CN111035803B - Titanium implant material with anti-infection and osseointegration promoting functions and preparation method thereof - Google Patents
Titanium implant material with anti-infection and osseointegration promoting functions and preparation method thereof Download PDFInfo
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- CN111035803B CN111035803B CN201911080306.1A CN201911080306A CN111035803B CN 111035803 B CN111035803 B CN 111035803B CN 201911080306 A CN201911080306 A CN 201911080306A CN 111035803 B CN111035803 B CN 111035803B
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- hyperbranched polylysine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/06—Titanium or titanium alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The invention relates to a titanium implant material with anti-infection and bone union promoting functions and a preparation method thereof. The invention prepares hyperbranched polylysine (HBPL) by a thermal initiation one-pot method, and covalently grafts HBPL to a titanium sheet by utilizing a silane coupling agent gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane (GPTMS). The hyperbranched polylysine fixed on the surface of the titanium sheet has very good bactericidal effect on gram-positive staphylococcus aureus and gram-negative escherichia coli. Meanwhile, compared with pure titanium, the material can promote the adhesion, proliferation and differentiation of osteoblasts and has no cytotoxicity. The invention has simple process flow and lower production cost, has the functions of resisting infection and promoting osseointegration on the basis of good safety, innovatively applies the hyperbranched polylysine to the field of implants, has important significance in the aspect of titanium implant modification and has good application prospect.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a hyperbranched polylysine modified titanium implant material with antibacterial and osseointegration promoting effects and a preparation method thereof.
Background
Titanium and titanium alloy implant materials are widely used in orthopedics and dental surgery such as dental implantation and bone repair due to good biocompatibility and excellent biomechanical property, and have good application prospect. Infection and loosening are the most important causes of implant implantation failure. However, since titanium itself does not have the function of resisting infection, and after the titanium material body is implanted into the body, the titanium material body is combined with the bone in a mechanical integration manner, inflammation and loosening are easily caused, and finally, the implantation fails. In order to solve the problem, the research and development of titanium implant materials with antibacterial and osseointegration promoting functions become important contents in the field of biomedical materials.
Current anti-infective implant materials often ignore the problem of poor osseointegration, while materials that promote osseointegration ignore the problem of anti-infection. For example, preloaded antibiotics, silver, zinc and their corresponding oxides, and Nitric Oxide (NO) have all been shown to kill bacteria, but the disadvantages are also not negligible. High doses of metal ions may be toxic and inhibit osteoblast activity, thereby affecting bone union. Furthermore, bacteria are susceptible to antibiotic resistance, and early burst release of antimicrobial agents is also a concern. Therefore, the ideal titanium implant material should have at least the functions of anti-bacterial and promoting osseointegration. For example, chinese patent document publication nos.: CN107261202A discloses a method for preparing a titanium metal orthopedic implant surface antibacterial biological composite coating, which comprises forming a layer of titanium dioxide nanotube on the titanium surface by anodic oxidation, depositing hydroxyapatite on the nanotube titanium substrate by deposition technique, and forming hydroxyapatite/antibiotic composite coating on the nanotube surface by gradually dropping. The coating not only has good biological activity, but also has good antibacterial effect when releasing antibiotics. However, the release of the antibacterial agent is difficult to control, and how to adjust the ratio of the antibacterial agent and the bone substance to achieve a best effect remains a problem to be solved.
The epsilon-polylysine is a natural preservative, has the characteristics of broad-spectrum antibiosis and good stability, has already entered the commercial market in Japan, and has good application prospect in food. Hyperbranched polylysine is a highly branched structure, and a large number of terminal residues are common in the research of gene vectors, but the research of using hyperbranched polylysine as an antibacterial agent and enhancing the biological activity of implants is rare.
Disclosure of Invention
The invention aims to provide a titanium implant material with antibacterial and osseointegration promoting functions and a preparation method thereof. The titanium implant material prepared by the method has a stable antibacterial effect, can promote osseointegration of the material, has good biosafety, and has important significance in the field of titanium implant modification.
The preparation method of the titanium implant material comprises the following steps:
1) carrying out alkali heat treatment to enable the clean titanium surface to be provided with active hydroxyl;
2) treating with a silane coupling agent GPTMS to obtain a silane coupling agent modified titanium surface, wherein the tail end of the silane coupling agent modified titanium surface is provided with an epoxy group;
3) soaking the material modified by the silane coupling agent in a hyperbranched polylysine solution for reaction, and covalently grafting the hyperbranched polylysine to the surface of the titanium through the reaction of an epoxy group and an amino group. The hyperbranched polylysine is prepared by adopting a thermal initiation one-pot method, and comprises the following steps: adding potassium hydroxide to neutralize lysine salt as raw material; heating to 150 deg.c to initiate lysine polymerization to obtain reddish brown melt, dialysis, freezing and drying to obtain the hyperbranched polylysine.
In the step 1), NaOH solution is used for the alkali heat treatment, the concentration is 5-10mol/L, the heating temperature is 80 ℃, and the time is 0.5-3 h.
In the step 2), the silane coupling agent is dissolved in a solvent system of 95% methanol and 5% water (volume percentage), the mass fraction of the silane coupling agent is 5-20%, the silane coupling agent is added into the solvent, then the mixture is kept stand for 10min-1h at room temperature, and then the titanium sheet subjected to alkali heat treatment is immersed in the mixture, and the reaction time is 10 min. After the reaction is finished, the solution is discarded, and the material is placed in a vacuum oven at 110 ℃ for vacuum baking for 2-5 h.
The hyperbranched polylysine in the step 3) is dissolved in water, the concentration is 3-10mg/mL, the reaction temperature is 60 ℃, and the reaction time is 3-8 h.
In the method for synthesizing the hyperbranched polylysine in the step 3), the molar ratio of the lysine hydrochloride to the potassium hydroxide is 1:1, and the reaction is carried out for 4-5h at 40 ℃; the lysine polymerization is carried out under the protection of nitrogen and under the stirring condition, and the reaction time is 2-3 d.
Preferably, the hyperbranched polylysine is prepared by a one-pot method of thermal initiation. Specifically, the method comprises the following steps: 1) dissolving 27.45g of lysine hydrochloride in 50mL of water, stirring and dissolving at 40 ℃, dissolving 8.4g of KOH in 30mL of water (namely the molar ratio of the lysine hydrochloride to the potassium hydroxide is 1:1), slowly dropwise adding and mixing, and reacting for 4-5h at 40 ℃; 2) heating to 150 ℃, continuously stirring for 2-3 days under the protection of nitrogen, and maintaining the water in the reaction system at proper time until the color of the melt changes from white to yellow and then to reddish brown; 3) stopping heating, adding methanol to completely dissolve the melt, replacing the solvent with water, dialyzing for 3-5d, freezing, and drying.
The invention has the advantages that:
1) the hyperbranched polylysine is fixed on the titanium plate by a covalent grafting method and a silane coupling agent. The method has the advantages of high reactivity of amino and epoxy groups, mild reaction conditions, simple process, high efficiency, suitability for titanium materials with any shape and good repeatability.
2) The hyperbranched polylysine is innovatively applied to the field of implant materials, and is found to have a good antibacterial effect, and the hyperbranched polylysine has good biological safety as polyamino acid. Meanwhile, in vitro cell experiments also prove that the antibacterial agent has good promotion effect on the behaviors of adhesion, proliferation and the like of osteoblasts, which is different from the prior action that a plurality of antibacterial agents inhibit the activity of osteoblasts, provides a new method for constructing the titanium implant material for resisting infection and promoting bone union, and has wide application prospect in the field of medical biomaterials.
Drawings
Ti-OH represents that titanium is treated by alkali, Ti-GPTMS represents that titanium is treated by alkali and then treated by a silane coupling agent, and Ti-HBPL represents that hyperbranched polylysine is grafted finally. Ti-HBPL-7d indicates that the material was soaked in PBS solution for 7 d.
FIG. 1 is SEM surface morphology observation of different modified surfaces, wherein a is a Ti group, b is a Ti-OH group, c is a Ti-GPTMS group, and d is a Ti-HBPL group.
FIG. 2 shows the results of X-ray photoelectron spectroscopy of various modified surfaces.
FIG. 3 shows the result of 6h of live/dead fluorescent staining of Staphylococcus aureus on different titanium surfaces.
FIG. 4 shows the results of live/dead fluorescent staining of E.coli on different titanium surfaces for 6 h.
FIG. 5 shows the morphology of Staphylococcus aureus in SEM after 6h incubation on different titanium surfaces.
FIG. 6 shows the results of counting the number of viable bacteria and calculating the antibacterial rate by plate counting method after Staphylococcus aureus is cultured on different titanium surfaces for 6 h.
FIG. 7 shows the results of cell activity and proliferation of mouse preosteoblasts cultured on different modified titanium surfaces for 1 day, 3 days and 5 days.
FIG. 8 shows the cell adhesion and spreading of mouse preosteoblasts after culturing on different modified titanium surfaces for 1 day, 3 days and 5 days.
FIG. 9 shows alkaline phosphatase activity of mouse preosteoblasts cultured for 7 days and 14 days after osteogenic induction on the surface of different modified titanium.
Detailed Description
Specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
Example 1
The titanium implant antibacterial and osseointegration promoting functional surface construction comprises the following steps:
1) and (3) synthesis of hyperbranched polylysine: firstly, slowly dripping a KOH solution into a lysine hydrochloride solution, wherein the molar ratio of lysine hydrochloride to KOH is 1:1, and reacting for 4-5h at 40 ℃; secondly, heating to 150 ℃, introducing nitrogen for protection, continuously stirring for 2-3d, maintaining the moisture in the reaction system in due time, and gradually changing the melt from white to yellow and then to reddish brown; and finally, stopping heating, adding methanol to dissolve the melt, converting the solvent into water, dialyzing for 3-5d, freezing and drying to obtain the product.
2) Alkali heat treatment of the titanium surface: ultrasonically cleaning pure titanium in acetone, absolute ethyl alcohol and ultrapure water for 10min respectively, then immersing the pure titanium into a 10mol/L sodium hydroxide solution, reacting for 1h at 80 ℃, taking out the pure titanium, ultrasonically cleaning for 3 times, and drying for later use.
3) Treating a titanium surface with a silane coupling agent: preparing a solvent system of 95% methanol and 5% water, adding a silane coupling agent KH-560 to prepare a solution with the mass fraction of 10%, and standing for 30 min. Immersing the titanium sheet subjected to alkali heat treatment and drying in the solution, taking out after 10min, baking in a baking oven at 110 ℃ for 3h under vacuum condition, taking out, ultrasonically cleaning for 3 times by using methanol, ultrasonically cleaning for 10min by using ultrapure water, and drying for later use.
4) Fixing hyperbranched polylysine on the surface of titanium: preparing an aqueous solution of hyperbranched polylysine with the mass fraction of 5mg/mL, immersing a titanium sheet treated by a surface silane coupling agent into the aqueous solution, reacting the titanium sheet at 60 ℃ for 5 hours, taking out the titanium sheet, ultrasonically cleaning the titanium sheet for 3 times by using ultrapure water, and drying the titanium sheet to obtain the hyperbranched polylysine covalent grafting titanium implant material.
Characterization of physical and chemical properties of the titanium implant material:
1) FIG. 1 is a scanning electron micrograph of different titanium surfaces. Fig. 1a is a picture of pure titanium, and fig. 1b is a picture of the titanium surface after alkali treatment, which clearly shows that many nano-scale holes appear on the titanium surface and the roughness of the surface is increased. The significant differences can be seen in FIG. 1c for the silane coupling agent treated surface and in FIG. 1d for the grafted hyperbranched polylysine.
2) And (3) characterization of titanium surface covalent immobilization hyperbranched polylysine. FIG. 2 is a XPS test of titanium sheets treated differently, which reflects the elemental composition change and covalent bond change of the materials treated differently. The content of Si2p element in the spectrogram after silanization is increased, and the content of spectrogram N1s after grafting the hyperbranched polylysine is obviously increased, which indicates that the grafting process is successfully carried out, and the hyperbranched polylysine is successfully grafted to the titanium surface. And compared with the content of the N element before and after the PBS soaking, the content of the N element is not obviously reduced, which indicates that the coating is more stable.
3) Antibacterial performance test of hyperbranched polylysine modified titanium implant material
Staphylococcus aureus and Escherichia coli were used in this experiment, and other G + and G-bacteria were also suitable for this experiment.
The experiment is divided into four groups of Ti, Ti-OH, Ti-GPTMS and Ti-HBPL. Cutting titanium sheets into sheets of 1mm × 1mm, soaking each group of titanium sheets in 75% ethanol, sterilizing by ultraviolet irradiation for 30min, setting 3 multiple holes in each group, and placing in a 24-hole plate. Respectively diluting Staphylococcus aureus and Escherichia coli with LB medium to 1 × 107CFU/mL, 1mL of bacterial suspension was added per well and incubated at 37 ℃ for 6 h. After the time point, each group of titanium sheets was taken out, and gently rinsed 3 times with PBS to wash off bacteria not adhered to the surfaces of the titanium sheets. The bacteria on the surface of the titanium sheet are stained by a live/dead bacteria staining method, SYTO 9 can enable the live bacteria to emit green fluorescence, and PI (propdium iodide) staining solution can enable the dead bacteria to emit red fluorescence. And dyeing the mixed dye solution for 15min in a dark place, and then, observing the titanium plate under a fluorescence microscope.
FIG. 3 is a photograph showing the fluorescent staining of Staphylococcus aureus cultured on the surface of titanium plate for 6 hours. It is clear that the Ti, Ti-OH and Ti-GPTMS groups all distributed a large number of live bacteria on the surface, while the Ti-HBPL group was almost all dead bacteria. The fluorescent area can be analyzed and counted by using Image J software, and compared with a pure titanium group, the sterilization rate of the Ti-HBPL group reaches more than 99%, and the antibacterial effect is good. FIG. 4 is a photograph of fluorescence staining of Escherichia coli after 6h of culture on the surface of titanium plate, and the Ti-HBPL group exhibited excellent antibacterial effect similar to Staphylococcus aureus.
And (5) observing the bacterial morphology on the surface of the titanium plate by using SEM. The titanium plate was sterilized and placed in a 24-well plate, 1mL of which was added per well at a concentration of 1X 107Culturing bacterial suspension of CFU/ml Staphylococcus aureus at 37 deg.C for 6 hr, taking out titanium plate, slightly rinsing with PBS to remove bacteria not adhered on surface, and polymerizing with 4%Fixing formaldehyde for 30min, washing off residual paraformaldehyde, performing gradient dehydration with 10%, 30%, 50%, 70%, 80%, 90% and anhydrous ethanol, drying, and observing with a scanning electron microscope.
FIG. 5 is SEM photograph of the bacterial morphology of Staphylococcus aureus cultured on different titanium surfaces for 6 h. FIG. 5a is the pure Ti group, FIG. 5b is the Ti-OH group, FIG. 5c is the Ti-GPTMS group, and FIG. 5d is the Ti-HBPL group. The pure titanium group can be seen to be adhered by a large amount of bacteria and form clusters, the Ti-OH group and the Ti-GPTMS group are similar to the pure Ti group, the cocci are piled together on the surface, and the shape state is good. In the Ti-HBPL group, the bacteria are obviously sparsely distributed, a plurality of dead bacteria can be seen, the cell membrane of the bacteria is broken, and the shape is not spherical. Therefore, the titanium sheet with the surface modified with the hyperbranched polylysine can obviously inhibit the growth of bacteria on the surface of the material and kill the bacteria.
Counting the number of viable bacteria by a dilution coating flat plate method and quantitatively calculating the antibacterial rate. The titanium plate was sterilized and placed in a 24-well plate, 1mL of which was added per well at a concentration of 1X 107Culturing a bacterial suspension of CFU/ml staphylococcus aureus at 37 ℃ for 6h, taking out a titanium sheet, slightly rinsing the titanium sheet by PBS to remove bacteria which are not adhered on the surface, ultrasonically treating for 3min to desorb the adhered bacteria, performing gradient dilution by PBS, coating a plate, culturing in an incubator at 37 ℃ for 24h, taking out, and counting the number of bacterial colonies.
FIG. 6 shows the results of plate counting method after culturing Staphylococcus aureus on different titanium surfaces for 6 h. The number of live bacteria adhered to the surfaces of Ti, Ti-OH, Ti-GPTMS and Ti-HBPL after 6 hours is respectively as follows: 355X 103、310×103、205×103And 45X 103Compared with pure titanium, the antibacterial rate of the Ti-HBPL group can reach 87.3 percent.
The experiments fully show that compared with pure titanium, the material with the surface grafted with the hyperbranched polylysine can obviously inhibit the growth of staphylococcus aureus and has good inhibition effect on escherichia coli.
4) Cell compatibility and bone promotion experiment of hyperbranched polylysine modified titanium implant material
Mouse preosteoblasts MC3T3-E1 were used in this experiment, but some other types of cells such as human bone marrow mesenchymal stem cells or osteoblasts are also suitable for this experiment.
Adhesion experiment of cells on the surface of the material. The experiment was divided into four groups: ti, Ti-OH, Ti-GPTMS and Ti-HBPL groups. Sterilizing each group of titanium sheets, placing into 24-pore plate, adding 1mL per pore with density of 1 × 104MC3T3-E1 cells per mL. 37 ℃ and 5% CO2After culturing in a cell culture box for 1 day, 3 days and 5 days respectively under the condition, taking the materials at each time point, rinsing the materials by PBS for 3 times to wash off the cells which are not adhered, dyeing for 5min by FDA dye solution under the condition of keeping out of the sun, washing off the residual dye solution, and observing the titanium plate under a fluorescence microscope. FDA is a cytoplasmic dye that allows living cells to fluoresce green.
FIG. 7 is a photograph of fluorescent FDA staining of MC3T3-E1 cells after 1, 3, and 5 days of culture on different titanium surfaces. From the result of 1 day of culture, the cell adhesion number of the Ti-HBPL group is slightly increased compared with that of the pure Ti group, but the adhesion area is greatly improved compared with that of the pure titanium group, which shows that the titanium surface grafted with the hyperbranched polylysine on the surface is beneficial to the early adhesion and spreading of the cells. The difference between 3d and 5d was not significant due to the excess cell number.
The CCK-8 method is used for testing the activity and proliferation of cells on the surface of a material. As above, the experiment was divided into four groups, and MC3T3-E1 cells in good growth state were collected, and sterilized titanium plates were placed in 24-well plates, to each of which 1X 10 cells were added4Cells, cultured for 1 day, 3 days and 5 days, respectively. After each time point, the medium was discarded, rinsed 3 times with PBS, 950. mu.L of fresh medium and 50. mu.L of CCK-8 solution were added to each well, and incubation continued in the cell incubator for 4 h. Each well absorbs 100 μ L of culture solution, and the absorbance of each well at 450nm is measured by a microplate reader.
The CCK-8 method is a convenient and rapid method for detecting cytotoxicity and proliferation. CCK-8 can be reduced to colored formazan by mitochondrial succinate dehydrogenase in living cells, so that the more living cells, the darker the color, and the higher the OD. FIG. 8 shows the results of CCK-8 assay after culturing MC3T3-E1 cells on different titanium surfaces for 1 day, 3 days, and 5 days. As can be seen from the data in 1d, the activity of the Ti-HBPL group is higher than that of the other three groups, which indicates that the material with the surface grafted with the hyperbranched polylysine has good cell compatibility and no cytotoxicity. Combining the data of 3d and 5d, the activity of the Ti-HBPL group is still maintained at a higher level compared with pure titanium, which indicates that the titanium plate with the surface grafted with the hyperbranched polylysine is beneficial to the proliferation of cells on the surface.
Alkaline phosphatase activity of cells on different titanium surfaces. The experiment was divided into four groups, and the titanium plates were sterilized and placed in a 24-well plate, and well-grown MC3T3-E1 cells were sampled at 1X 104Density of cells/well. After being cultured for 1 day by using a common alpha MEM culture medium, the culture medium is changed into an osteogenic induction culture medium, and the formula of the osteogenic induction culture medium is as follows: to 250ml of α MEM medium were added 10% FBS, 0.1. mu. mol/L dexamethasone, 50. mu. mol/L ascorbic acid and 10. mu. mol/L sodium β -glycerophosphate. Every two days, the solution was changed, and the level of alkaline phosphatase was measured after 7d and 14 d. Lysing cells by using 1% TritonX-100 to obtain a cell lysate, detecting the total protein content in the cell lysate by using a trace BCA protein detection kit according to a standard curve, and obtaining the corresponding ALP activity by using an ALP activity detection kit.
Alkaline phosphatase (ALP) is an important marker for early bone formation, and higher activity of alkaline phosphatase means better mineralization of bone tissue. FIG. 9 shows that 7d and 14d osteogenic induction cultures showed that the Ti-HBPL group had higher ALP activity than the pure titanium group, which indicates that the surface modification of hyperbranched polylysine was beneficial to increase the activity of alkaline phosphatase and to promote early bone formation.
The above embodiments are only intended to illustrate the technical solutions of the present invention, and those skilled in the art can make many changes or additions in form and detail according to the content and the specific embodiments of the present invention, and these changes and additions should also be regarded as the protection scope of the present invention.
Claims (7)
1. A titanium implant material with anti-infection and osseointegration promotion functions is characterized in that a hyperbranched polylysine coating is fixed on the surface of a titanium implant; the hyperbranched polylysine is fixed on the surface of the titanium substrate in a covalent grafting mode.
2. The titanium implant material as claimed in claim 1, wherein the functional epoxy group is introduced to the surface of the titanium substrate, and covalently bonds with the functional amino group of the hyperbranched polylysine.
3. The titanium implant material with anti-infection and osseointegration promoting functions as claimed in claim 1, which is prepared by the following steps:
1) ultrasonically cleaning pure titanium in acetone, absolute ethyl alcohol and ultrapure water respectively, and drying at room temperature;
2) immersing the titanium plate into a sodium hydroxide solution, and carrying out alkali heat treatment to obtain a titanium plate with active hydroxyl on the surface;
3) immersing in a solution containing silane coupling agent gamma- (2, 3-epoxypropoxy) propyl trimethoxy silane, and reacting at room temperature to make the titanium sheet have epoxy groups;
4) immersing the titanium implant material into a hyperbranched polylysine solution to react at 60 ℃ to obtain the titanium implant material with anti-infection and bone union promoting functions; the synthesis method of the hyperbranched polylysine comprises the following steps: (1) KOH is added into lysine hydrochloride according to the molar ratio of 1:1, and the reaction is carried out for 4 to 5 hours at the temperature of 40 ℃; (2) heating to 150 ℃, stirring and reacting for 2-3 days under the protection of nitrogen, maintaining the water in the reaction system at proper time, and gradually changing the color of the melt from white to yellow and then to reddish brown; (3) and dissolving the melt with methanol, converting the solvent into water, dialyzing for 3-5 days, freezing and drying to obtain the hyperbranched polylysine.
4. The titanium implant material as claimed in claim 3, wherein the concentration of the NaOH solution in step 2) is 5-10mol/L, the heating temperature is 80 ℃ and the heating time is 0.5-3 hours.
5. The titanium implant material as claimed in claim 3, wherein the silane coupling agent is 5-20% by mass in the solution containing γ - (2, 3-glycidoxy) propyltrimethoxysilane in step 3), the solvent system is 95% methanol +5% water, the silane coupling agent is added to the solvent, the mixture is allowed to stand at room temperature for 10 minutes to 1 hour, and then the titanium sheet after the alkali heat treatment is immersed therein for 10 minutes; after the reaction is finished, the solution is discarded, and the material is placed in a vacuum oven at 110 ℃ for vacuum baking for 2-5 hours.
6. The titanium implant material as claimed in claim 3, wherein the hyperbranched polylysine is dissolved in the solution of step 4) in water at a concentration of 3-10mg/mL, at a reaction temperature of 60 ℃ for 3-8 hours.
7. Use of the titanium implant material according to any one of claims 1 to 3 for the preparation of dental or orthopaedic implants.
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