CN103933607B - The preparation method of the organic strontium coating of TC4 titanium alloy surface - Google Patents

Abstract

The invention discloses a method for preparing an organic strontium coating on the surface of a TC4 titanium alloy; a method for constructing a degradable organic strontium coating on the surface of a medical TC4 titanium alloy (Ti-6Al-4V) with the purpose of inducing bone quick fix. Based on the unique osteoinductivity of trace element strontium, strontium ions are loaded on the surface of titanium alloy through derivatives of carboxymethyl cellulose to prepare degradable organic strontium compounds. Through the degradation and release of strontium ions in the body, the purpose of growing new tissue on the surface of the implant and promoting rapid bone repair is achieved. The invention can solve the limitations of poor osteoinductivity of previous coatings, expensive growth factors, easy inactivation and short action time, and is beneficial to the development of cheap, efficient and stable osteoinductive materials.

Description

Preparation method of organic strontium coating on TC4 titanium alloy surface

technical field

The invention relates to a novel method for inducing rapid bone repair on the surface of a TC4 titanium alloy (Ti-6Al-4V) material modified with organic strontium, which is mainly used in the fields of biology, medicine, medical equipment and the like.

Background technique

Strontium (Strontium, Sr) is a trace element that is in the same group as calcium in the periodic table. In recent years, strontium has been found to have a unique uncoupling effect of enhancing osteogenic activity and inhibiting osteoclast resorption, which has great potential application value in orthopedics. Titanium alloy is widely used as the main material of orthopedic implants due to its excellent mechanical properties, strong corrosion resistance and good biocompatibility. However, titanium alloy is biologically inert, and its integration with the bone tissue at the implantation site is poor, and it is easy to separate from the surrounding host tissue and cause loosening. Research focus of medical titanium alloys. Existing inorganic coatings have limitations such as high brittleness, high residual stress, and poor osteoinductivity; organic polymers are the development trend of surface modification of titanium alloys, but they are not osteoinductive. In summary, the present invention proposes to synthesize organic strontium compounds to modify the surface of titanium alloys, and to promote the rapid repair of bone tissue at implant sites by controlling the degradation of materials and the release of strontium ions. This has a significant effect on improving the surgical effect of titanium alloy instruments, improving the quality of life of patients, and saving social medical resources.

Contents of the invention

The purpose of the present invention is to propose a key technology that can effectively improve the osteoinductivity of titanium alloy, promote the rapid integration of implant and bone, and can be used clinically.

By adjusting the molar ratio of reactants CMC-Na and DOPA·HCl to 1:1, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinyl Imine (NHS) activates the carboxymethyl group of CMC to prepare an organic compound (DOPA-CMC) with a strontium ion binding site. The organic strontium compound (DOPA-CMC-Sr) is obtained by chelating strontium ions through the carboxyl groups in the above organic matter.

DOPA-CMC-Sr preparation technology route

The preparation method of TC4 titanium alloy surface organic strontium coating of the present invention, the steps are as follows:

(1) Uniformly mix the aqueous solution of sodium carboxymethylcellulose and the trishydroxymethylaminomethane solution of dopamine hydrochloride in an equimolar amount under the action of a coupling agent;

(2) Add the aqueous solution of strontium chloride hexahydrate to the solution obtained in the above step (1), and mix evenly;

(3) Soak the titanium alloy sheet in the solution obtained in step (2), and react in the dark, overnight, take it out and dry it, and then obtain the organic strontium coating on the surface of the TC4 titanium alloy; as shown in Figure 1.

The TC4 titanium alloy sheet selected as the coating substrate can be pretreated first. After being polished and cleaned by water sandpaper, it is pretreated by nitric acid and sodium hydroxide successively, and dried for later use.

The molecular weight of the sodium carboxymethylcellulose is preferably 100kDa-250kDa. (kDa is the molecular mass unit of protein in biology).

The concentration range of said dopamine hydrochloride is preferably 1 mg/ml-5 mg/ml.

The coupling agent in the step (1) is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC)/N-hydroxysuccinimide (NHS).

The concentration of strontium ions in the mixed solution obtained in the step (2) is 5 mg/ml-15 mg/ml.

Through the above method, modifying the surface of titanium alloy with organic strontium compounds can promote the rapid repair of bone. The invention can solve the limitations of poor osteoinductivity, expensive growth factors, easy inactivation and short action time of previous coatings, and is beneficial to the development of cheap, efficient and stable osteoinductive materials.

Description of drawings

Figure 1 Flow chart of the construction process of organic strontium coating on the surface of TC4 titanium alloy substrate;

Figure 2 Infrared spectrum (FT-IR) of DOPA-CMC and DOPA-CMC-Sr;

Fig. 3a Scanning electron microscope (SEM) spectrum of TC4 titanium alloy after acid-base treatment;

Figure 3b X-ray energy spectrum analysis (EDS) diagram of TC4 titanium alloy after acid-base treatment;

Fig. 4a Scanning electron microscope (SEM) spectrum of organic strontium coating on TC4 titanium alloy;

Figure 4b X-ray energy spectrum analysis (EDS) diagram of organic strontium coating on TC4 titanium alloy;

Figure 5a X-ray photoelectron spectroscopy (XPS) diagram of TC4 titanium alloy after acid-base treatment;

Figure 5b X-ray photoelectron spectroscopy (XPS) diagram of strontium-free organic coating on TC4 titanium alloy;

Figure 5c X-ray photoelectron spectroscopy (XPS) diagram of organic strontium coating on TC4 titanium alloy;

Fig. 5d X-ray photoelectron spectroscopy (XPS) diagram of strontium element in organic strontium coating on TC4 titanium alloy.

Detailed ways

The technology of the present invention and concrete implementation row are specified below:

Example 1:

The method of preparing an organic strontium coating using TC4 titanium alloy as a substrate uses the chelating properties of strontium ions and carboxyl groups to prepare organic strontium compounds, and utilizes the characteristics of the ortho-diphenol functional group of dopamine to be closely combined with the substrate to immobilize the organic strontium compounds on Titanium finish.

The TC4 titanium alloy as the substrate is a TC4 titanium alloy sheet with a size of 10*10*2mm ³

The process parameters for preparing the organic strontium coating on the surface of TC4 titanium alloy are:

HNO ₃ concentration and corrosion time: 40%, 40min

NaOH concentration and holding time: 5mol/L, 5h

DOPA·HCl concentration: 1mg/ml

SrCl ₂ ·6H ₂ O concentration: 5mg/ml

The preparation method of above-mentioned coating and steps thereof are as follows:

(1) The sample is processed into 10×10×2mm ³ by wire cutting, polished with 600#, 800#, 2500# sandpaper respectively, ultrasonically cleaned with anhydrous ethanol, and dried.

(2) The surface of the above sample was pretreated with acid and alkali, corroded in 40% HNO ₃ solution for 40 minutes, and kept in 5mol/L NaOH solution at 90°C for 5 hours, cleaned with deionized water, and deionized water. Sonicate for 15 minutes and dry for later use.

(3) Prepare a 1% CMC aqueous solution, add an equimolar amount of EDC to the solution, stir for 15 minutes under a magnetic stirrer, then add an equimolar amount of NHS, and react for 40 minutes.

(4) Prepare a Tris solution of 1mg/ml DOPA·HCl, pH=8.5, so that it can be fully dissolved in a dark environment.

(5) Add the solution of step (4) into the solution of step (3), and stir for 1 hour under a magnetic stirrer until the solution becomes a homogeneous solution.

(6) Prepare the SrCl ₂ ·6H ₂ O solution, filter it into the solution obtained in step (5) with a 0.22um filter, and fully dissolve it so that the concentration of strontium ions in the mixed solution is 5 mg/ml.

(7) Soak the sample prepared in step (1) in the solution obtained in step (6) for 24 hours, and store in the dark. After the sample was taken out, the solution on the titanium sheet was dried, washed several times with deionized water, and dried in a drying oven at 56°C to obtain an organic strontium coating on the surface of the TC4 titanium alloy.

Example 2:

The method for preparing an organic strontium coating with TC4 titanium alloy as a substrate is characterized in that: the organic strontium compound is prepared by using the chelating characteristics of strontium ions and carboxyl groups, and the organic strontium compound is prepared by using the characteristics of the ortho-diphenol functional group of dopamine to be closely combined with the substrate. Compounds are immobilized on the surface of titanium alloy.

The TC4 titanium alloy as the substrate is a TC4 titanium alloy sheet with a size of 10*10*2mm ³

The process parameters for preparing the organic strontium coating on the surface of TC4 titanium alloy are:

HNO ₃ concentration and corrosion time: 50%, 1h

NaOH concentration and holding time: 5mol/L, 7h

DOPA·HCl concentration: 5mg/ml

SrCl ₂ 6H ₂ O concentration: 10mg/ml

The preparation method of the above-mentioned coating and the steps thereof are as follows:

(1) The sample is processed into 10×10×2mm ³ by wire cutting, polished with 600#, 800#, 2500# sandpaper respectively, ultrasonically cleaned with anhydrous ethanol, and dried.

(2) The surface of the above sample was pretreated with acid and alkali, corroded in 50% HNO ₃ solution for 1 hour, and then kept in 5mol/L NaOH solution for 7 hours at 90°C, cleaned with deionized water, and anhydrous ethanol Sonicate for 15 minutes and dry for later use. (3) Prepare a 1% CMC aqueous solution, add an equimolar amount of EDC to the solution, stir for 15 minutes under a magnetic stirrer, then add an equimolar amount of NHS, and react for 40 minutes.

(4) Prepare a Tris solution of 5mg/ml DOPA·HCl, pH=8.5, and make it fully dissolve in a dark environment.

(5) Add the solution of step (4) into the solution of step (3), and stir for 1 hour under a magnetic stirrer until the solution becomes a homogeneous solution.

(6) Prepare the SrCl ₂ ·6H ₂ O solution, filter it into the solution obtained in step (5) with a 0.22um filter, and fully dissolve it so that the concentration of strontium ions in the mixed solution is 10mg/ml.

(7) Soak the sample prepared in step (1) in the solution obtained in step (6) for 24 hours, and store in the dark. After the sample was taken out, the solution on the titanium sheet was dried, washed several times with deionized water, and dried in a drying oven at 56°C to obtain an organic strontium coating on the surface of the TC4 titanium alloy.

Example 3:

The method for preparing an organic strontium coating with TC4 titanium alloy as a substrate is characterized in that: the organic strontium compound is prepared by using the chelating characteristics of strontium ions and carboxyl groups, and the organic strontium compound is prepared by using the characteristics of the ortho-diphenol functional group of dopamine to be closely combined with the substrate. Compounds are immobilized on the surface of titanium alloy.

The TC4 titanium alloy as the substrate is a TC4 titanium alloy sheet with a size of 10*10*2mm ³

The process parameters for preparing the organic strontium coating on the surface of TC4 titanium alloy are:

HNO ₃ concentration and corrosion time: 60%, 2h

NaOH concentration and holding time: 5mol/L, 5h

DOPA·HCl concentration: 5mg/ml

SrCl ₂ 6H ₂ O concentration: 15mg/ml

The preparation method of the above-mentioned coating and the steps thereof are as follows:

(1) The sample is processed into 10×10×2mm ³ by wire cutting, polished with 600#, 800#, 2500# sandpaper respectively, ultrasonically cleaned with anhydrous ethanol, and dried.

(2) The surface of the above sample was pretreated with acid and alkali, corroded in 60% HNO ₃ solution for 2 hours, and kept in 5mol/L NaOH solution at 90°C for 5 hours, cleaned with deionized water, anhydrous ethanol Sonicate for 15 minutes and dry for later use.

(3) Prepare a 1% CMC aqueous solution, add an equimolar amount of EDC to the solution, stir for 15 minutes under a magnetic stirrer, then add an equimolar amount of NHS, and react for 40 minutes.

(4) Prepare a Tris solution of 5mg/ml DOPA·HCl to fully dissolve it in a dark environment.

(5) Add the solution of step (4) into the solution of step (3), and stir for 1 hour under a magnetic stirrer until the solution becomes a homogeneous solution.

(6) Prepare SrCl ₂ ·6H ₂ O solution, filter it into the solution obtained in step (5) with a 0.22um filter, and fully dissolve it so that the concentration of strontium ions in the mixed solution is 15mg/ml.

(7) Soak the sample prepared in step (1) in the solution obtained in step (6) for 24 hours, and store in the dark. After the sample was taken out, the solution on the titanium sheet was dried, washed several times with deionized water, and dried in a drying oven at 56°C to obtain an organic strontium coating on the surface of the TC4 titanium alloy.

The characterization methods and effects are as follows:

(1) Use the infrared spectrum (FT-IR) diagram to characterize the above organic matter, as shown in Figure 2. In the characteristic spectrum, the characteristic peaks of C=O (1700cm ^-1 ) and NH (1490cm ^-1 ) can be found correspondingly, which proves the formation of amide bonds in the polymer. In addition, it can also be found from the comparison of the results before and after the chelation of strontium that the change trend of the infrared spectrum is similar, which proves that the chelation of strontium does not change the main chain structure of the polymer. In order to prove that strontium ions are chelated into the polymer and to quantitatively analyze the chelated strontium, organic strontium compounds were subjected to ICP-MS test after microwave digestion. The test results show that the content of Sr element in the sample is: 70.099mg/g.

(2) In order to improve the bonding strength between the coating and the substrate, dopamine is used to combine with the titanium alloy substrate. The process flow for constructing the organic strontium coating on the surface of the TC4 titanium alloy substrate is shown in Figure 1. The DOPA-CMC prepared above is combined with the titanium alloy substrate by using the characteristics of the close combination of the ortho-diphenol functional group and the substrate, and finally through the combination with strontium ions Chelation forms an organic strontium coating on its surface. The surface morphology of the substrate before and after loading the organic strontium coating was observed with a scanning electron microscope (SEM), as shown in Figure 3a and Figure 4a. Figure 3a shows the surface morphology of the substrate before the organic strontium coating is loaded, and the surface of the substrate is porous. Figure 4a shows the surface morphology of the loaded organic strontium coating. Through the comparison of the two figures, it can be seen that there is a significant difference in the surface morphology of the titanium alloy before and after the loading of the coating. In the latter, it can be seen that there is a gel-like layer The substances are evenly loaded on the surface of the substrate. The composition and structure of the products formed on the surface of the titanium alloy substrate were characterized by X-ray energy spectroscopy and X-ray photoelectron spectroscopy, as shown in Figure 3b, Figure 4b and Figure 5. From the comparison of X-ray energy spectra in Figure 3b and Figure 4b, it can be found that compared with the substrate before loading the organic strontium coating (Figure 3b), the surface of the substrate after loading the organic strontium coating has a peak corresponding to Sr, and the Ti The peaks corresponding to the elements weakened, indicating that the organic strontium coating covered the substrate, as shown in Figure 4b. In addition, X-ray photoelectron spectroscopy (XPS) was used to characterize the composition of the substrate before and after the organic strontium coating was loaded. Compared with the XPS spectrum before loading the coating (Figure 5a), it can be found from Figure 5b/5c that After the coating is loaded, the peak corresponding to Ti on the surface of the titanium alloy gradually weakens or disappears. After the strontium element is chelated, the peak corresponding to Sr appears in Figure 5c, and it is in the 3d orbital at the binding energy of 133.919 (shown in Figure 5d) From the above results, it can be verified again that the organic strontium coating can be uniformly distributed on the surface of the titanium alloy substrate in the form of polymer.

(3) The in vitro degradation performance of the composite material was tested in simulated body fluid, and the release behavior of strontium ions was monitored by atomic absorption spectroscopy; through the above characterization, the relationship between the organic strontium structure and degradation characteristics was summarized, and the organic structure was further optimized.

Claims (3)

1. a preparation method of TC4 titanium alloy surface organic strontium coating, it is characterized in that the steps are as follows: (1) configure sodium carboxymethyl cellulose aqueous solution, add equimolar EDC to the solution, stir under a magnetic stirrer for 15 minutes, then add equimolar NHS, and react for 40 minutes; (2) Prepare a tris solution of dopamine hydrochloride of 1 mg/ml to 5 mg/ml, pH=8.5, so that it can be fully dissolved in a dark environment; (3) Add the solution of step (2) to the solution of step (1), so that the molar ratio of sodium carboxymethylcellulose to dopamine hydrochloride is 1:1, and stir under a magnetic stirrer until the solution is a homogeneous solution ; (4) Configure the SrCl ₂ ·6H ₂ O solution, filter it into the solution obtained in step (3) using a 0.22 μm filter, and fully dissolve it. The concentration of strontium ions in the mixed solution is 5 mg/ml-15 mg/ml; (5) Soak the TC4 titanium alloy sheet in the solution obtained in step (4) for 24 hours, and store it away from light; take the sample out and let the solution on the titanium sheet dry, wash it with deionized water several times, and put it in 56°C drying in a drying oven to obtain an organic strontium coating on the surface of the TC4 titanium alloy. 2. The method as claimed in claim 1, characterized in that: TC4 titanium alloy sheet is used as the coating substrate, pre-treated first, after being polished and cleaned by water sandpaper, pre-treated by nitric acid and sodium hydroxide successively, and dried . 3. The method according to claim 1, characterized in that: the molecular weight of the sodium carboxymethylcellulose is 100kDa～250kDa.