[0063] After obtaining the magnesium substrate with the fluorinated hydroxyapatite coating, the present invention coats a polymer on one surface of the magnesium substrate with the fluorinated hydroxyapatite coating to obtain a magnesium metal film that selectively guides tissue regeneration.

[0064] In the present invention, the coating is preferably ultrasonic spraying; the number of ultrasonic spraying is preferably 5 to 50 times, more preferably 5 to 10 times; the speed of the ultrasonic spraying is preferably 5 to 30 mm / s, more preferably 20 to 30 mm / s; the flow rate of the ultrasonic spraying is preferably 0.15 to 0.5 mL / min, more preferably 0.3 to 0.5 mL / min; the concentration of the polymer solution during the ultrasonic spraying is preferably 0.001 to 0.01 g / L; the solvent of the polymer solution is preferably chloroform or hexafluoroisopropanol.

[0065] After coating, the present invention preferably shapes the coated product to obtain a magnesium metal film that selectively guides tissue regeneration.

[0066] The present invention has no special limitation on the forming operation, and the shape can be adjusted according to actual needs.

[0067] The preparation method provided by the invention has simple process.

[0068] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0069] Example 1

[0070] The magnesium metal film for selectively guiding tissue regeneration is composed of a pure magnesium sheet, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the pure magnesium sheet, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating;

[0071] The thickness of the pure magnesium sheet is 0.15 mm;

[0072] The pure magnesium sheet is provided with a large circular hole with a diameter of 2.0 mm and a small circular hole with a diameter of 0.8 mm;

[0073] The mass content of Mg in the pure magnesium is ≥99.98%;

[0074] The thickness of the magnesium fluoride coating is 3 μm;

[0075] The thickness of the fluorinated hydroxyapatite coating is 1.5 μm;

[0076] The thickness of the polymer coating is 3 μm;

[0077] The material of the polymer coating is PLLA, with a weight average molecular weight of M w is 100000;

[0078] The method for preparing the magnesium metal film for selectively guiding tissue regeneration comprises the following steps:

[0079] (1) The pure magnesium sheet was laser cut under nitrogen protection, then polished, and then washed with ethanol for more than three times, and then dried in a 55°C blast drying oven to obtain a pure magnesium sheet with a bright surface; wherein the laser cutting parameters are: energy 35%, laser frequency 950Hz, laser pulse width 100μs; the polishing liquid is a mixture of phosphoric acid and ethanol, the volume ratio is 4:1, and the polishing temperature is 25°C;

[0080] (2) immersing the pure magnesium sheet with a bright surface obtained in step (1) in a hydrofluoric acid solution with a mass concentration of 12% to carry out a replacement reaction for 6 hours to obtain a pure magnesium sheet with a magnesium fluoride coating;

[0081] (3) immersing the pure magnesium flakes with magnesium fluoride coating obtained in step (2) in a 0.04 mol / L calcium nitrate solution, then heating to 80° C., then adding 0.025 mol / L ammonium dihydrogen phosphate under slow stirring, performing precipitation reaction for 2 h, and then washing and drying to obtain pure magnesium flakes with fluorinated hydroxyapatite coating; wherein the molar ratio of calcium in the calcium nitrate solution to phosphorus in the ammonium dihydrogen phosphate solution is 1.85:1;

[0082] (4) placing the pure magnesium sheet with the fluorinated hydroxyapatite coating obtained in step (3) on a clean and dry platform, and ultrasonically spraying one surface of the pure magnesium sheet with a 0.001 g / L PLLA solution 50 times to obtain a pure magnesium sheet with a polymer coating; wherein the ultrasonic spraying speed is 30 mm / s, the flow rate is 0.5 mL / min, and the solvent of the PLLA solution is hexafluoroisopropanol;

[0083] (5) Place the polymer-coated pure magnesium sheet obtained in step (4) with the polymer-coated side facing upward, and place half of it on the pliers head of a homemade oral guided tissue regeneration membrane shaping forceps, hold the pliers handle tightly until the pliers heads are close together, so that half of it becomes a three-dimensional shape, release the pliers handle, and then place the other half on the pliers head of a homemade oral guided tissue regeneration membrane shaping forceps, hold the pliers handle tightly until the pliers heads are close together, so that the other half of it becomes a three-dimensional shape, release the pliers handle, and obtain a magnesium metal film that selectively guides tissue regeneration.

[0084] The structural schematic diagram of the pure magnesium sheet in Example 1 is as follows Figure 1 shown.

[0085] from Figure 1 The positions of the large and small circular holes of the pure magnesium sheet can be clearly known.

[0086] The stereoscopic image of the homemade oral guided tissue regeneration membrane shaping forceps in Example 1 is as follows Figure 2 As shown in the figure, 1 is the pliers head, 2 is the pliers handle, 3 is the spring, 4 is the fixing screw, and 5 is the nut.

[0087] from Figure 2 The shape of the homemade oral guided tissue regeneration membrane shaping forceps can be clearly known.

[0088] The macroscopic image of the magnesium metal film for selectively guiding tissue regeneration prepared in Example 1 is as follows: Figure 3 shown.

[0089] from Figure 3 The shape of the magnesium metal film that selectively guides tissue regeneration can be clearly known.

[0090] Example 2

[0091] The magnesium metal film for selectively guiding tissue regeneration is composed of a magnesium-zinc alloy sheet, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the magnesium-zinc alloy sheet, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating;

[0092] The thickness of the magnesium-zinc alloy sheet is 0.5 mm;

[0093] The magnesium-zinc alloy sheet is provided with a large circular hole with a diameter of 3.0 mm and a small circular hole with a diameter of 2.0 mm;

[0094] The mass content of zinc in the magnesium-zinc alloy is 6%;

[0095] The mass content of magnesium in the magnesium-zinc alloy is ≥ 93.5%;

[0096] The thickness of the magnesium fluoride coating is 4 μm;

[0097] The thickness of the fluorinated hydroxyapatite coating is 2.5 μm;

[0098] The thickness of the polymer coating is 50 μm;

[0099] The material of the polymer coating is PPDO, with a weight average molecular weight of M w is 300000;

[0100] The method for preparing the magnesium metal film for selectively guiding tissue regeneration comprises the following steps:

[0101] (1) The magnesium-zinc alloy sheet is first laser cut under argon protection, then polished, then cleaned with ethanol for more than three times, and then dried in a blast drying oven at 80°C to obtain a magnesium-zinc alloy sheet with a bright surface; wherein the laser cutting parameters are: energy 35%, laser frequency 950Hz, laser pulse width 100μs; the polishing liquid is a mixture of phosphoric acid and ethylene glycol, the volume ratio is 1:4, and the polishing temperature is 60°C;

[0102] (2) immersing the bright-surfaced magnesium-zinc alloy sheet obtained in step (1) in a hydrofluoric acid solution having a mass concentration of 40% to carry out a replacement reaction for 45 minutes to obtain a magnesium-zinc alloy sheet having a magnesium fluoride coating;

[0103] (3) immersing the magnesium-zinc alloy sheet with a magnesium fluoride coating obtained in step (2) in a 0.1 mol / L calcium nitrate solution, then heating to 95° C., then adding 0.06 mol / L ammonium dihydrogen phosphate under slow stirring, performing a precipitation reaction for 45 minutes, and then washing and drying to obtain a magnesium-zinc alloy sheet with a fluorinated hydroxyapatite coating; wherein the molar ratio of calcium in the calcium nitrate solution to phosphorus in the ammonium dihydrogen phosphate solution is 1.1:1;

[0104] (4) placing the magnesium-zinc alloy sheet with the fluorinated hydroxyapatite coating obtained in step (3) on a clean and dry platform, and ultrasonically spraying one surface of the magnesium-zinc alloy sheet with a 0.01 g / L PPDO solution for 5 times to obtain a magnesium-zinc alloy sheet with a polymer coating; wherein the ultrasonic spraying speed is 5 mm / s, the flow rate is 0.15 mL / min, and the solvent of the PPDO solution is chloroform;

[0105] (5) Place the polymer-coated magnesium-zinc alloy sheet obtained in step (4) with the polymer-coated side facing upward, and place half of it on the pliers head of a homemade oral guided tissue regeneration membrane shaping forceps, hold the pliers handle tightly until the pliers heads are close together, so that half of it becomes a three-dimensional shape, release the pliers handle, and then place the other half on the pliers head of a homemade oral guided tissue regeneration membrane shaping forceps, hold the pliers handle tightly until the pliers heads are close together, so that the other half of it becomes a three-dimensional shape, release the pliers handle, and obtain a magnesium metal film that selectively guides tissue regeneration.

[0106] The fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration prepared in Examples 1 and 2 was characterized by SEM, and the results were as follows: Figure 4 and 5 As shown, Figure 4 This is a SEM image of the fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration prepared in Example 1; Figure 5 This is a SEM image of the fluorinated hydroxyapatite coating in the magnesium metal film for selectively guiding tissue regeneration prepared in Example 2.

[0107] from Figure 4 and 5 It can be seen that the surface of the fluorinated hydroxyapatite coating is relatively rough, which is conducive to cell adhesion and promotes tissue regeneration. The crystal size of the fluorinated hydroxyapatite coating in Example 2 is larger than that in Example 1.

[0108] Comparative Example 1

[0109] The same preparation method as steps (1) and (5) in Example 1 was used, that is, only pure magnesium flakes with a three-dimensional shape and a bright surface were prepared without modification.

[0110] The macroscopic image of the pure magnesium sheet with a three-dimensional shape and bright surface prepared in Comparative Example 1 is as follows: Figure 6 shown.

[0111] Comparative Example 2

[0112] The same preparation method as steps (1) to (3) and (5) in Example 1 is used to prepare pure magnesium sheets having a three-dimensional fluorinated hydroxyapatite coating.

[0113] Comparative Example 3

[0114] The same preparation method as steps (1) and (5) in Example 2 was used to prepare only a magnesium-zinc alloy sheet with a three-dimensional shape and a bright surface without modification.

[0115] In vitro degradation experiment:

[0116] The magnesium metal films for selectively guiding tissue regeneration prepared in Examples 1-2 and Comparative Examples 1-3 were respectively placed in 200 mL PBS buffer (pH 7.40) at 37° C. for three days, and the corresponding pH changes were recorded. The results are shown in Table 1.

[0117] Table 1 pH changes of PBS

[0118]

[0119] As can be seen from Table 1, the pH value change of the PBS solution corresponding to the magnesium metal membrane for selectively guiding tissue regeneration prepared in Examples 1 to 2 is significantly smaller than that in Comparative Examples 1 to 3, indicating that the degradation rate of the membrane modified with fluorinated hydroxyapatite is slower than that of the unmodified membrane, and the degradation rate of the membrane modified with a polymer coating on the basis of the fluorinated hydroxyapatite coating is even slower.

[0120] It can be seen from the above embodiments that the magnesium metal film for selectively guiding tissue regeneration provided by the present invention can significantly slow down the degradation rate of magnesium metal.

[0121] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A magnesium metal film for selectively guiding tissue regeneration, comprising a magnesium substrate, a magnesium fluoride coating and a fluorinated hydroxyapatite coating sequentially coated on the surface of the magnesium substrate, and a polymer coating coated on one side of the fluorinated hydroxyapatite coating.

2. The magnesium metal film according to claim 1, It is characterized in that The thickness of the magnesium substrate is 0.15-0.5 mm.

3. The magnesium metal film according to claim 1, It is characterized in that The thickness of the magnesium fluoride coating is 3-4 μm.

4. The magnesium metal film according to claim 1, It is characterized in that The thickness of the fluorinated hydroxyapatite coating is 1.5-2.5 μm.

5. The magnesium metal film according to claim 1, It is characterized in that The thickness of the polymer coating is 3-50 μm.

6. The magnesium metal film according to claim 1 or 5, It is characterized in that The material of the polymer coating is at least one of PLLA, PDO and PPDO.

7. The method for preparing the magnesium metal film for selectively guiding tissue regeneration according to any one of claims 1 to 6, The following steps are involved: (1) mixing a magnesium substrate with a hydrofluoric acid solution to perform a replacement reaction to obtain a magnesium substrate having a magnesium fluoride coating; (2) mixing the magnesium substrate with the magnesium fluoride coating obtained in step (1), a calcium nitrate solution and an ammonium dihydrogen phosphate solution, and performing a precipitation reaction to obtain a magnesium substrate with a fluorinated hydroxyapatite coating; (3) coating a polymer on one surface of the magnesium substrate having the fluorinated hydroxyapatite coating obtained in step (2) to obtain a magnesium metal film that selectively guides tissue regeneration.

8. The preparation method according to claim 7, It is characterized in that The temperature of the replacement reaction in step (1) is 20-40° C., and the time of the replacement reaction is 45 min-6 h.

9. The preparation method according to claim 7, It is characterized in that In the step (2), the molar ratio of calcium in the calcium nitrate solution to phosphorus in the diammonium phosphate solution is (1.1-1.85):1; the temperature of the precipitation reaction in the step (2) is 80-95° C., and the time of the precipitation reaction is 45 min-2 h.

10. The preparation method according to claim 7, It is characterized in that The coating in step (3) is ultrasonic spraying; the number of ultrasonic spraying is 5 to 50 times, the speed of ultrasonic spraying is 5 to 30 mm / s, and the flow rate of ultrasonic spraying is 0.15 to 0.5 mL / min.

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