A bioactive coating for the surface of a skull-repair titanium mesh and a method for preparing the same

Abstract

The application discloses a kind of biological activity coating of skull repair titanium mesh surface and preparation method thereof, belong to functional coating technical field, the titanium mesh surface is coated with bone integration coating and skin repair coating, bone integration coating is the bioactive glass coating formed by bioactive glass precursor solution, skin repair coating is ion crosslinked natural polysaccharide-based coating, specifically, the bioactive glass coating, the mass ratio of silicon dioxide, diaphosphorus pentoxide, sodium oxide, calcium oxide and boron oxide is 43~23:7:22:23:5~25;Ion crosslinked natural polysaccharide-based coating includes natural polysaccharide, epidermal growth factor and calcium ion, natural polysaccharide includes at least one of chitosan, algal polysaccharide and aloe polysaccharide, the mass ratio of natural polysaccharide and epidermal growth factor is 15~35:0.05-1.2;The titanium mesh implant body with the biological activity coating on the surface not only has bone integration ability, but also can promote skin repair.

Description

Technical Field

[0001] This invention belongs to the field of functional coating technology, specifically relating to a bioactive coating for the surface of a titanium mesh for cranial repair and its preparation method. Background Technology

[0002] Skull defects often occur during the treatment of traumatic brain injury, cerebrovascular disease, and brain tumors, necessitating cranioplasty to reshape the defective area. Clinically, artificial materials such as titanium mesh and polyetheretherketone (PEEK) are widely used for skull defect repair, with titanium mesh being particularly prevalent due to its relatively low cost. However, due to the inherent bioinertness of titanium mesh and the mismatch in mechanical properties between it and host tissues, patients often experience complications such as postoperative bleeding, tissue infection, and rejection by surrounding tissues after titanium mesh cranioplasty. Reports indicate that the exposure rate and subsequent infection rate of implanted titanium mesh are as high as 13.9%. In particular, rejection can lead to a series of problems, including non-fusion between the titanium mesh and autologous bone (skull, dura mater, etc.), thinning of the scalp, and eventual mesh exposure. Prolonged exposure of the titanium mesh can easily cause intracranial infection. Furthermore, due to recurrence of infection, the titanium mesh implant must eventually be removed to adequately treat the infection and achieve some wound healing. In addition, infection can spread to underlying tissues, leading to epidural abscesses, and in some cases, encephalitis. Surface modification of cranial repair mesh can fundamentally solve a series of problems caused by acute and chronic rejection after surgery.

[0003] Good osseointegration is crucial for the long-term bonding of titanium mesh implants with the skull, dura mater, and other surfaces. To achieve better interfacial integration and simultaneously inhibit scalp thinning, improvements to the surface of titanium mesh implants are urgently needed. While various materials have been shown to promote osseointegration, materials that simultaneously promote both osseointegration and skin repair are relatively rare. Bioglass shows great potential in tissue engineering, such as bone tissue engineering, cartilage tissue engineering, and wound healing, and is currently a research hotspot. It has been proven to have higher bioactivity and better osseointegration than hydroxyapatite.

[0004] Chinese patent document CN110075349A discloses a bioactive glass composite scaffold, which is prepared by mixing 45S5 bioactive glass powder (45wt% SiO2, 24.5wt% Na2O, 24.5wt% CaO and 6wt% P2O5) powder with XLS (lithium magnesium silicate) powder through template replication and high temperature sintering. The composite scaffold has good osteoinductive properties.

[0005] The main drawback of bioactive glass is its brittleness, which further limits its applications. To address this issue, researchers have developed a composite layer by depositing bioactive glass onto a metallic substrate, combining good mechanical properties with high bioactivity. Existing technologies such as enamel, glazing, magnetron sputtering, and pulsed laser deposition have been used to prepare these composite layers.

[0006] Bioengineered materials containing natural ingredients hold promise for solving tissue rejection at the point where the mesh adheres to the scalp, thereby mitigating the risks of scalp thinning and mesh exposure. Summary of the Invention

[0007] This invention provides a bioactive coating for the surface of a titanium mesh implant for cranial repair. The bioactive coating includes a bone integration coating and a skin repair coating, both of which are in direct contact with the surface of the titanium mesh. It not only has bone integration capabilities but also promotes skin repair, thus solving problems such as poor interfacial integration between titanium mesh implants and tissues such as the skull and dura mater, as well as slow wound healing leading to secondary infections.

[0008] The specific technical solution adopted is as follows:

[0009] A bioactive coating for the surface of a titanium mesh for cranial repair, wherein the titanium mesh surface is coated with a bone integration coating and a skin repair coating, both of which are in direct contact with the titanium mesh surface. The bone integration coating is a bioglass coating formed by a bioglass precursor solution, and the skin repair coating is an ion-crosslinked natural polysaccharide-based coating.

[0010] When a titanium mesh implant with the bioactive coating of the present invention is used for cranioplasty, the titanium mesh implant is coated with an osteointegration coating on the side of the skull and the side of the dura mater, and a skin repair coating on the side of the titanium mesh implant near the scalp, thereby simultaneously achieving the osteointegration and skin repair functions of the titanium mesh implant.

[0011] Preferably, in the bio-glass coating, the mass ratio of silicon dioxide, phosphorus pentoxide, sodium oxide, calcium oxide and boron oxide is 43-23:7:22:23:5-25.

[0012] More preferably, in the bio-glass coating, the mass fractions of silicon dioxide, phosphorus pentoxide, sodium oxide, calcium oxide and boron oxide are 43-23%, 7%, 22%, 23% and 5-25%, respectively.

[0013] Borosilicate bioglass is a type of bioglass made by replacing some silicon dioxide with boron oxide. Its properties largely fall between those of silicate and borate bioglasses, such as degradation rate, thermoforming ability, and crystallization tendency. Borosilicate bioglass possesses dual functions of bone integration and skin regeneration; the release of boron ions can further stimulate the regeneration of scalp fibroblasts.

[0014] The ion-crosslinked natural polysaccharide-based coating contains natural polysaccharides, epidermal growth factor, and calcium ions; the natural polysaccharides include at least one of chitosan, seaweed polysaccharides, and aloe polysaccharides, and the mass ratio of natural polysaccharides to epidermal growth factor is 15-35:0.05-1.2.

[0015] More preferably, the carrier is polydimethylsiloxane.

[0016] Natural components such as seaweed polysaccharides, aloe polysaccharides, and chitosan all promote the synthesis of extracellular matrix, thereby achieving wound repair. The cross-linking of calcium ions gives the skin repair coating a porous structure, facilitating cell adhesion and proliferation. Epidermal growth factor (EGF), also known as oligopeptide-1, is an active substance in the human body that can stimulate the division and proliferation of skin cells both in vitro and in vivo, promote cell differentiation, rapidly repair damaged skin, promote the healing of surgical wounds and skin regeneration, and restart damaged and aging skin cells.

[0017] This invention utilizes a skin repair coating primarily composed of natural ingredients such as chitosan, seaweed polysaccharides, aloe polysaccharides, and epidermal growth factor (EGF) applied to the surface of a titanium mesh to stimulate skin healing and slow down scalp thinning. Furthermore, leveraging the similar thermal expansion properties of bioglass to titanium alloys and the high bioactivity of bioglass, a bone integration coating is prepared by spraying a plasma precursor liquid onto the titanium mesh surface. This not only improves the mechanical properties of the bioglass but also simultaneously provides bone integration and skin repair functions. This addresses the problems of unsatisfactory implant appearance and secondary infections caused by slow wound healing in existing technologies.

[0018] Preferably, the thickness of the osteointegration coating is 10–20 micrometers, and the thickness of the skin repair coating is 5–10 micrometers.

[0019] This invention also provides a method for preparing the bioactive coating on the surface of the titanium mesh for cranial repair, specifically including the following steps:

[0020] (1) The surface of the titanium mesh is roughened by sandblasting, then cleaned, sterilized and dried;

[0021] (2) Bone integration coating and skin repair coating were prepared on the surface of titanium mesh by plasma liquid spraying and atomization spraying, respectively.

[0022] When preparing bone integration coatings using plasma liquid spraying, the spraying raw material is a bioglass precursor solution, which is prepared using silicon, phosphorus, sodium, calcium, and boron sources as raw materials.

[0023] When preparing skin repair coatings using the atomized spraying method, the spraying raw material is a mixed gel containing a carrier, natural polysaccharides, epidermal growth factors, calcium ions, and a curing agent.

[0024] By using bioglass precursor solutions instead of suspensions or powdered raw materials to prepare coatings on titanium mesh surfaces, coatings with unique properties have been obtained, and thinner coatings can be easily produced. Using precursor solutions to prepare osseointegration coatings has two significant advantages: firstly, it allows for the preparation of more uniform, thinner, and dimensionally controllable nanostructured coatings; secondly, powder or suspension spraying raw materials can only utilize pure substances, resulting in higher costs and the introduction of contaminants. In contrast, bioglass precursor solutions, applied via plasma liquid spraying, can form a uniform, one-piece bioglass thin layer on the titanium mesh surface. This is an effective method for solving the interfacial fusion problem between titanium mesh implants and the skull, dura mater, etc.

[0025] Compared with other deposition technologies, plasma spraying has a high deposition rate, better control over substrate degradation, and easier control over coating morphology, thickness and structure. It is also easier to produce dense coatings for implantable devices.

[0026] Step (1) specifically includes the following steps: first, use a sandblasting machine to sandblast the surface of the titanium mesh, then use anhydrous ethanol for ultrasonic cleaning for 15 minutes, then use an autoclave for sterilization, and finally dry.

[0027] Preferably, the preparation method of the bioglass precursor solution includes: firstly, dissolving an appropriate amount of tetraethyl orthosilicate (TEOS) in deionized water and stirring until clear; adding a necessary amount of nitric acid as a catalyst to accelerate hydrolysis; then sequentially adding ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate, and boric acid; stirring for 0.5 h after each addition to obtain a mixed solution; then continuing to stir for 1 h; and allowing to stand overnight at room temperature to obtain the bioglass precursor solution.

[0028] Further preferred, the concentration of nitric acid is 0.2M. If the concentration is too high, the viscosity of the precursor solution will increase significantly, the precursor solution will gel severely, forming a dense gel, which will clog the syringe.

[0029] The process parameters for plasma liquid coating are as follows: the bioglass precursor solution is delivered by a peristaltic pump; the working gases include argon and hydrogen; the current intensity is 500-800A; the spraying distance is 60-90mm; the number of sprays is 5-20; and the spraying speed is 600-1000mm / s.

[0030] The method for preparing the hybrid gel includes: adding natural polysaccharides to polydimethylsiloxane prepolymer, then adding epidermal growth factor (EGF), followed by adding calcium ions for crosslinking, and finally adding a curing agent to obtain the hybrid gel.

[0031] Natural polysaccharides have skin repair functions, and epidermal growth factor can stimulate the division and proliferation of skin cells, rapidly repair damaged skin, promote the healing of surgical wounds and skin regeneration, and solve the problem of tissue rejection between titanium mesh implants and human tissues, thereby reducing the risk of scalp thinning and titanium mesh exposure.

[0032] Preferably, the mass ratio of polydimethylsiloxane prepolymer to curing agent is 4 to 20:1.

[0033] The process parameters for the atomization spraying method are as follows: the mixed gel is sprayed onto the surface of the titanium mesh through an atomizing nozzle; the mixed gel is atomized using high-purity argon gas of 0.6 to 1.8 MPa, the diameter of the atomizing nozzle is 0.8 mm, the spraying distance is 30 to 50 mm, and the number of spraying times is 2 to 6.

[0034] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0035] (1) The titanium mesh implant (titanium mesh with the bioactive coating on the surface) prepared by the present invention not only has osseointegration capability, but also promotes skin repair; the skin repair coating, which is mainly composed of natural ingredients, can stimulate skin healing and slow down scalp thinning, reduce tissue rejection, and prevent mesh exposure; bioglass has thermal expansion properties similar to titanium alloy and high bioactivity. The osseointegration coating is prepared by spraying plasma precursor liquid onto the surface of the titanium mesh, which not only improves the mechanical properties of bioglass, but also has osseointegration and skin repair functions at the same time; the skin repair coating and the osseointegration coating work together to prepare a high-performance titanium mesh implant.

[0036] (2) This invention uses a bioglass precursor solution instead of suspension or powder raw materials to prepare a coating on the surface of a titanium mesh, resulting in a coating with unique properties that is easy to produce thinner coatings. Using a precursor solution to prepare a bone integration coating has two significant advantages. On the one hand, it can produce a more uniform, thinner coating with a controllable microstructure of nanostructure. On the other hand, powder or suspension spraying raw materials can only use pure substances, which is costly and can also lead to the introduction of some contaminants. However, the bioglass precursor solution, through plasma liquid spraying, can form a uniform bioglass thin layer on the surface of the titanium mesh in one step.

[0037] (3) Compared with other deposition technologies, plasma liquid deposition technology has a high deposition rate, better control over substrate degradation, and easier control over coating morphology, thickness and structure, which in turn makes it easier to control the performance of the product coating. In addition, the coating prepared by plasma liquid deposition technology is dense and suitable for large-scale production, with good application prospects and economic benefits. Attached Figure Description

[0038] Figure 1 This is a schematic diagram of a titanium mesh with the bioactive coating of the present invention implanted in the human brain.

[0039] Figure 2 This is a surface SEM image of the skin repair coating in Example 1.

[0040] Figure 3 This is a surface SEM image of the osseointegration coating in Example 2.

[0041] Figure 4 This is a cross-sectional SEM image of the bone integration coating in Example 3. Detailed Implementation

[0042] The present invention will be further illustrated below with reference to the embodiments and accompanying drawings. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0043] In this embodiment, the epidermal growth factor was purchased from Shanghai McLean Biochemical Technology Co., Ltd., and the titanium mesh was purchased from Ningbo Cibei Medical Device Co., Ltd.

[0044] Example 1

[0045] (1) The pretreatment process of titanium mesh includes: first, surface sandblasting is performed using a sandblasting machine, then ultrasonic cleaning is performed with anhydrous ethanol for 15 minutes, then sterilization is performed using an autoclave, and finally drying is performed to obtain the pretreated titanium mesh.

[0046] (2) The preparation method of the bioglass precursor solution includes: firstly, dissolving an appropriate amount of tetraethyl orthosilicate (TEOS) in deionized water and stirring until clear. To accelerate hydrolysis, a necessary amount of 0.2M nitric acid can be added as a catalyst. Then, ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate and boric acid are added sequentially (the specific amounts of silicon source, phosphorus source, sodium source, calcium source and boron source added are calculated from the mass ratio of the corresponding oxides in the target product coating). After each addition, the mixture is stirred for 0.5h to obtain a mixed solution. Then, the mixture is stirred for another 1h and left at room temperature overnight to obtain the bioglass precursor solution. The final concentration of the bioglass precursor solution is 4M.

[0047] (3) The preparation method of the mixed gel includes: adding chitosan to polydimethylsiloxane prepolymer, adding an appropriate amount of EGF, adding calcium ions for cross-linking, and finally adding a curing agent to form a mixed gel; wherein, the mass ratio of chitosan to epidermal growth factor is 15:0.05; and the mass ratio of prepolymer to curing agent is 10:1.

[0048] (4) The osteointegration coating and skin repair coating on the surface of titanium mesh were prepared by plasma liquid spraying of bioglass precursor solution and atomized spraying of mixed gel, respectively.

[0049] The process parameters for plasma liquid deposition are as follows: the bioglass precursor solution delivery system uses a peristaltic pump with a flow rate of 40 ml / min; the working gases used include argon and hydrogen, with argon pressure at 0.7 MPa and a flow rate of 20 ml / min; hydrogen pressure at 0.4 MPa and a flow rate of 2.5 ml / min; the current intensity is 500-800 A; the spraying distance is 60 mm; the number of spraying passes is 15; and the spraying speed is 600 mm / s.

[0050] The process parameters for atomized spraying are as follows: the mixed gel is sprayed onto the surface of the titanium mesh through an atomizing nozzle; the mixed gel is atomized using high-purity argon gas of 0.6–1.8 MPa, the atomizing nozzle diameter is 0.8 mm, the spraying distance is 50 mm, the number of sprays is 5, and the mixture is dried at 45°C for 30 min.

[0051] The prepared titanium mesh implant has a 17-micron osseointegration coating and an 8-micron skin repair coating on its surface. Both the osseointegration coating and the skin repair coating are in direct contact with the titanium mesh surface. In the osseointegration coating, the mass fractions of boron oxide, sodium oxide, calcium oxide, silicon dioxide and phosphorus pentoxide are 5%, 22%, 23%, 43% and 7%, respectively. In the skin repair coating, the mass ratio of chitosan and epidermal growth factor is 15:0.05.

[0052] A schematic diagram of implanting a titanium mesh with the bioactive coating of this invention into the human brain is shown below. Figure 1 As shown, the performance of the titanium mesh implant prepared above was tested, and the test results are as follows:

[0053] 1) Observation of the morphology of the osseointegration coating: Au was sprayed onto the surface of the osseointegration coating, and its surface micromorphology was observed using SEM. The results showed that the surface osseointegration coating had good uniformity and good adhesion to the substrate.

[0054] 2) Observation of the structure and morphology of the skin repair coating: Au was sprayed onto the surface of the skin repair coating, and its surface microstructure was observed using a scanning electron microscope. The results are as follows: Figure 2 As shown, the skin repair coating has a porous morphology.

[0055] 3) Bioactivity test of osseointegration coating: After 7 days in simulated body fluid (SBF), a thick (about 50 nm) hydroxyapatite (HA) layer was observed to form on the surface of the osseointegration coating.

[0056] 4) Fibroblast proliferation assay on skin repair coating: The proliferation rate of fibroblasts on the skin repair coating was 50% as determined by the CCK-8 assay kit.

[0057] 5) Skin repair coating angiogenesis test: Immunohistochemical staining with CD31 was used to test the angiogenesis activity of the skin repair coating, and the results showed that a large number of blood vessels were formed.

[0058] Example 2

[0059] (1) The pretreatment process of titanium mesh includes: first, surface sandblasting is performed using a sandblasting machine, then ultrasonic cleaning is performed with anhydrous ethanol for 15 minutes, then sterilization is performed using an autoclave, and finally drying is performed to obtain the pretreated titanium mesh.

[0060] (2) The preparation method of the bioglass precursor solution includes: firstly, dissolving an appropriate amount of tetraethyl orthosilicate (TEOS) in deionized water and stirring until clear; to accelerate hydrolysis, a necessary amount of 0.2M nitric acid can be added as a catalyst; then, ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate and boric acid are added sequentially; after each addition, the mixture is stirred for 0.5h to obtain a mixed solution; then, the mixture is stirred for another 1h and left at room temperature overnight to obtain the bioglass precursor solution; the final concentration of the bioglass precursor solution is 4M.

[0061] (3) The preparation method of the mixed gel includes: adding seaweed polysaccharide to polydimethylsiloxane prepolymer, adding an appropriate amount of EGF, adding calcium ions for cross-linking, and finally adding a curing agent to form a mixed gel; the mass ratio of chitosan to epidermal growth factor is 25:0.625; the mass ratio of prepolymer to curing agent is 10:1;

[0062] (4) The osteointegration coating and skin repair coating on the surface of titanium mesh were prepared by plasma liquid spraying of bioglass precursor solution and atomized spraying of mixed gel, respectively.

[0063] The process parameters for plasma liquid deposition are as follows: the bioglass precursor solution delivery system uses a peristaltic pump with a flow rate of 40 ml / min; the working gases include argon and hydrogen, with argon pressure at 0.7 MPa and a flow rate of 20 ml / min; hydrogen pressure at 0.4 MPa and a flow rate of 2.5 ml / min; the current intensity is 500-800 A; the spraying distance is 70 mm; the number of spraying passes is 15; and the spraying speed is 600 mm / s.

[0064] The process parameters for atomized spraying are as follows: the mixed gel is sprayed onto the surface of the titanium mesh through an atomizing nozzle; the mixed gel is atomized using high-purity argon gas of 0.6–1.8 MPa, the atomizing nozzle diameter is 0.8 mm, the spraying distance is 50 mm, the number of sprays is 5, and the mixture is dried at 45°C for 30 min.

[0065] The prepared titanium mesh implant has a 16-micron osseointegration coating and a 9-micron skin repair coating on its surface. Both the osseointegration coating and the skin repair coating are in direct contact with the titanium mesh surface. In the osseointegration coating, the mass fractions of boron oxide, sodium oxide, calcium oxide, silicon dioxide and phosphorus pentoxide are 15%, 22%, 23%, 33% and 7%, respectively. In the skin repair coating, the mass ratio of seaweed polysaccharide and epidermal growth factor is 25:0.625.

[0066] The performance of the titanium mesh implants prepared above was tested, and the results are as follows:

[0067] 1) Observation of the morphology of the osseointegration coating: Au was sprayed onto the surface of the osseointegration coating, and its surface microstructure was observed using SEM. The results are as follows: Figure 3 As shown, the osseointegration coating has a relatively uniform surface and good adhesion to the substrate.

[0068] 2) Observation of the structure and morphology of the skin repair coating: Au was sprayed on the surface of the skin repair coating and its surface micromorphology was observed using SEM. The surface has a porous morphology, which is conducive to cell adhesion.

[0069] 3) Bioactivity test of osseointegration coating: After 12 days in simulated body fluid (SBF), a thick (about 70 nm) hydroxyapatite (HA) layer was observed to form on the surface of the osseointegration coating.

[0070] 4) Fibroblast proliferation assay on skin repair coating: The proliferation rate of fibroblasts on the skin repair coating was 35% when tested using the CCK-8 kit.

[0071] 5) Skin repair coating angiogenesis test: Immunohistochemical staining with CD31 was used to test the angiogenesis activity of the skin repair coating, and the results showed that there was a lot of angiogenesis.

[0072] Example 3

[0073] (1) The pretreatment process of titanium mesh includes: first, surface sandblasting is performed using a sandblasting machine, then ultrasonic cleaning is performed with anhydrous ethanol for 15 minutes, then sterilization is performed using an autoclave, and finally drying is performed to obtain the pretreated titanium mesh.

[0074] (2) The preparation method of the bioglass precursor solution includes: firstly, dissolving an appropriate amount of tetraethyl orthosilicate (TEOS) in deionized water and stirring until clear; to accelerate hydrolysis, a necessary amount of 0.2M nitric acid can be added as a catalyst; then, ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate and boric acid are added sequentially; after each addition, the mixture is stirred for 0.5h to obtain a mixed solution; then, the mixture is stirred for another 1h and left at room temperature overnight to obtain the bioglass precursor solution; the final concentration of the bioglass precursor solution is 4M.

[0075] (3) The preparation method of the mixed gel includes: adding aloe polysaccharide to polydimethylsiloxane prepolymer, adding an appropriate amount of EGF, adding calcium ions for cross-linking, and finally adding a curing agent to form a mixed gel; the mass ratio of chitosan to epidermal growth factor is 35:1.2; the mass ratio of prepolymer to curing agent is 10:1;

[0076] (4) The osteointegration coating and skin repair coating on the surface of titanium mesh were prepared by plasma liquid spraying of bioglass precursor solution and atomized spraying of mixed gel, respectively.

[0077] The process parameters for plasma liquid deposition are as follows: the bioglass precursor solution delivery system uses a peristaltic pump with a flow rate of 40 ml / min; the working gases used include argon and hydrogen, with argon pressure at 0.7 MPa and a flow rate of 20 ml / min; hydrogen pressure at 0.4 MPa and a flow rate of 2.5 ml / min; the current intensity is 500-800 A; the spraying distance is 80 mm; the number of spraying passes is 15; and the spraying speed is 600 mm / s.

[0078] The process parameters for atomized spraying are as follows: the mixed gel is sprayed onto the surface of the titanium mesh through an atomizing nozzle; the mixed gel is atomized using high-purity argon gas of 0.6–1.8 MPa, the atomizing nozzle diameter is 0.8 mm, the spraying distance is 50 mm, the number of sprays is 5, and the mixture is dried at 45°C for 30 min.

[0079] The prepared titanium mesh implant has a 19-micron osseointegration coating and an 8-micron skin repair coating on its surface. Both the osseointegration coating and the skin repair coating are in direct contact with the titanium mesh surface. In the osseointegration coating, the mass fractions of boron oxide, sodium oxide, calcium oxide, silicon dioxide, and phosphorus pentoxide are 25%, 22%, 23%, 23%, and 7%, respectively. In the skin repair coating, the mass ratio of aloe polysaccharide to epidermal growth factor is 35:1.2.

[0080] The performance of the titanium mesh implants prepared above was tested, and the results are as follows:

[0081] 1) Observation of the structural morphology of the osseointegration coating: Au was sprayed onto the surface of the osseointegration coating, and its cross-sectional micromorphology was observed using SEM. The results are as follows: Figure 4 As shown, the coating is relatively uniform and dense, with good adhesion.

[0082] 2) Observation of the structure and morphology of the skin repair coating: Au was sprayed on the surface of the skin repair coating and its surface micromorphology was observed using SEM. The surface has a porous morphology, which is conducive to cell adhesion.

[0083] 3) Bioactivity test of osseointegration coating: After the osseointegration coating was placed in simulated body fluid (SBF) for 18 days, a thick (about 100 nm) hydroxyapatite (HA) layer was observed to form on the surface.

[0084] 4) Fibroblast proliferation assay on skin repair coating: The proliferation rate of fibroblasts on the skin repair coating was 50% as determined by the CCK-8 assay kit.

[0085] 5) Skin repair coating angiogenesis test: Immunohistochemical staining with CD31 was used to test the angiogenesis activity of the skin repair coating, and the results showed that a large number of blood vessels were formed.

[0086] Comparative Example 1

[0087] (1) The pretreatment process of titanium mesh includes: first, surface sandblasting is performed using a sandblasting machine, then ultrasonic cleaning is performed with anhydrous ethanol for 15 minutes, then sterilization is performed using an autoclave, and finally drying is performed to obtain the pretreated titanium mesh.

[0088] (2) The preparation method of the bioglass precursor solution includes: firstly, dissolving an appropriate amount of tetraethyl orthosilicate (TEOS) in deionized water and stirring until clear; to accelerate hydrolysis, a necessary amount of 0.2M nitric acid can be added as a catalyst; then, sodium nitrate, calcium nitrate tetrahydrate and boric acid are added sequentially; after each addition, the mixture is stirred for 0.5h to obtain a mixed solution; then, the mixture is stirred for another 1h and left at room temperature overnight to obtain the bioglass precursor solution; the final concentration of the bioglass precursor solution is 4M.

[0089] (3) Prepare a bone integration coating on the surface of titanium mesh by spraying a bioglass precursor solution with plasma liquid;

[0090] The process parameters for plasma liquid deposition are as follows: the bioglass precursor solution delivery system uses a peristaltic pump with a flow rate of 40 ml / min; the working gases used include argon and hydrogen, with argon pressure at 0.7 MPa and a flow rate of 20 ml / min; hydrogen pressure at 0.4 MPa and a flow rate of 2.5 ml / min; the current intensity is 500-800 A; the spraying distance is 90 mm; the number of spraying passes is 15; and the spraying speed is 600 mm / s.

[0091] The prepared titanium mesh implant has a 17-micron osseointegration coating on its surface. In the osseointegration coating, the mass fractions of boron oxide, sodium oxide, calcium oxide, silicon dioxide and phosphorus pentoxide are 25%, 22%, 23%, 23% and 7%, respectively.

[0092] The performance of the titanium mesh implants prepared above was tested, and the results are as follows:

[0093] 1) Observation of the morphology of the osseointegrated coating: Au was sprayed onto the surface of the osseointegrated coating, and its surface micromorphology was observed using SEM. The osseointegrated coating has poor uniformity and can bond with the substrate.

[0094] 2) Bioactivity test of osseointegration coating: After the coating was placed in simulated body fluid (SBF) for 1 month, a hydroxyapatite (HA) layer was observed to form on the surface, and the HA layer was relatively thin (about 27 nm).

[0095] 3) Osteointegration coating fibroblast proliferation assay: The fibroblasts proliferated by 10% using the CCK-8 kit.

[0096] 4) Osteointegration coating angiogenesis test: Immunohistochemical staining with CD31 showed a small amount of angiogenesis.

[0097] The embodiments described above provide a detailed explanation of the technical solutions of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, additions, or similar substitutions made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A bioactive coating on the surface of a titanium mesh for cranial repair, characterized in that, The titanium mesh surface is coated with an osteointegration coating and a skin repair coating. Both the osteointegration coating and the skin repair coating are in direct contact with the titanium mesh surface. The osteointegration coating is a bioglass coating formed by a bioglass precursor solution, and the skin repair coating is an ion-crosslinked natural polysaccharide-based coating. The titanium mesh is coated with an osteointegration coating on the side of the titanium mesh near the skull and the side of the titanium mesh near the dura mater, and with a skin repair coating on the side of the titanium mesh near the scalp. In the bio-glass coating, the mass ratio of silicon dioxide, phosphorus pentoxide, sodium oxide, calcium oxide and boron oxide is 23~43:7:22:23:5~25; The ion-crosslinked natural polysaccharide-based coating contains natural polysaccharides, epidermal growth factor, and calcium ions; the natural polysaccharides include at least one of chitosan, seaweed polysaccharides, and aloe polysaccharides, and the mass ratio of natural polysaccharides to epidermal growth factor is 15~35:0.05~1.

2.

2. The bioactive coating on the surface of the titanium mesh for cranial repair according to claim 1, characterized in that, The thickness of the osteointegration coating is 10-20 micrometers, and the thickness of the skin repair coating is 5-10 micrometers.

3. The method for preparing the bioactive coating on the surface of the titanium mesh for cranioplasty according to claim 1 or 2, characterized in that, Includes the following steps: (1) The surface of the titanium mesh is roughened by sandblasting, then cleaned, sterilized and dried; (2) Bone integration coating and skin repair coating were prepared on the surface of titanium mesh by plasma liquid spraying and atomization spraying, respectively; When preparing bone integration coatings using plasma liquid spraying, the spraying raw material is a bioglass precursor solution, which is prepared using silicon, phosphorus, sodium, calcium, and boron sources as raw materials. When preparing skin repair coatings using the atomized spraying method, the spraying raw material is a mixed gel containing a carrier, natural polysaccharides, epidermal growth factors, calcium ions, and a curing agent.

4. The method for preparing the bioactive coating on the surface of the titanium mesh for cranial repair according to claim 3, characterized in that, The bioglass precursor solution is prepared by the following method: dissolve tetraethyl orthosilicate in deionized water and stir until clear. Then, add ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate and boric acid in sequence and mix well to obtain a mixed solution. Stir the mixed solution thoroughly and let it stand at room temperature overnight to obtain the bioglass precursor solution.

5. The method for preparing the bioactive coating on the surface of the titanium mesh for cranial repair according to claim 4, characterized in that, Ethyl orthosilicate was dissolved in deionized water and stirred until clear. Nitric acid was added as a catalyst to promote hydrolysis. Then, ethyl triphosphate, sodium nitrate, calcium nitrate tetrahydrate and boric acid were added in sequence.

6. The method for preparing the bioactive coating on the surface of the titanium mesh for cranial repair according to claim 3, characterized in that, The process parameters for plasma liquid coating are as follows: the bioglass precursor solution is delivered by a peristaltic pump; the working gases include argon and hydrogen; the current intensity is 500~800 A; the spraying distance is 60~90 mm; the number of sprays is 5~20; and the spraying speed is 600~1000 mm / s.

7. The method for preparing the bioactive coating on the surface of the titanium mesh for skull repair according to claim 3, characterized in that, The method for preparing the hybrid gel includes: adding natural polysaccharides to polydimethylsiloxane prepolymer, then adding epidermal growth factor, followed by adding calcium ion crosslinking, and finally adding a curing agent to obtain the hybrid gel.

8. The method for preparing the bioactive coating on the surface of the titanium mesh for cranial repair according to claim 3, characterized in that, The process parameters for the atomization spraying method are as follows: the mixed gel is sprayed onto the surface of the titanium mesh through an atomizing nozzle; the mixed gel is atomized using high-purity argon gas of 0.6~1.8 MPa, the spraying distance is 30~50 mm, and the number of spraying times is 2~6.

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