CN108939146A - A kind of antibacterial/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and preparation method thereof - Google Patents
A kind of antibacterial/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of antibacterials/anti-osteosarcoma/facilitate bone multifunctionality titanium-based implantation material preparation method；The present invention passes through micro-arc oxidation treatment in the hydroxyapatite porous coating of titanium surface building strontium ion doping first；Then sample is placed in the autoclave containing 2,5-Dihydroxyterephthalic acid and magnesium nitrate, is reacted under the conditions of 125 DEG C for 24 hours, obtain metal organic framework coating on surface；Obtained Mg-MOF74/Sr-HA composite coating modification sample shows superior antibacterial, anti-osteosarcoma and promotees osteogenic characteristics, has good potential applicability in clinical practice.
Description
Technical field
The present invention relates to biomedical materials field, specifically a kind of antibacterial/anti-osteosarcoma/facilitates bone multifunctionality titanium-based
It is implanted into the preparation method of material.
Background technique
In recent years, bacterium infection has proved to be the second largest factor for causing orthopaedics implant surgery failure.Studies have shown that sense
4-6 hour after dye is the critical period of bacterium treatment.In the stage, intrusion bacterium will be attached to implant surfaces and largely expand
Increase, and then protect internal bacterium to encroach on from antibacterial material after forming fine and close mycoderm layer, such mycoderm also will largely hinder
The early stage between implant and surrounding bone is hindered to be integrated.
In addition, there is free osteosarcoma cell residual after bone and flesh resection of the tumor, such cell may also will lead to swollen more
Tumor recurrence, damage Integrated implant process.
Therefore, it is directed to the patient of osteosarcoma excision or bacillary secondary revision procedure, research and development have early stage antibacterial, anti-bone
Sarcoma and facilitate the more performances of bone orthopedic implanting material have biggish application prospect.
Summary of the invention
Present invention aim to address problems of the prior art, provide a kind of antibacterial/anti-osteosarcoma/and facilitate bone more
The preparation method of functional titanium-based implantation material.
To realize the present invention purpose and the technical solution adopted is that such, a kind of antibacterial/anti-osteosarcoma/facilitates the more function of bone
The preparation method of energy property titanium-based implantation material, which comprises the following steps:
1) by micro-arc oxidation treatment, in hydroxyapatite (Sr-HA) porous painting of titanium surface building strontium ion doping
Layer；
2) hydro-thermal reaction approach is utilized, constructs metal organic framework Mg- in the hydroxyapatite surface of strontium ion doping
MOF74 coating.
Further, the process of Sr-HA porous coating is constructed on titanium surface by micro-arc oxidation treatment in the step 1)
Are as follows:
1.1) titanium foil after will be pretreated immerses in electrolyte, is reacted under voltage, sample is obtained after 5~30min
This；
It include strontium acetate, calcium acetate, β sodium glycero-phosphate and water in the electrolyte；
The concentration of the strontium acetate is less than 0.3M；
The concentration of the calcium acetate is 0.1~0.3M；
The concentration of the β sodium glycero-phosphate is 0.1~0.3M；
The voltage range is 300~600V；
1.2) sample obtained in step 1.1) is placed in deionized water after being cleaned by ultrasonic, is dried for standby.
Further, the preprocessing process in the step 1.1) are as follows: after being cut titanium foil, successively use ethyl alcohol, third
Ketone and deionized water respectively wash 5~20min；It is spare after drying process.
Further, in the ultrasonic cleaning process in the step 1.2): supersonic frequency be 30~50KHz, the time be 0.5~
2min。
Further, hydro-thermal reaction approach is utilized in the step 2), constructs metal organic framework Mg- on the surface Sr-HA
The process of MOF74 coating are as follows:
2.1) electrolyte containing magnesium nitrate and 2,5- dihydric para-phthalic acid is configured；
The solvent of the electrolyte includes dimethylformamide, ethyl alcohol and deionized water；
The volume (mL) of the dimethylformamide, ethyl alcohol and deionized water than for (54~74) ︰ (0~10) ︰ (0~
10)；
The w/v (g ︰ mL) of the magnesium nitrate and dimethylformamide is (0.5~1.0) ︰ (54~74)；
The w/v (g ︰ mL) of the 2,5- dihydric para-phthalic acid and dimethylformamide is (0.2~0.5) ︰
(54~74)；
2.2) the Sr-HA sample after micro-arc oxidation treatment obtained in step 1) is immersed into configured electricity in step 2.1)
It solves in liquid, 12~48h is reacted under the conditions of being placed in 80~150 DEG C.
One kind facilitating bone by the described in any item preparation methods of Claims 1 to 5 antibacterial obtained/anti-osteosarcoma/
Multi-functional titanium-based is implanted into material.
It is worth noting that: titanium and its alloy are as a kind of common dentistry and bone material, owned good life
Object compatibility and mechanical property etc..But studies have shown that titanium base material shows strong biologically inert, significantly limit implant
The early stage Integrated implant of surrounding.In order to improve their biocompatibility and osteogenic ability, researchers usually using it is normal or from
The hydroxyapatite coating layer of son doping is surface modified material.
Further analysis shows, the metallic element for hydroxyapatite coating layer doping is mostly magnesium, copper, zinc, strontium etc..Its
In, strontium ion is indispensable element in bone tissue forming process, and 20% strontium ion doping increases hydroxyl with can dramatically
The early stage bon e formation and Integrated implant inducibility of phosphorus ash stone implant.So the present invention has selected Sr-HA coating to improve
The rush bone formation performance of titanium.
In recent years, metal-organic framework materials (MOFs) are since its regularity, porosity and catalysis characteristics etc. are by more next
More concerns, and people develop the functionalization anti-biotic material of a series of novel using it.In general, in aqueous solution, MOFs
Material can due to hydrone interference and gradually degrade, and the degradation rate of material can be accelerated significantly under acidic environment.Cause
This, for the present invention in the composite coating of titanium surface building Sr-HA and Mg-MOF74, it is superior anti-that which will assign titanium implants
Bacterium, anti-osteosarcoma and rush bone formation performance.
The solution have the advantages that unquestionable, the invention has the following advantages that
1) present invention in preparation method it is easy to operate, reproducible, controllability is strong；
2) have superior early stage antibacterial, anti-osteoma and rush using the Multifunctional titanium implant of the method preparation in the present invention
Osteogenic characteristics, possess good potential applicability in clinical practice, there is important researching value and clinical meaning in bone graft technique.
Detailed description of the invention
Fig. 1 is surface scan Electronic Speculum (SEM) figure of different samples；
Fig. 2 is X-ray diffraction (XRD) map of different samples；
Fig. 3 is the SEM figure of different materials surface staphylococcus aureus and Escherichia coli；
After Fig. 4 is for culture 6 and for 24 hours, the bacteriostasis rate statistical chart of different materials surface staphylococcus aureus；Confidence interval is
99.9% (p < 0.01 * *)；
After Fig. 5 is for culture 6 and for 24 hours, the bacteriostasis rate statistical chart of different materials surface Escherichia coli；Confidence interval is 99.9%
(**p<0.01)；
Fig. 6 is osteosarcoma cell (Saos-2cells) and osteoblast (osteoblasts) at normal or pre-soaking 1d
FDA fluorogram after reason, after each sample surface culture 3 days；
Fig. 7 is the alkalinity of osteoblast (osteoblasts) after pre-soaking 1d processing, after each sample surface culture 7 days
The quantitative data statistical chart of phosphatase (ALP) activity, collagen expression and mineralising dyeing；Confidence interval be 99.9% (* * p <
0.01)；
As shown in figure 8, under the conditions of as pH 7.4 or 6.5, after Sr-HA-MOF74 sample impregnates different time sections, 2,5-
The release statistical chart of dihydric para-phthalic acid (DHTA)；
As shown in figure 9, under the conditions of as pH 7.4 or 6.5, after Sr-HA-MOF74 sample impregnates different time sections, magnesium from
Son (Mg2+) release statistical chart；
As shown in Figure 10, as under the conditions of various concentration DHTA, staphylococcus aureus, Escherichia coli, osteosarcoma cell
And the cell activity statistical chart of osteoblast；
As shown in figure 11, as various concentration Mg2+Under the conditions of, staphylococcus aureus, Escherichia coli, osteosarcoma cell and
The cell activity statistical chart of osteoblast；
As shown in figure 12, after as different materials are soaked in the broth bouillon of culture staphylococcus aureus, when different
Between put when sample surface local ph variation diagram；
As shown in figure 13, after as different materials are soaked in the broth bouillon of culture Escherichia coli, when different time points
The local ph variation diagram of sample surface；
As shown in figure 14, after as different materials are soaked in the cell DMEM culture medium of culture osteosarcoma cell, when different
Between put when sample surface local ph variation diagram；
As shown in figure 15, as Sr-HA-MOF74 sample antibacterial, anti-osteosarcoma and the potential mechanism schematic diagram for facilitating bone.
Specific embodiment
Below with reference to embodiment, the invention will be further described, but should not be construed the above-mentioned subject area of the present invention only
It is limited to following embodiments.Without departing from the idea case in the present invention described above, according to ordinary skill knowledge and used
With means, various replacements and change are made, should all include within the scope of the present invention.
Embodiment 1:
A kind of antibacterial/anti-osteosarcoma/facilitates the preparation method of bone multifunctionality titanium-based implantation material, which is characterized in that packet
Include following steps:
1) by micro-arc oxidation treatment, in hydroxyapatite (Sr-HA) porous painting of titanium surface building strontium ion doping
Layer；
1.1) titanium foil after will be pretreated immerses in electrolyte, is reacted under voltage, sample is obtained after 10min；
It include strontium acetate, calcium acetate, β sodium glycero-phosphate and water in the electrolyte；
The concentration of the strontium acetate is 0.05M；The concentration of the calcium acetate is 0.15M；The concentration of the β sodium glycero-phosphate
For 0.2M；
The voltage is 550V；
The preprocessing process are as follows: after 20 titanium foils (1 × 1 centimetre) of pre-cut are cut, successively using ethyl alcohol,
Acetone and deionized water respectively wash 10min；It is spare after drying process.
1.2) sample obtained in step 1.1) is placed in deionized water after being cleaned by ultrasonic, is dried for standby.
In the ultrasonic cleaning process: supersonic frequency 40KHz, time 1min.
2) hydro-thermal reaction approach is utilized, constructs metal organic framework Mg- in the hydroxyapatite surface of strontium ion doping
MOF74 coating.
2.1) electrolyte of the magnesium nitrate containing 356mg and the 2,5- dihydric para-phthalic acid of 167mg is configured；
The solvent of the electrolyte includes dimethylformamide, ethyl alcohol and deionized water；
The volume of the dimethylformamide, ethyl alcohol and deionized water is respectively 65,4.5 and 4.5mL；
2.2) then 37mL electrolyte is poured into the autoclave polytetrafluoroethylliner liner that capacity is 100mL, will be walked
It is rapid 1) obtained in Sr-HA sample after micro-arc oxidation treatment immerse in electrolyte, reacted for 24 hours under the conditions of being placed in 125 DEG C.
Scanning electron microscope (SEM) picture of step 1) and step 2) preparation gained sample is as shown in Figure 1；
As can be seen from Figure 1: pure titanium surface is with the presence of more scratch structure；After micro-arc oxidation treatment, the surface Sr-HA table
It is now in uniform porous structure；And further after hydro-thermal reaction processing, Sr-HA-MOF74 sample surface has nutty structure shape
At.
Show that purpose functional coating is successfully prepared on titanium surface from the pattern variation in Fig. 1, and the conclusion obtains
The further verifying of X-ray diffraction as shown in Figure 2 (XRD) result.
From the XRD in Fig. 2 statistics indicate that: compared with pure titanium group, anatase/rutile type TiO2And Sr-HA new peak is in Sr-
Occur in HA and Sr-HA-MOF74 sample, and Mg-MOF74 correlation spectral peak is only characterized in the latter.
In conjunction with the above results it is found that purpose material is successfully prepared.
Experimental example 1:
Sample surface ne ar and antimicrobial efficiency detection
It the use of initial concentration is 2 × 106The staphylococcus aureus (S.aureus, ATCC29213) of a/mL and large intestine bar
Bacterium (E.coli, ATCC2592) bacterium solution carries out germ experiment；Specifically includes the following steps:
It 1) is 4% using concentration after two kinds of bacteriums (1mL) being inoculated in different materials surface 6 hours respectively (37 DEG C)
Paraformaldehyde solution is pre-fixed (40min) to surface adhesion bacterium；
2) then bacterium is carried out dehydrating using graded ethanol solutions, SEM observation finally is carried out to bacteria sample；
In addition, microbionation 6 and for 24 hours after, the Adherent bacteria on different materials surface is separated and collected by ultrasonic approach,
Then it is characterized using antimicrobial efficiency of the bacterium spread plate method to different samples.
Experimental result is as seen in figures 3-5；It is specific:
As shown in figure 3, the as SEM of different materials surface staphylococcus aureus and Escherichia coli schemes；
As shown in figure 4, be culture 6 and for 24 hours after, the bacteriostasis rate statistical chart of different materials surface staphylococcus aureus；
Confidence interval is 99.9% (p < 0.01 * *)；
As shown in figure 5, be culture 6 and for 24 hours after, the bacteriostasis rate statistical chart of different materials surface Escherichia coli；Confidence area
Between be 99.9% (p < 0.01 * *)；
As can be seen from Figure 3: after culture 6 hours, the surface Sr-HA-MOF74 is with the presence of least bacterium, and Sr-HA sample
This also shows certain anti-microbial property, this may be closely related with the porous structure of material surface.
From equally can be seen that in the bacteriostasis rate result in Fig. 4 and Fig. 5 culture 6 and for 24 hours after, the antibacterial ability of three kinds of materials
Trend is Sr-HA-MOF74 > Sr-HA > Ti；When two time points, the antibacterial efficiency of Sr-HA-MOF74 sample is all larger than 80%.
Therefore it can be concluded that compared to other two groups of materials, Sr-HA-MOF74 has superior anti-microbial property.
Experimental example 2:
The detection of material surface human osteosarcoma cell proliferation
It the use of initial concentration is 2 × 104The Saos-2 cell in a/hole is inoculated in material surface, utilizes work after culture 3 days
Property fluorescein diacetate (FDA) Coloration experiment probes into the proliferation of each group osteosarcoma cell (Saos-2cells)；
In the detection, in order to prepare FDA color card, the FDA dye liquor (10 μ g/mL) of 2 μ L is added to cell culture medium,
After cell incubation 10min, remaining dye liquor is removed using PBS buffer solution；After finally using fluorescence microscope (FM) to dyeing
Saos-2 living cells carries out observation analysis；
Experimental result is as shown in fig. 6, specific:
As shown in fig. 6, as osteosarcoma cell (Saos-2cells) and osteoblast (osteoblasts) in normal or
After pre-soaking 1d processing, the FDA fluorogram after each sample surface culture 3 days；
As can be known from Fig. 6: after culture 3d, for Sr-HA-MOF74 sample surface with the presence of least Saos-2 living cells, this is existing
As may be related with the MOF74 coating degradation of material surface；
In addition, due to release property Ca2+And Sr2+Deng presence, Sr-HA sample group osteosarcoma cell shows stronger proliferation
Trend.
The above results show that purpose Sr-HA-MOF74 sample possesses the anti-osteosarcoma potential in strong part.
Experimental example 3:
Material surface osteoblastic proliferation and Osteoblast Differentiation performance detection
Each sample is divided into Presoak (0d) and Presoak (1d) two groups: Presoak (0d) group in osteoblast experiment
Middle material is used directly inoculating cell；And it need to be in PBS solution in advance before material inoculation osteoblast in Presoak (1d) group
Impregnate 1d.
Initial concentration is 2 × 104The Primary osteoblast cells in a/hole are inoculated in material surface and utilize FDA after culture 3 days
Coloration experiment probes into the proliferation of each group osteoblast；
The skeletonization of alkaline phosphatase (ALP) expression, collagen secretion and mineralization experiments detection group of cells is utilized after culture 7 days
Level of differentiation；In the detection, FDA experiment flow is identical as experimental example 2；
In order to carry out ALP activity, collagen expression and mineralising level characterization, osteoblast are cultivated 7 days in different materials surface
Afterwards, commercialized ALP staining kit, ALP activity detection kit, collagen staining kit and alizarin red dye liquor are used respectively
It carries out dyeing and quantitative analysis, detailed process can refer to detailed kit specification；
Experimental result is as shown in fig. 7, specific:
As shown in fig. 7, as osteoblast (osteoblasts) is after pre-soaking 1d processing, each sample surface culture 7 days
Alkaline phosphatase (ALP) activity, collagen expression and the quantitative data statistical chart of mineralising dyeing afterwards；Confidence interval is 99.9%
(**p<0.01)；
It can be seen that from the FDA result in Fig. 6, the osteoblast for not impregnating Sr-HA-MOF74 sample surface only shows
Lower cell Proliferation, but after pre-soaking processing, this group of cells show goes out superior related biological performance, this illustrates surface layer
After Mg-MOF74 coating degradation, exposed Sr-HA coating can substantially improve the cell compatibility of titanium-based material.
In addition, collagen and mineralising dyeing and quantitative analysis results also indicate that, Sr-HA and pre-soaking Sr- from the ALP in Fig. 7
HA-MOF74 group osteoblast possesses strong ALP activity, and collagen secretion and mineralising are horizontal, this shows that two groups of materials can be effectively
Promote cell Osteoblast Differentiation.
The above results show that surface layer MOF74 shows certain cell toxicant to osteoblast in Sr-HA-MOF74 sample
Property, but the Sr-HA coating exposed after its fast degradation promotes osteoblastic proliferation and Osteoblast Differentiation performance in which can dramatically.
Experimental example 4:
Sr-HA-MOF74 sample antibacterial, anti-osteoma and rush Osteogenic Mechanism are probed into
Sr-HA-MOF74 sample is soaked in the PBS solution (5mL) of pH7.4 or 6.5, in different time points (0,6,
12,24,48 and 72h) when collect release liquid, it is right respectively using ultraviolet specrophotometer (352nm) and Atomic Absorption Spectrometer
DTHA and Mg2+Burst size characterized；
With reference to the DTHA and Mg of Sr-HA-MOF742+Burst size screens DTHA (0,0.5,1,2,3 and of serial various concentration
4 μM) and Mg2+(0,1,2,4 and 8 μM), and them are probed into staphylococcus aureus, Escherichia coli, Saos-2 using MTT experiment
The potential cytotoxicity of cell and osteoblast；
It is carried out finally, the local ph of material surface and interface changes using miniature pH meter, when to bacterium and osteoma cell culture
Measurement；
Experimental result is as shown in Fig. 8~11 and Figure 12~15；
As shown in figure 8, under the conditions of as pH 7.4 or 6.5, after Sr-HA-MOF74 sample impregnates different time sections, 2,5-
The release statistical chart of dihydric para-phthalic acid (DHTA)；
As shown in figure 9, under the conditions of as pH 7.4 or 6.5, after Sr-HA-MOF74 sample impregnates different time sections, magnesium from
Son (Mg2+) release statistical chart；
As shown in Figure 10, as under the conditions of various concentration DHTA, staphylococcus aureus, Escherichia coli, osteosarcoma cell
And the cell activity statistical chart of osteoblast；
As shown in figure 11, as various concentration Mg2+Under the conditions of, staphylococcus aureus, Escherichia coli, osteosarcoma cell and
The cell activity statistical chart of osteoblast；
It is can be found that from the releasing result in Fig. 8 and 9: when normal pH 7.4, DTHA and Mg2+The time all discharged is about
For 48h, and 12 hours are only needed to be released completely under acid condition (pH 6.5).
As a result it can also be seen that DTHA and Mg in2+Total volume respectively may be about 3.6 and 7.4 μM, and two under acid condition
Person is more than 90% in the release efficiency of 6h.
It is can be found that in conjunction with the result in Figure 10 and 11: 7.4 μM of Mg2+It is non-toxic to bacterium and cell to generate, and
DTHA (3.6 μM) are more toxic, this illustrates that high concentration DTHA may be Sr-HA-MOF74 material early stage antibacterial, anti-osteosarcoma
Inducement.
As shown in figure 12, after as different materials are soaked in the broth bouillon of culture staphylococcus aureus, when different
Between put when sample surface local ph variation diagram；
As shown in figure 13, after as different materials are soaked in the broth bouillon of culture Escherichia coli, when different time points
The local ph variation diagram of sample surface；
As shown in figure 14, after as different materials are soaked in the cell DMEM culture medium of culture osteosarcoma cell, when different
Between put when sample surface local ph variation diagram；
As shown in figure 15, as Sr-HA-MOF74 sample antibacterial, anti-osteosarcoma and the potential mechanism schematic diagram for facilitating bone；
From pH result of variations shown in Figure 12~14 it can be seen that when MOF coating degradation, the Mg of release property2+Can be
Sr-HA-MOF74 constructs local culture medium alkalinity microenvironment (pH is about 8), which can also inhibit bacterium to a certain extent
And the growth of osteosarcoma cell.
Therefore, the antibacterial of Sr-HA-MOF74 sample, anti-osteosarcoma and rush Osteogenic Mechanism may be summarized as follows: as shown in figure 15,
The acidic micro-environment of bacterium or osteosarcoma cell can lead to Mg-MOF74 fast degradation, the alkaline microenvironment and high concentration of generation
DHTA can induce local bacterial and osteosarcoma cell is dead；After the completion of MOF coating degradation, exposed Sr-HA coating can be efficiently
Induced osteogenesis cell Proliferation and Osteoblast Differentiation, and then promote new bone formation.
Therefore, one aspect of the present invention, by surface layer Mg-MOF74 assign the superior local antibacterial of Sr-HA-MOF74 sample and
Anti- osteosarcoma performance, on the other hand, the Sr-HA coating exposed after Mg-MOF74 degradation can be effectively facilitated osteoblast increasing
It grows, active and Osteoblast Differentiation, it is final to realize local bone injury in treating.
Claims (6)
1. a kind of antibacterial ,/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and preparation method thereof, which is characterized in that packet
Include following steps:
1) by micro-arc oxidation treatment, Sr-HA porous coating is constructed on titanium surface；
2) hydro-thermal reaction approach is utilized, is applied in the hydroxyapatite surface building metal organic framework Mg-MOF74 of strontium ion doping
Layer.
2. a kind of antibacterial according to claim 1 ,/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and its preparation
Method, it is characterised in that:
The process of Sr-HA porous coating is constructed on titanium surface by micro-arc oxidation treatment in the step 1) are as follows:
1.1) titanium foil after will be pretreated immerses in electrolyte, is reacted under certain voltage, sample is obtained after 5~30min
This；
It include strontium acetate, calcium acetate, β sodium glycero-phosphate and water in the electrolyte；
The concentration of the strontium acetate is less than 0.3M；
The concentration of the calcium acetate is 0.1~0.3M；
The concentration of the β sodium glycero-phosphate is 0.1~0.3M；
The voltage range is 300~600V；
1.2) sample obtained in step 1.1) is placed in deionized water after being cleaned by ultrasonic, is dried for standby.
3. a kind of antibacterial according to claim 2 ,/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and its preparation
Method, it is characterised in that: the preprocessing process in the step 1.1) are as follows: after being cut titanium foil, successively use ethyl alcohol, third
Ketone and deionized water respectively wash 5~20min；It is spare after drying process.
4. a kind of antibacterial according to claim 2 ,/anti-osteosarcoma/facilitates bone multifunctionality titanium-based implantation material and its preparation
Method, it is characterised in that: in the ultrasonic cleaning process in the step 1.2): supersonic frequency is 30~50KHz, time 0.5
~2min.
5. a kind of antibacterial according to claim 1 or 2/anti-osteosarcoma/facilitate bone multifunctionality titanium-based implantation material and its
Preparation method, it is characterised in that:
Hydro-thermal reaction approach is utilized in the step 2), in the mistake of the surface Sr-HA building metal organic framework Mg-MOF74 coating
Journey are as follows:
2.1) electrolyte containing magnesium nitrate and 2,5- dihydric para-phthalic acid is configured；
The solvent of the electrolyte includes dimethylformamide, ethyl alcohol and deionized water；
The volume (mL) of the dimethylformamide, ethyl alcohol and deionized water is than being (54~74) ︰ (0~10) ︰ (0~10)；
The w/v (g ︰ mL) of the magnesium nitrate and dimethylformamide is (0.5~1.0) ︰ (54~74)；
The w/v (g ︰ mL) of the 2,5- dihydric para-phthalic acid and dimethylformamide is (0.2~0.5) ︰ (54
~74)；
2.2) the Sr-HA sample after micro-arc oxidation treatment obtained in step 1) is immersed into configured electrolyte in step 2.1)
In, 12~48h is reacted under the conditions of being placed in 80~150 DEG C.
6. one kind facilitates bone more by the described in any item preparation methods of Claims 1 to 5 antibacterial obtained/anti-osteosarcoma/
Functional titanium-based is implanted into material.
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