CN112535762B

CN112535762B - Preparation method of micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating

Info

Publication number: CN112535762B
Application number: CN202011204469.9A
Authority: CN
Inventors: 周睿; 周颖; 李明; 靳国瑞; 程嘉辉; 憨勇
Original assignee: Xian Jiaotong University
Current assignee: Xian Jiaotong University
Priority date: 2020-11-02
Filing date: 2020-11-02
Publication date: 2021-09-07
Anticipated expiration: 2040-11-02
Also published as: CN112535762A

Abstract

The invention discloses a preparation method of a micro-arc oxidation titanium surface chitosan/sodium alginate composite hydrogel coating, which comprises the steps of dissolving one or more of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt and sodium salt in water to form electrolyte, immersing a titanium sample in the electrolyte by taking a titanium sample as an anode and a stainless steel tank as a cathode for micro-arc oxidation, and forming a micro-arc oxidation coating on the titanium surface; mixing a chitosan aqueous solution and a sodium alginate aqueous solution, adding a photoinitiator, dripping the photoinitiator on a PDMS template provided with a plurality of holes, placing a micro-arc titanium oxide sample on the template, and irradiating the micro-arc titanium oxide sample by ultraviolet light to form a chitosan/sodium alginate composite hydrogel coating on the micro-arc oxidation coating. According to the invention, the micro-arc titanium oxide surface pattern and the highly controllable composite microgel coating are realized by preparing PDMS templates with different apertures and hole depths. Meanwhile, the composite hydrogel has the antibacterial property of chitosan and the biological activity of sodium alginate.

Description

Preparation method of micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating

Technical Field

The invention relates to the technical field of metal surface modification, in particular to a preparation method of a micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating.

Background

Titanium and titanium alloy are used as metal materials with good biocompatibility and have wide application in the field of medical implants. But it has poor binding to bone tissue and the modulus of elasticity is not matched to bone tissue. And its biological inertness limits its development and application. Micro-arc oxidation can form an oxide layer with a micro-porous structure, and the combination of the implant and the bone tissue is improved. The chitosan has good biocompatibility, biodegradability and antibacterial property, is often used as medical dressing and drug sustained-release carrier, but has poor mechanical property. Sodium alginate is a good bioactive material, and the hydrogel has certain strength and good toughness. The composite hydrogel prepared by mixing sodium alginate and chitosan solution can improve the mechanical property of chitosan and endow the gel with more biological functions. Different PDMS templates are used for loading the hydrogel on the micro-arc titanium oxide test sample, so that the loading of the patterned area of the composite hydrogel can be realized, and the antibacterial property and the biological activity of the implant are improved. The prior art can not enhance the combination of the titanium implant and the bone, can not prepare the chitosan hydrogel with controllable mechanical property, and can not realize the controllable regional loading of the gel.

Disclosure of Invention

The invention aims to solve the problems in the prior art and provides a preparation method of a micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating.

In order to achieve the purpose, the invention adopts the following technical scheme:

a preparation method of a micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating comprises the following steps:

1) dissolving one or more of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt and sodium salt in water to form electrolyte, immersing a titanium sample in the electrolyte by taking a titanium sample as an anode and a stainless steel tank as a cathode for micro-arc oxidation, and forming a micro-arc oxidation coating on the surface of the titanium;

2) placing the patterned template in a culture dish, uniformly mixing the prepolymer of PDMS and a curing agent, pouring the mixture into the culture dish, curing, and demolding to obtain a PDMS hydrogel patterned template;

3) mixing a chitosan aqueous solution and a sodium alginate aqueous solution to obtain a mixed solution, adding a photoinitiator into the mixed solution, then dripping the mixed solution on a PDMS template provided with a plurality of holes, then placing a micro-arc titanium oxide sample on the template, irradiating by ultraviolet light, freezing and drying, and forming a chitosan/sodium alginate composite hydrogel coating on the micro-arc oxidation coating.

The further improvement of the invention is that in the step 1), the micro-arc oxidation parameters are as follows: the micro-arc oxidation adopts pulse voltage, the positive voltage is 250-550V, the negative voltage is 0-100V, the micro-arc oxidation pulse frequency is 200-800 Hz, the duty ratio is 6-30%, and the micro-arc oxidation time is 5-15 min.

The further improvement of the invention is that in the step 1), the titanium sample is TA2, TA3, TA4 industrial pure titanium or TC4 titanium alloy; the lithium salt is lithium phosphate, lithium silicate or lithium sulfate, the calcium salt is calcium phosphate, calcium dihydrogen phosphate, calcium silicate or calcium sulfate, the tin salt is stannic silicate, stannous sulfate or stannous pyrophosphate, the magnesium salt is magnesium silicate, magnesium sulfate or magnesium phosphate, the potassium salt is potassium silicate, potassium dihydrogen phosphate or potassium sulfate, and the sodium salt is disodium EDTA, sodium hydroxide, sodium sulfate, trisodium phosphate or sodium silicate.

The further improvement of the method is that in the step 1), the titanium sample is immersed in the electrolyte at 0-40 ℃ for micro-arc oxidation.

The further improvement of the invention is that in the step 1), the concentration of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt or sodium salt in the electrolyte is 5-30 g/L.

In a further development of the invention, in step 2), the curing temperature is 70 to 100 ℃.

In a further improvement of the invention, in step 3), the aqueous chitosan solution is prepared by the following steps: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10, and uniformly stirring to obtain a chitosan aqueous solution; the chitosan concentration in the chitosan aqueous solution is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of the amount of the chitosan substance.

The further improvement of the invention is that in the step 3), the sodium alginate aqueous solution is prepared by the following processes: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10, and stirring to obtain sodium alginate aqueous solution; the concentration of sodium alginate in the sodium alginate aqueous solution is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of the alginic acid substance.

The invention has the further improvement that in the step 3), the mass ratio of the chitosan to the sodium alginate is 1: 10-10: 1; the irradiation time is 1-10 min;

in the step 3), the addition amount of the photoinitiator is 0.05-0.2% of the volume of the mixed solution; the model of the photoinitiator is I2959; the ultraviolet light is realized by irradiating a 100W ultraviolet light lamp, and the ultraviolet intensity is 4800 mu W/cm²。

The invention is further improved in that in the step 3), the aperture is 0.2-2mm, the depth of the hole is 0.2-2mm, and the shape of the hole is square, round, triangular or star-shaped.

Compared with the prior art, the invention has the beneficial effects that:

(1) according to the invention, through micro-arc oxidation treatment, an oxide layer with a micro-porous structure is formed on the surface of titanium, new bone can grow towards the hole, and the bonding strength of the implant and the bone is improved.

(2) According to the invention, the micro-arc titanium oxide surface pattern and the highly controllable composite microgel coating are realized by preparing PDMS templates with different apertures and hole depths.

(3) The chitosan and sodium alginate composite hydrogel prepared by the invention has the advantage of controllable performance, the mechanical property of the gel can be adjusted by controlling the mixing ratio of the two solutions, the brittleness of the chitosan hydrogel is improved by adding the sodium alginate, and the breaking strength of the chitosan can be improved from 2MPa to 6MPa to the maximum. Meanwhile, the composite hydrogel has the antibacterial property of chitosan and the biological activity of sodium alginate. The hydrogel is loaded on the surface or inside the implant, and is expected to be widely applied in the fields of antibacterial dressings and drug controlled release.

Drawings

FIG. 1 is a schematic structural diagram of a titanium sample of the chitosan/sodium alginate loaded composite hydrogel prepared by the invention.

Fig. 2 is a top view of the titanium coupon of fig. 1.

Fig. 3 is a template for preparing a PDMS film.

Fig. 4 is a PDMS template made in accordance with the present invention for controlling the patterned loading of hydrogels. Wherein, (a) is a template with the aperture of 0.2mm and the hole depth of 0.2mm, and (b) is a template with the aperture of 1mm and the hole depth of 0.8 mm.

FIG. 5 shows the surface topography of the micro-arc oxidized coating prepared by the present invention.

FIG. 6 shows the surface morphology of the micro-arc titanium oxide surface composite hydrogel coating prepared by the present invention.

In the figure, 1 is a regionalized microgel-loaded coating, 2 is a micro-arc oxidation coating, and 3 is a titanium sample.

Detailed Description

The present invention will be described in detail with reference to the accompanying drawings.

The invention provides a preparation method of a micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating, which comprises the following steps:

1) micro-arc oxidation treatment: dissolving a compound containing bioactive elements in water to form an electrolyte, immersing a titanium sample in the electrolyte for micro-arc oxidation by taking the titanium sample as an anode and a stainless steel tank as a cathode, and forming a micro-arc oxidation coating on the surface of the titanium;

2) preparing a hydrogel template: placing the patterned template in a culture dish, uniformly mixing a prepolymer of PDMS (polydimethylsiloxane) and a curing agent in a mass ratio of 10:1, pouring the mixture into the culture dish, curing at 70-100 ℃, and demolding to obtain a PDMS hydrogel patterned template;

3) mixing chitosan aqueous solution and sodium alginate aqueous solution to obtain mixed solution, adding photoinitiator into the mixed solution, then dripping the mixed solution on a PDMS template, placing a micro-arc titanium oxide sample on the template, and placing the micro-arc titanium oxide sample on a 100W ultraviolet lamp (ultraviolet intensity of 4800 mu W/cm)²) And (3) irradiating, freezing and drying to form the chitosan/sodium alginate composite hydrogel coating on the micro-arc oxidation coating.

In the step 1), the compound containing bioactive elements is one or more of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt and sodium salt, wherein the lithium salt is lithium phosphate, lithium silicate or lithium sulfate, the calcium salt is calcium phosphate, calcium dihydrogen phosphate, calcium silicate or calcium sulfate, the tin salt is stannic silicate, stannous sulfate or stannous pyrophosphate, the magnesium salt is magnesium silicate, magnesium sulfate or magnesium phosphate, the potassium salt is potassium silicate, potassium dihydrogen phosphate or potassium sulfate, and the sodium salt is disodium EDTA, sodium hydroxide, sodium sulfate, trisodium phosphate or sodium silicate.

In the step 1), the micro-arc oxidation parameters are as follows: the micro-arc oxidation adopts pulse voltage, the positive voltage is 250-550V, the negative voltage is 0-100V, the micro-arc oxidation pulse frequency is 200-800 Hz, the duty ratio is 6-30%, and the micro-arc oxidation time is 5-15 min.

In the step 1), the titanium sample is TA2, TA3, TA4 industrial pure titanium or TC4 titanium alloy.

In the step 1), the titanium sample is immersed in the electrolyte at 0-40 ℃ for micro-arc oxidation.

In the step 1), the concentration of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt or sodium salt is 5-30 g/L.

In the step 2), the curing temperature is 70-100 ℃.

In the step 3), the chitosan aqueous solution is prepared by the following processes: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10 with sodium bicarbonate solution, and uniformly stirring to obtain chitosan aqueous solution; the chitosan concentration in the chitosan aqueous solution is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of the amount of the chitosan substance.

In the step 3), the sodium alginate aqueous solution is prepared by the following steps: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10 with sodium hydroxide solution, and stirring to obtain sodium alginate aqueous solution; the concentration of sodium alginate in the sodium alginate aqueous solution is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of the alginic acid substance.

In the step 3), the mass ratio of the chitosan to the sodium alginate is 1: 10-10: 1; the irradiation time is 1-10 min;

in the step 3), the addition amount of the photoinitiator is 0.05-0.2% of the volume of the mixed solution; the photoinitiator was type I2959.

In the step 3), a plurality of holes are formed in the PDMS template, the aperture is 0.2-2mm, the depth of each hole is 0.2-2mm, and the shape of each hole is square, circular, triangular or star-shaped.

The following are specific examples.

Example 1

1) Micro-arc oxidation treatment: mixing EDTA disodium salt, Ca (H)₂PO₄)₂And NaOH dissolved in water to form electrolyte, wherein the concentration of EDTA disodium in the electrolyte is 15g/L, and the concentration of Ca (H)₂PO₄)₂The concentration of (2) was 12g/L and the concentration of NaOH was 5 g/L. The method comprises the following steps of (1) taking a titanium sample as an anode, taking a stainless steel tank body as a cathode, adding electrolyte into the stainless steel tank body, immersing the titanium sample 3 in the electrolyte at 30 ℃ for micro-arc oxidation, wherein the micro-arc oxidation parameters are as follows: the micro-arc oxidation coating on the titanium surface is obtained by adopting pulse voltage with the positive pressure of 250V and the negative pressure of 80V, the micro-arc oxidation pulse frequency of 400Hz, the duty ratio of 10 percent and the micro-arc oxidation time of 5 min. Among them, titanium sample 3 was TA2 commercially pure titanium.

2) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 10 g/L. Dropwise adding methacrylic anhydride with the mass being 20 times that of the chitosan, adjusting the pH value to 8 by using a sodium bicarbonate solution, fully stirring to obtain a uniform solution, dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

3) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Methacrylic anhydride with the mass 2 times of that of the sodium alginate is added dropwise, the pH value is adjusted to 8 by using a sodium hydroxide solution, and the mixture is fully stirred to obtain a uniform solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

4) Preparing a hydrogel template: placing a square-hole aluminum template with the aperture of 0.5mm and the hole depth of 0.3mm in a culture dish with the pattern facing upwards, uniformly mixing the prepolymer of PDMS and the curing agent in a mass ratio of 10:1, pouring the mixture into the culture dish until the mixture is higher than the template, vacuumizing to remove internal bubbles, placing the mixture in an oven to cure the mixture at high temperature, taking out and demolding to obtain the PDMS template.

5) Preparation of composite hydrogel: mixing a chitosan solution and a sodium alginate solution according to the mass ratio of 1:1 of chitosan to sodium alginate to obtain a mixed solution,and adding a photoinitiator. The solution is evenly mixed and then is smeared on a PDMS template, a sample is placed on the template, and the sample is placed on a 100W ultraviolet lamp (the ultraviolet intensity is 4800 mu W/cm)²) Irradiating and curing for 5 min. Wherein, the addition amount of the photoinitiator is 0.2 percent of the volume of the mixed solution; the photoinitiator was type I2959.

And (3) placing the solidified sample in liquid nitrogen for quick freezing and shaping, and demoulding after freezing and drying to obtain the chitosan/sodium alginate composite hydrogel coating on the surface of the micro-arc titanium oxide.

Fig. 1 is a schematic structural diagram of a micro-arc titanium oxide sample of the chitosan/sodium alginate-loaded composite hydrogel prepared in this embodiment. The lower layer is a titanium sample 3, the upper layer is a micro-arc oxidation coating 2, the uppermost small cylinder is the prepared regionalized loaded microgel 1, and the top view is shown in figure 2, and the gel pattern is controllable. According to the invention, the PDMS templates with different apertures and hole depths are used, so that the micro-arc titanium oxide surface pattern and the highly controllable composite microgel coating are realized.

Fig. 3 and 4 (a) show a PDMS template used in the present embodiment.

The micro-arc oxidation coating obtained by the experiment is observed by a scanning electron microscope, and the result is shown in fig. 5. As can be seen from fig. 5, the coating surface structure is complete, and a porous nano structure is presented. Referring to fig. 6, when observing the microgel coating generated by the micro-arc titanium oxide sample loaded with the chitosan/sodium alginate composite hydrogel, the microgel is circular and has a certain height. The gel is wrinkled, and the edge of the gel spreads toward the substrate and is bonded with the substrate. The breaking strength of the hydrogel was measured to be 4 MPa.

Example 2

1) Micro-arc oxidation treatment: and dissolving lithium phosphate, calcium sulfate and NaOH in water to form electrolyte, wherein the concentration of the lithium phosphate in the electrolyte is 10g/L, the concentration of the calcium sulfate is 15g/L, and the concentration of the NaOH is 5 g/L. The method comprises the following steps of (1) taking a titanium sample as an anode, taking a stainless steel tank body as a cathode, adding electrolyte into the stainless steel tank body, immersing the titanium sample in the electrolyte at 20 ℃ for micro-arc oxidation, wherein the micro-arc oxidation parameters are as follows: the micro-arc oxidation coating on the titanium surface is obtained by adopting pulse voltage with positive voltage of 500V and negative voltage of 80V, the micro-arc oxidation pulse frequency of 500Hz, the duty ratio of 20 percent and the micro-arc oxidation time of 7 min. The titanium sample was TA3 commercial purity titanium.

2) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 15 g/L. Methacrylic anhydride of which the mass is 20 times that of the chitosan is added dropwise, the pH is adjusted to 8 by sodium bicarbonate solution, and the mixture is fully stirred to obtain uniform solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

3) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Dropwise adding methacrylic anhydride with the mass 2 times that of the sodium alginate, adjusting the pH to 8 by using a sodium hydroxide solution, fully stirring to obtain a uniform solution, dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

4) Preparing a hydrogel template: placing a square-hole aluminum template with the aperture of 1mm and the hole depth of 0.5mm in a culture dish with the pattern facing upwards, uniformly mixing a PDMS main agent and a hardening agent in a ratio of 10:1, pouring the mixture into the culture dish until the mixture is higher than the template, vacuumizing to remove internal bubbles, placing the mixture in an oven to cure the mixture at a high temperature, taking out and demolding to obtain the PDMS template.

5) Preparation of composite hydrogel: mixing chitosan and sodium alginate solution at a ratio of 1:1 to obtain a mixed solution, and adding a photoinitiator. The addition of the photoinitiator is 0.1% of the volume of the mixed solution, the solution is evenly mixed and then coated on a PDMS template, a sample is placed on the template, and the sample is cured for 2min under an ultraviolet lamp.

Fig. 4 (b) shows a PDMS template used in this example. The breaking strength of the hydrogel prepared by the process is 3 MPa.

Example 3

1) Micro-arc oxidation treatment: and dissolving stannous pyrophosphate, potassium silicate and NaOH in water to form electrolyte, wherein the concentration of the stannous pyrophosphate in the electrolyte is 20g/L, the concentration of the potassium silicate is 10g/L, and the concentration of the NaOH is 10 g/L. The method comprises the following steps of (1) taking a titanium sample as an anode, taking a stainless steel tank body as a cathode, adding electrolyte into the stainless steel tank body, immersing the titanium sample in the electrolyte at 30 ℃ for micro-arc oxidation, wherein the micro-arc oxidation parameters are as follows: the micro-arc oxidation coating on the titanium surface is obtained by adopting pulse voltage, positive voltage of 550V and negative voltage of 100V, the micro-arc oxidation pulse frequency of 800Hz, the duty ratio of 6 percent and the micro-arc oxidation time of 10 min. The titanium sample was TA4 commercial purity titanium.

3) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Dropwise adding methacrylic anhydride with the mass 5 times that of the sodium alginate, adjusting the pH to 8 by using a sodium hydroxide solution, fully stirring to obtain a uniform solution, dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

4) Preparing a hydrogel template: placing a round hole type aluminum template with the aperture of 0.5mm and the hole depth of 0.3mm in a culture dish with the pattern facing upwards, uniformly mixing a PDMS main agent and a hardening agent in a ratio of 10:1, pouring the mixture into the culture dish until the mixture is higher than the template, vacuumizing to remove internal bubbles, placing the mixture in an oven to cure the mixture at high temperature, taking out and demolding to obtain the PDMS template.

5) Preparation of composite hydrogel: mixing chitosan and sodium alginate solution at a ratio of 1:1 to obtain a mixed solution, and adding a photoinitiator. The addition of the photoinitiator is 0.05% of the volume of the mixed solution, the solution is evenly mixed and then coated on a PDMS template, a sample is placed on the template, and the sample is cured for 6min under an ultraviolet lamp.

And (3) placing the solidified sample in liquid nitrogen for quick freezing and shaping, and demoulding after freezing and drying to obtain the chitosan/sodium alginate composite hydrogel coating on the surface of the micro-arc titanium oxide. The breaking strength of the hydrogel prepared by the process is 3 MPa.

Example 4

1) Micro-arc oxidation treatment: the method comprises the steps of dissolving monopotassium phosphate, lithium sulfate and EDTA disodium in water to form electrolyte, wherein the concentration of monopotassium phosphate in the electrolyte is 15g/L, the concentration of lithium sulfate in the electrolyte is 15g/L, and the concentration of EDTA disodium is 5 g/L. The method comprises the following steps of (1) taking a titanium sample as an anode, taking a stainless steel tank body as a cathode, adding electrolyte into the stainless steel tank body, immersing the titanium sample in the electrolyte at 10 ℃ for micro-arc oxidation, wherein the micro-arc oxidation parameters are as follows: the micro-arc oxidation coating on the titanium surface is obtained by adopting pulse voltage with the positive voltage of 450V and the negative voltage of 100V, the micro-arc oxidation pulse frequency of 400Hz, the duty ratio of 15 percent and the micro-arc oxidation time of 5 min. The titanium sample was TA2 commercial purity titanium.

5) Preparation of composite hydrogel: mixing chitosan and sodium alginate solution at a ratio of 1:2 to obtain a mixed solution, and adding a photoinitiator. The addition of the photoinitiator is 0.2% of the volume of the mixed solution, the solution is evenly mixed and then coated on a PDMS template, a sample is placed on the template, and the sample is cured for 2min under an ultraviolet lamp.

Example 5

1) Micro-arc oxidation treatment: magnesium sulfate, Ca (H)₂PO₄)₂And sodium silicate dissolved in water to form electrolyte with magnesium sulfate concentration of 25g/L and Ca (H)₂PO₄)₂The concentration of (2) is 15g/L, and the concentration of sodium silicate is 15 g/L. The method comprises the following steps of (1) taking a titanium sample as an anode, taking a stainless steel tank body as a cathode, adding electrolyte into the stainless steel tank body, immersing the titanium sample in the electrolyte at 20 ℃ for micro-arc oxidation, wherein the micro-arc oxidation parameters are as follows: the micro-arc oxidation coating on the titanium surface is obtained by adopting pulse voltage with the positive pressure of 350V and the negative pressure of 0V, the micro-arc oxidation pulse frequency of 400Hz, the duty ratio of 15 percent and the micro-arc oxidation time of 12 min. Wherein, the titanium sample is TC4 titanium alloy.

3) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of sodium alginate being 20 g/L. Dropwise adding methacrylic anhydride with the mass 5 times that of the sodium alginate, adjusting the pH to 8 by using a sodium hydroxide solution, fully stirring to obtain a uniform solution, dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

4) Preparing a hydrogel template: placing a triangular hole aluminum template with the aperture of 0.5mm and the hole depth of 0.3mm in a culture dish with the pattern facing upwards, uniformly mixing a PDMS main agent and a hardening agent in a ratio of 10:1, pouring the mixture into the culture dish until the mixture is higher than the template, vacuumizing to remove internal bubbles, placing the mixture in an oven to cure the mixture at a high temperature, taking out and demolding to obtain the PDMS template.

5) Preparation of composite hydrogel: mixing chitosan and sodium alginate solution at a ratio of 1:2 to obtain a mixed solution, and adding a photoinitiator. The addition of the photoinitiator is 0.2% of the volume of the mixed solution, the solution is evenly mixed and then coated on a PDMS template, a sample is placed on the template, and the sample is cured for 3min under an ultraviolet lamp.

And (3) placing the solidified sample in liquid nitrogen for quick freezing and shaping, and demoulding after freezing and drying to obtain the chitosan/sodium alginate composite hydrogel coating on the surface of the micro-arc titanium oxide. The breaking strength of the hydrogel prepared by the process is 6 MPa.

According to the invention, a titanium sheet is placed in a stainless steel tank filled with electrolyte for micro-arc oxidation, a chitosan solution and a sodium alginate solution are modified by methacrylic anhydride and then mixed, a composite hydrogel is prepared by ultraviolet curing, and the hydrogel is further loaded on a micro-arc titanium oxide sample through PDMS templates with different aperture depths and micropore arrangement modes.

According to the invention, the titanium is firstly subjected to micro-arc oxidation to generate a porous oxide layer so as to improve the combination of the porous oxide layer and bone tissues. The chitosan and sodium alginate are prepared into composite hydrogel, and the composite hydrogel is loaded on the surface of the micro-arc titanium oxide through a PDMS template, so that the implant coating is endowed with more biological functions.

The micro-arc oxidation composite hydrogel coating obtained by the invention has the following characteristics: the coating is a composite coating, the inner layer is an oxide layer and is in a micro-porous structure, and the outer layer is a gel layer and is arranged in a patterning mode. The oxide layer improves the bonding of the implant to the bone tissue and the gel layer improves the antibacterial and biological activity of the implant. PDMS templates with different pore diameters and pore depths are used, and micro-arc titanium oxide surface patterns and a highly controllable composite microgel regionalized load coating are realized.

The invention carries out micro-arc oxidation on the titanium sample to generate an oxide layer with a micro-porous structure, so as to improve the combination of the implant and the bone tissue. Modifying chitosan and sodium alginate solution by methacrylic anhydride, mixing, and preparing hydrogel with optimized performance by an ultraviolet curing method. The composite hydrogel has antibacterial property of chitosan and biological activity of sodium alginate, is loaded on the surface or inside the implant, and is expected to be widely applied to the fields of antibacterial dressings and drug controlled release.

According to the invention, the micro-arc titanium oxide surface pattern and the highly controllable composite microgel coating are realized by preparing PDMS templates with different apertures and hole depths. The patterned area load of the hydrogel not only retains the original structure and performance of the micro-arc oxidation coating, but also endows the implant with good antibacterial property and drug controlled release capability.

Claims

1. A preparation method of a micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating is characterized by comprising the following steps:

1) dissolving one or more of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt and sodium salt in water to form electrolyte, immersing a titanium sample in the electrolyte by taking a titanium sample as an anode and a stainless steel tank as a cathode for micro-arc oxidation, and forming a micro-arc oxidation coating on the surface of the titanium; wherein, the micro-arc oxidation parameters are as follows: the micro-arc oxidation adopts pulse voltage, the positive voltage is 250-550V, the negative voltage is 0-100V, the micro-arc oxidation pulse frequency is 200-800 Hz, the duty ratio is 6-30%, and the micro-arc oxidation time is 5-15 min;

3) mixing a chitosan aqueous solution and a sodium alginate aqueous solution to obtain a mixed solution, adding a photoinitiator into the mixed solution, then dripping the mixed solution on a PDMS template provided with a plurality of holes, then placing a micro-arc titanium oxide sample on the template, irradiating by ultraviolet light, freezing and drying, and forming a chitosan/sodium alginate composite hydrogel coating on the micro-arc oxidation coating; wherein the mass ratio of the chitosan to the sodium alginate is 1: 10-10: 1; the irradiation time is 1-10 min. .

2. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 1), the titanium sample is TA2, TA3, TA4 industrial pure titanium or TC4 titanium alloy; the lithium salt is lithium phosphate, lithium silicate or lithium sulfate, the calcium salt is calcium phosphate, calcium dihydrogen phosphate, calcium silicate or calcium sulfate, the tin salt is stannic silicate, stannous sulfate or stannous pyrophosphate, the magnesium salt is magnesium silicate, magnesium sulfate or magnesium phosphate, the potassium salt is potassium silicate, potassium dihydrogen phosphate or potassium sulfate, and the sodium salt is disodium EDTA, sodium hydroxide, sodium sulfate, trisodium phosphate or sodium silicate.

3. The preparation method of the micro-arc oxidation titanium surface chitosan/sodium alginate composite hydrogel coating as claimed in claim 1, wherein in the step 1), the titanium sample is immersed in the electrolyte at 0-40 ℃ for micro-arc oxidation.

4. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 1), the concentration of lithium salt, calcium salt, tin salt, magnesium salt, potassium salt or sodium salt in the electrolyte is 5-30 g/L.

5. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 2), the curing temperature is 70-100 ℃.

6. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 3), the chitosan aqueous solution is prepared by the following steps: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10, and uniformly stirring to obtain a chitosan aqueous solution; the chitosan concentration in the chitosan aqueous solution is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of the amount of the chitosan substance.

7. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 3), the sodium alginate aqueous solution is prepared by the following steps: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10, and stirring to obtain sodium alginate aqueous solution; the concentration of sodium alginate in the sodium alginate aqueous solution is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of the alginic acid substance.

8. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 3), the addition amount of the photoinitiator is 0.05-0.2% of the volume of the mixed solution; the model of the photoinitiator is I2959; the ultraviolet light is realized by irradiating a 100W ultraviolet light lamp, and the ultraviolet intensity is 4800 mu W/cm²。

9. The method for preparing the micro-arc titanium oxide surface chitosan/sodium alginate composite hydrogel coating according to claim 1, wherein in the step 3), the diameter of the hole is 0.2-2mm, the depth of the hole is 0.2-2mm, and the shape of the hole is square, circular, triangular or star-shaped.