阅读说明：本技术 光活化的植入体表面去污溶胶，其制法及应用 (Photoactivated implant surface decontamination sol, preparation method and application thereof ) 是由 田卫东 谢利 胡兴宇 于 2020-12-22 设计创作，主要内容包括：本发明公开了光活化的植入体表面去污溶胶,其制法及应用,解决现有技术中不能在不破坏植入体表面的前提下,杀灭残留细菌及清除残余细菌胞外多聚物的问题,属于植入体感染治疗技术领域。本发明的光活化的植入体表面去污溶胶由包括过氧化物、氧缺陷型二氧化钛、赋型剂、水为原料的组分制成,表面去污溶胶中包括1-300mg/mL氧缺陷型二氧化钛；表面去污溶胶中过氧化物质量浓度大于0.1小于等于40％。本发明应用了缺陷二氧化钛的光热,光催化和芬顿效应的协同效应,具有显著增强的杀菌去污效力。该去污溶胶具有温和广谱、不损伤正常组织和植入体表面原有结构或涂层、能彻底清洁植入体等优点,为感染植入体的去污清洁提供了一种有力的手段。(The invention discloses a photoactivated implant surface decontamination sol, a preparation method and application thereof, which solve the problems that the prior art can not kill residual bacteria and remove residual bacteria extracellular polymeric substances on the premise of not damaging the implant surface, and belong to the technical field of implant infection treatment. The photoactivated implant surface decontamination sol is prepared from components which take peroxide, oxygen-deficient titanium dioxide, an excipient and water as raw materials, wherein the surface decontamination sol comprises 1-300mg/mL of oxygen-deficient titanium dioxide; the mass concentration of the peroxide in the surface decontamination sol is more than 0.1 and less than or equal to 40 percent. The invention applies the synergistic effect of photo-thermal, photo-catalytic and Fenton effects of defective titanium dioxide, and has obviously enhanced sterilization and decontamination effects. The decontamination sol has the advantages of mild broad spectrum, no damage to normal tissues and the original structure or coating on the surface of the implant, thorough cleaning of the implant and the like, and provides a powerful means for decontamination and cleaning of infected implants.)

1. The photoactivated implant surface decontamination sol is characterized by being prepared from components which take peroxide, oxygen-deficient titanium dioxide, an excipient and water as raw materials, wherein the surface decontamination sol comprises 1-300mg/mL of oxygen-deficient titanium dioxide; the mass concentration of the peroxide in the surface decontamination sol is more than 0.1 and less than or equal to 40 percent.

2. The surface decontamination sol of claim 1, wherein said surface decontamination sol comprises 40-80mg/mL oxygen deficient titanium dioxide, and wherein the mass concentration of peroxide in the surface decontamination sol is 2-10%.

3. Sol according to claim 1 or 2, characterized in that the peroxide comprises an inorganic peroxide or/and an organic peroxide; the inorganic peroxide is preferably hydrogen peroxide, and the organic peroxide is preferably carbamide peroxide, peracetic acid, benzoyl peroxide or di-tert-butyl peroxide.

4. The sol according to claim 1 or 2, characterized in that said oxygen deficient titanium dioxide has oxygen vacancies and trivalent titanium ions.

5. Sol according to claim 1 or 2, characterized in that the excipients comprise sodium alginate, carbomer.

6. The sol of claim 1 or 2, wherein the light comprises visible light or/and near infrared light, wherein the visible light band is 400-780nm, and the near infrared band is 780-2500 nm; the visible light is preferably a white light or monochromatic light source, and the near infrared light source may preferably be a laser light source with a wavelength of 808 nm.

7. The method for preparing a sol according to any one of claims 1 to 6, characterized by comprising the steps of:

step 1, preparing excipient sol: adding water into an excipient, and mixing to prepare excipient sol;

step 2, dispersing the oxygen-deficient titanium dioxide in water to prepare a suspension, adding the excipient sol prepared in the step 1, and uniformly mixing to obtain a working sol precursor;

and 3, uniformly mixing the peroxide solution and the working sol precursor to obtain the implant surface decontamination sol.

8. The production method according to claim 7,

in the suspension prepared in the step 2, the mass volume concentration of the oxygen-deficient titanium dioxide is as follows: 0.2-60 w/v%, wherein when the mass unit is g, the volume unit is mL;

in the step 3, the mass volume concentration of the peroxide solution is 0.2-40 w/v%, wherein when the mass unit is g, the volume unit is mL.

9. Use of a sol according to any one of claims 1 to 6 for the decontamination of the surface of an implant; preferably, the decontamination comprises sterilization or/and degradation of the biofilm; preferably the biofilm comprises extracellular matrix components secreted by bacteria, more preferably proteins, nucleic acids, polysaccharides, lipid macromolecules.

10. Use according to claim 9, wherein the implant comprises a dental implant, a bone plate, a bone screw, an artificial joint; preferably, the implant is made of titanium, titanium alloy, zirconium alloy, polyether ether ketone.

Technical Field

The invention belongs to the technical field of implant infection treatment, and particularly relates to photoactivated implant surface decontamination sol, and a preparation method and application thereof.

Background

The emergence of implants has greatly promoted the development of medicine. The artificial bone joint and the titanium plate titanium nail in the orthopaedics department play an important role in treating bone related diseases and dental implants in the aspect of treating tooth loss. However, infection is often accompanied around the implant, and is often caused by bacterial colonization. Bacteria can be killed by antibiotics in the early stage of infection, but often because the treatment is not timely and bacteria multiply in a large quantity, a bacterial biofilm is rapidly formed on the surface of an implant, and the treatment becomes very troublesome. The bacterial biofilm is not simply accumulated by bacteria, but is a three-dimensional network structure formed by bacteria and extracellular matrix (EPS) secreted by the bacteria, so that the bacterial biofilm has a strong buffering effect on external stimulation. The EPS mainly comprises polysaccharide and protein, and then biomacromolecules such as nucleic acid, lipid and the like, which are stacked together to protect the bacteria embedded therein like a fort, so that the effect of the antibiotic on the bacteria is weakened or even lost. Therefore, once a biological membrane is formed, antibiotic treatment is pale and weak, and if the treatment is not carried out in time, the conditions of implant loosening and falling off can occur along with the progress of periphytosis, and even more, bacteremia is caused to endanger life, so that the medical field of periphytosis treatment is a problem to be solved urgently. In order to effectively remove the biological membrane on the surface of the implant, the surgical debridement is matched with chemical medicines which are the most common means at present. The infected implant surface is exposed through an operation incision, and the biomembrane on the surface is mechanically removed, for example, the implant is usually treated by pulse flushing in orthopedics department, and the implant is subjected to surface treatment in the modes of scraping, sand blasting and the like in the dental implant. Although mechanical decontamination can remove most of the biofilm, the biofilm remains are inevitable, mainly due to the following reasons: 1) the special structure of the surface of the implant, such as the sand blasting and acid etching rough surface of the dental implant, makes the conventional decontamination apparatus difficult to reach the inside of the micron-sized pit. 2) The currently existing mechanical decontamination means in clinic have The problem of limited decontamination capability, such as pulse washing, and research by Charles M.Davis III et al (P μ Lse Lavage is Adadequate at Removal of Biofilm from The Surface of Total Knee Arthroplasty Materials, The Journal of Arthroplasty 29(2014) 1128-. 3) The uncontrollable operation of the operator and the operation of different doctors are different, and the debridement effect is good or bad. The residual biological membrane comprises residual bacteria and residual EPS, wherein the residual bacteria can be further killed by chemical drugs, such as 3% hydrogen peroxide, chlorhexidine and the like, but the drugs are mostly sterilized by local washing, and the use mode has the problems of short action time and limited capability of killing bacteria, so that viable bacteria can still remain on the surface of the implant after the chemical drug treatment, and secondly, the degradation effect of the chemical drugs on the biological membrane is limited, and the bacteria can be wrapped by the EPS and attached to the surface of the implant even if the bacteria are killed. The presence of inflammatory molecules such as G-bacterial cell wall component Lipopolysaccharide (LPS), G + bacterial cell wall component lipoteichoic acid (LTA) and the like in the biofilm component remaining on the surface of the implant can cause inflammation around the implant, and studies of Edward M.Greenfield (additive lipid polysaccharides inhibition of osseointegration of oral implants by lipid interference in Bone differentiation, Bone 52(2013) 93-101) show that LPS can inhibit dental implant osseointegration; the Donald Y.M. Leung (Staphylococcus aureus Lipoteicotic Acid Damages the Skin Barrier through an IL-1EMediated Pathway, Journal of Investigative Dermatology (2019)139) study showed that LTA can cause inflammation of soft tissues such as Skin. So at present, decontamination of infected implant surfaces is not an exhaustive scientific problem to be solved.

The clinical method for deeply decontaminating the surface of the infected implant mainly comprises a laser pulse method, an ultrasonic method, photodynamic therapy and the like. The laser has higher energy, so the coating on the surface of the implant can be damaged while the biomembrane is effectively removed by the laser, the biomembrane can be effectively removed by the ultrasonic wave, but the problem of residue also exists, and the photodynamic therapy has better killing effect on bacteria by singlet oxygen, but has limited degradation effect on the biomembrane similar to chemical drugs. Therefore, it is an urgent need to solve the problem of the art to provide an efficient and mild strategy for deeply decontaminating the surface of the infected implant to achieve the killing of residual bacteria and the complete removal of residual EPS without destroying the surface of the implant.

Disclosure of Invention

One of the objectives of the present invention is to provide a photoactivated implant surface decontamination sol, which solves the problems in the prior art that residual bacteria cannot be killed and residual EPS cannot be completely removed without damaging the implant surface.

The second purpose of the invention is to provide a preparation method of the implant surface decontamination sol.

The invention also aims to provide application of the decontamination sol on the surface of the implant.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

the photoactivated implant surface decontamination sol is prepared from components which take peroxide, oxygen-deficient titanium dioxide, an excipient and water as raw materials, wherein each mL of the surface decontamination sol comprises 1-300mg of the oxygen-deficient titanium dioxide; the mass concentration of peroxide in the surface decontamination sol is more than 0.1 and less than or equal to 40 percent; .

In some embodiments of the present invention, each mL of the surface decontamination sol contains 20-80 mg of oxygen-deficient titanium dioxide, and the mass concentration of the peroxide in the surface decontamination sol is 3%.

In some embodiments of the invention, the amount of excipient is selected to ensure that the surface-release sol has a consistency that does not readily flow when applied to the surface of the implant, that is maintained in the target area, and that does not contact and damage normal tissue.

Preferably, the mass concentration of the excipient in the surface decontamination sol is 0.5-9%, more preferably 2-4%.

In some embodiments of the invention, the peroxide comprises an inorganic peroxide or/and an organic peroxide; the inorganic peroxide is preferably hydrogen peroxide; the organic peroxide is preferably carbamide peroxide, peracetic acid, benzoyl peroxide, di-tert-butyl peroxide.

In some embodiments of the invention, the oxygen deficient titanium dioxide has oxygen vacancies and trivalent titanium ions.

The decontamination effect of the surface decontamination sol is realized based on three special effects of oxygen-deficient titanium dioxide and the synergistic enhancement effect of the three special effects. The three special effects include photocatalytic effect, Fenton-like effect and photothermal effect. The surface decontamination sol of the invention carries oxygen-deficient titanium dioxide through the excipient, endows the titanium dioxide with the adhesion capability on the titanium surface, constructs a red light/near infrared light controlled multifunctional nano platform, and the platform can closely and fully contact with the surface of an implant by virtue of the fluidity of the excipient, efficiently generates ROS and heat in situ on the polluted surface, effectively kills residual viable bacteria and disintegrates EPS.

The photocatalytic effect means that oxygen-deficient titanium dioxide generates photoproduction electrons and holes under the irradiation of red light/near infrared light, and organic matters adsorbed on the surface of the oxygen-deficient titanium dioxide can be thoroughly degraded.

The Fenton-like reaction means that oxygen-deficient titanium dioxide can catalyze hydrogen peroxide to be decomposed into hydroxyl radicals due to the existence of trivalent titanium ions with strong reducibility, and the catalytic reaction is slightly influenced by pH and does not produce secondary pollution. Meanwhile, the Fenton reaction is greatly influenced by temperature, and the catalytic effect on hydrogen peroxide is better along with the rise of the temperature in the range of 20-60 ℃.

The photothermal effect means that the oxygen-deficient titanium dioxide can convert light energy into heat energy under the irradiation of red light/near infrared light because the absorbance of the oxygen-deficient titanium dioxide is greatly improved in the spectral range of the wavelength of 400-2500nm compared with that of the common titanium dioxide.

The synergistic enhancement effect of the photocatalytic effect, the Fenton-like effect and the photothermal effect refers to that: 1) the oxygen-deficient titanium dioxide can catalyze peroxide to generate hydroxyl free radicals through two ways, including trivalent titanium ion catalysis and photoproduction electron catalysis, and the essence of the oxygen-deficient titanium dioxide is to provide electrons for the peroxide to break a peroxide bond of the peroxide to generate the free radicals; 2) the peroxide is activated by the oxygen-deficient titanium dioxide, and simultaneously, part of photo-generated electrons are effectively consumed, so that the recombination of photo-generated holes and electrons can be inhibited, and the photocatalysis is enhanced; 3) the oxygen-deficient titanium dioxide can convert light energy into heat energy while playing a role in photocatalysis under the activation of light, and the heat energy can greatly enhance Fenton-like reaction. In conclusion, the implant surface decontamination sol of the present invention is a synergistic system.

In addition, when the peroxide is hydrogen peroxide, the hydroxyl free radical generated after the peroxide is cracked can generate oxygen during quenching, the oxygen concentration around the oxygen-deficient titanium dioxide can be increased, the oxygen and the photo-generated electrons are combined to generate the superoxide anion free radical, more photo-generated electrons can be consumed to generate more superoxide anion free radicals, and the recombination of the photo-generated electrons and holes can be effectively inhibited.

In some embodiments of the invention, the excipient comprises sodium alginate and carbomer.

By adding the excipient, the oxygen-deficient titanium dioxide and the peroxide can be adhered to the surface of the implant to continuously work and can be conveniently removed.

In some embodiments of the invention, the alginate mass concentration in the surface decontamination sol is 2-4%, preferably 3%.

In some embodiments of the present invention, the light includes visible light and near infrared light, wherein the visible light band is 400-780nm, and the near infrared short band is 780-2500 nm; the visible light is preferably white light or monochromatic light, and the near-red light is preferably LED laser with the wavelength of 808 nm.

The light source of the light can be an LED lamp or a laser lamp.

The preparation method of the sol comprises the following steps:

step 1, preparing excipient sol: adding water into an excipient, and mixing to prepare excipient sol;

step 2, dispersing the defective titanium dioxide in water to prepare a suspension, adding the excipient sol prepared in the step 1, and uniformly mixing to obtain a working sol precursor;

and 3, uniformly mixing the peroxide solution and the working sol precursor to obtain the surface decontamination sol.

In some embodiments of the present invention, in the excipient sol prepared in step 1, the mass volume concentration of the excipient is 1-18 w/v%, wherein when the mass unit is g, the volume unit is mL;

in the suspension prepared in the step 2, the mass volume concentration of the oxygen-deficient titanium dioxide is 0.2-60 w/v%, wherein when the mass unit is g, the volume unit is mL;

in the step 3, the mass volume concentration of the peroxide solution is 0.2-40 w/v%, wherein when the mass unit is g, the volume unit is mL.

In some embodiments of the invention, in step 1, sodium alginate is mixed with water to prepare sodium alginate sol with a mass volume concentration (w/v) of 5% -7%, preferably 6%;

in some embodiments of the present invention, the water in step 2 is preferably deionized water; the concentration of the oxygen-deficient titanium dioxide in the suspension is 20-200mg/ml, preferably 80 mg/ml;

mixing the excipient sol and the oxygen-deficient titanium dioxide suspension according to the volume ratio of 10-1: 1;

the volume ratio of the working sol precursor to the peroxide solution is 2-15: 1, preferably in a volume ratio of 9: 1.

the application of the sol in the decontamination of the surface of an implant; preferably, the decontamination comprises sterilization or/and degradation of the biofilm; preferably the biofilm comprises extracellular matrix components secreted by bacteria, more preferably proteins, nucleic acids, polysaccharides macromolecules.

In some embodiments of the invention, the implant is an infected implant that is naturally exposed or surgically exposed.

The implant comprises a dental implant, a bone plate, a bone nail and an artificial joint; preferably, the material of the implant body includes titanium, titanium alloy, zirconium alloy, and polyether ether ketone (PEEK).

The application method of the light activated implant surface decontamination sol comprises the following steps: the surface of the implant body exposed naturally after infection or during surgical debridement is used after traditional mechanical scaling or irrigation treatment; coating the surface decontamination sol of the invention on the exposed surface of the implant; after coating, the coating plays a role under the activation of light, and is beneficial to removing EPS and killing residual viable bacteria along with the generation of heat and ROS.

The irradiation time is 1min-30min, the treatment time is adjusted according to the infection severity, and the treatment can be carried out for multiple times after the treatment is finished; the sol can be sucked away or washed clean by a negative pressure suction head.

The oxygen-deficient titanium dioxide of the present invention is prior art.

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

the invention has scientific design and simple and convenient operation, can effectively clean the surface of the implant, can not damage the surface of the implant, and has important significance for maintaining the coating on the surface of the implant. The invention endows the surface decontamination sol with excellent sterilization capability and degradation capability through 2 mild advanced oxidation technical principles, which is different from the traditional antibacterial sol (such as chlorhexidine sol) inactivation biomembrane.

In addition, the surface decontamination sol of the invention also has the function of enhancing the osteogenesis performance of the implant.

The invention has the advantages of easy acquisition of raw materials, low cost, mild sol synthesis conditions and convenient use.

Drawings

FIG. 1 is a flow chart of the preparation of the photoactivated implant surface decontamination sol of the present invention;

FIG. 2 is a graph showing the results of the antibacterial rate of the inventive photoactivated implant surface decontamination sol against Staphylococcus aureus plankton;

FIG. 3 is a graph showing the results of a Staphylococcus aureus resistant biofilm of the inventive photoactivated implant surface decontamination sol;

FIG. 4 is a graph of the results of degrading residual EPS of the photoactivated implant surface decontamination sol of the present invention;

FIG. 5 is a graph showing the results of experiments on the effect of promoting cell osteogenesis on the surface of an implant treated with the surface decontaminating sol of the present invention.

Detailed Description

The invention is described in further detail below with reference to the following figures and examples:

example 1

This example discloses a method for preparing the photoactivated implant surface decontamination sol of the present invention, and the preparation process is shown in fig. 1. The preparation method specifically comprises the following steps:

step 1, preparing excipient sol: taking a proper amount of sodium alginate, and dissolving the sodium alginate in deionized water under the action of magnetic stirring to form excipient sol with the mass concentration of 6% for later use;

step 2, dispersing a certain amount of oxygen-deficient titanium dioxide in deionized water, magnetically stirring uniformly at room temperature, and further dispersing by ultrasound to prepare 80mg/mL suspension for later use;

and 3, mixing the suspension prepared in the step 2 with the excipient sol prepared in the step 1 according to the volume ratio of 1:1, mixing, uniformly stirring at room temperature, performing ultrasonic treatment, standing, continuously stirring, performing ultrasonic treatment, and repeating the steps for 3 times to obtain a working sol precursor;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a hydrogen peroxide solution with the mass concentration of 30% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the two, pushing the working sol into one injector after the working sol is formed, taking down the screw injector connector, and connecting an injector needle to be used; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 9: 1.

example 2

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1, preparing excipient sol: taking a proper amount of carbomer, dissolving the carbomer in deionized water under the action of magnetic stirring, and adjusting the pH to 5-7 to form excipient sol with the mass concentration of 1% for later use;

step 2, dispersing a certain amount of oxygen-deficient titanium dioxide in deionized water, magnetically stirring uniformly at room temperature, and further dispersing by ultrasound to prepare 100mg/mL suspension for later use;

and 3, mixing the suspension prepared in the step 2 with the excipient sol prepared in the step 1 according to the volume ratio of 2: 1, mixing, uniformly stirring at room temperature, performing ultrasonic treatment, standing, continuously stirring, performing ultrasonic treatment, and repeating the steps for 3 times to obtain a working sol precursor;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a hydrogen peroxide solution with the mass concentration of 40% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the two, pushing the working sol into one injector after the working sol is formed, taking down the screw injector connector, and connecting an injector needle to be used; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 8: 1.

example 3

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1, preparing excipient sol: taking a proper amount of carbomer, dissolving the carbomer in deionized water under the action of magnetic stirring to form excipient sol with the mass concentration of 6% for later use;

step 2, dispersing a certain amount of oxygen-deficient titanium dioxide in deionized water, magnetically stirring uniformly at room temperature, and further dispersing by ultrasound to prepare 150mg/mL suspension for later use;

and 3, mixing the suspension prepared in the step 2 with the excipient sol prepared in the step 1 according to the volume ratio of 3: 2, mixing, uniformly stirring at room temperature, performing ultrasonic treatment, standing, continuously stirring, performing ultrasonic treatment, and repeating the steps for 3 times to obtain a working sol precursor;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a hydrogen peroxide solution with the mass concentration of 35% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the two, pushing the working sol into one injector after the working sol is formed, taking down the screw injector connector, and connecting an injector needle to use; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 7: 3.

example 4

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1, preparing excipient sol: taking a proper amount of sodium alginate, dissolving the sodium alginate in deionized water under the action of magnetic stirring to form excipient sol with mass concentration of 19% for later use;

step 2, dispersing a certain amount of oxygen-deficient titanium dioxide in deionized water, magnetically stirring uniformly at room temperature, and further dispersing by ultrasound to prepare a suspension of 20mg/mL for later use;

step 3. same as step 3 of example 1;

step 4. same as step 4 of example 1.

Example 5

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1, preparing excipient sol: taking a proper amount of carbomer and sodium alginate, dissolving the carbomer and the sodium alginate in deionized water under the action of magnetic stirring to form excipient sol with the mass concentration of both carbomer and sodium alginate being 5% for later use;

step 2, dispersing a certain amount of oxygen-deficient titanium dioxide in deionized water, magnetically stirring uniformly at room temperature, and further dispersing by ultrasound to prepare 200mg/mL suspension for later use;

step 3. same as step 3 of example 1;

step 4. same as step 4 of example 1.

Example 6

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1. same as step 1 of example 1;

step 2. same as step 2 of example 1;

step 3. same as step 3 of example 1;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a urea peroxide solution with the mass concentration of 30% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the two, pushing the working sol into one injector, taking down the screw injector connector, and connecting an injector needle to be used; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 9: 1.

example 7

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1. same as step 1 of example 1;

step 2. same as step 2 of example 1;

step 3. same as step 3 of example 1;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a urea peroxide solution with the mass concentration of 15% and a hydrogen peroxide solution with the mass concentration of 15% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the urea peroxide solution with the hydrogen peroxide solution to form the working sol, then pushing the working sol into one injector, taking down the screw injector connector, and connecting an injector needle to be used; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 9: 1.

example 8

The embodiment discloses a preparation method of the light-activated implant surface decontamination sol, which specifically comprises the following steps:

step 1. same as step 1 of example 1;

step 2. same as step 2 of example 1;

step 3. same as step 3 of example 1;

step 4, sucking the working sol precursor prepared in the step 3 into a screw injector, sucking a hydrogen peroxide solution with the mass concentration of 15% into another screw injector, connecting the two screw injectors through a screw injector connector, pushing the injectors back and forth to uniformly mix the two, pushing the working sol into one injector after the working sol is formed, taking down the screw injector connector, and connecting an injector needle to use; wherein the volume ratio of the working sol precursor to the hydrogen peroxide solution is 9: 1.

example 9

This example discloses the antimicrobial effect of the photoactivated implant surface decontamination sol of the present invention. In this embodiment, ATH is the surface decontamination sol prepared by the method of example 1, and AT is the working sol precursor prepared by the method of example 1; AH is a sol prepared by the method for preparing the decontamination sol of the surface of the implant according to the example 1 and without adding oxygen-deficient titanium dioxide; the A is the excipient sol prepared according to the method of the embodiment. The specific composition of ATH, AT, AH and A is as follows:

a: each 1ml of the product contains 3 percent of sodium alginate; (blank control group)

AH: each 1ml of the solution contains 3 percent of sodium alginate and 3 percent of hydrogen peroxide; (Hydrogen peroxide control group)

AT: every 1ml contains 3% sodium alginate and 40mg defective titanium dioxide; (defective titanium dioxide control group)

ATH: each 1ml contains 3% sodium alginate, 3% hydrogen peroxide and 40mg defective titanium dioxide. (Experimental group)

1. Staphylococcus plankton

Using a 96-well plate as a reaction vessel, 50. mu.L of ATH was added to 300. mu.L of the bacterial suspension (. apprxeq.1.5. about.10)⁸CFU/ml), mixing, and irradiating with light (0.505 wcm)^-2808nm) for 3min, and diluting the reacted bacterial liquid by 10⁵And coating 100 mu L of diluted bacterial liquid on an agar plate, putting the plate into an incubator at 37 ℃ for culturing for 12-20h, and photographing to count the viable bacteria. The results are shown in FIG. 2. It can be seen that the number of bacteria in the ATH group is minimal, confirming the excellent antibacterial effect of the ATH group. The light activated decontamination sol for the surface of the implant is proved to be effective in killing the staphylococcus plankton.

2 Staphylococcus aureus biofilm

Culturing Staphylococcus aureus biofilm on the surface of sand-blasting acid-etched titanium for 2 days, removing bacteria liquid after culturing, washing with physiological saline for three times to remove bacteria not adhered to the titanium surface, coating sol on the surface of titanium sheet, 1% CaCl₂The solution is fixed on the surface of the titanium sheet by crosslinking the surface layer of the composite sol, and the titanium sheet is irradiated by light (0.505 wcm) under the wet condition^-2808nm) for 15min, after the reaction is finished, washing the titanium surface by an oral three-way gun, dyeing the titanium sheet by a fluorescent dye for dying bacteria and performing semi-quantitative analysis, and the result is shown in the attached figure 3. FIG. 3 shows that ATH is superior to AH and AT AT the same hydrogen peroxide concentration when used against Staphylococcus aureus biofilms. The trend of the anti-biofilm results was consistent with that of planktonic bacteria in the ATH group, which was stronger than those in the AT group and AH group.

Example 10

This example discloses the degradation of biofilm by the photoactivated implant surface decontamination sol of the present invention and is similar to example 9.

1. Experiment for degrading biological film

Culturing Staphylococcus aureus on titanium sheet for two days to form a biofilm, treating the surface of the titanium sheet with carbon curette, coating ATH on the titanium sheet polluted by Staphylococcus aureus (2d) treated by the carbon curette, and adding 1% CaCl₂The solution is fixed on the surface of the titanium sheet by crosslinking the surface layer of the composite sol, and the solution is used for 0.505wcm under the wet condition^-2808nm near-red light for 15min, and oral cavity three-purpose waterThe gun removed the sol, the titanium plate was treated again under the same conditions, the obtained treated titanium plate was labeled with a fluorescent dye, and the amounts of nucleic acid, polysaccharide and protein were semi-quantitatively analyzed under a confocal laser microscope, and the results are shown in fig. 4. It is evident from fig. 4 that the pure group a still has a large amount of nucleic acids, polysaccharides, and proteins remaining on the surface even after scraping, light irradiation, and washing, which demonstrates that the conventional mechanical decontamination methods have limited decontamination capability, while the ATH group has better EPS degradation effect than the pure groups AH and AT.

Example 11

This example discloses experiments in which the inventive photoactivated implant surface decontamination sol promotes cell osteogenesis.

3 groups are set, firstly, a staphylococcus aureus biomembrane is cultured on a titanium sheet for 2 days, a carbon fiber curette is used for curettage, and the biomembrane which is not removed by curettage can simulate the clinical treatment of the biomembrane remained on the surface of the implant, and is named as residual biomembrane titanium sheet group (RB); the titanium sheet after scraping was subjected to sol light irradiation treatment (0.505 wcm)^-2808nm, 15min, 2 times), naming the sol to treat the titanium plate group (RB + ATH); clean SLA titanium sheets with uncultured biofilm were designated as clean titanium sheet set (No RB). The three groups of titanium sheets are sterilized by ethylene oxide, and then are co-cultured with bone marrow mesenchymal stem cells from rats of p3-p4 generation, ELISA is used for detecting the expression of Osteocalcin (OCN), Osteoprotegerin (OPG) and alkaline phosphatase (ALP) osteogenesis related proteins on the 7 th day of culture, alizarin red staining is used for detecting the formation condition of bone nodules on the 14 th day, 10% cetyl pyridine aqueous solution is used for extracting combined alizarin red dye, the absorbance is measured at 562nm after the dilution is doubled, and the osteogenesis condition is subjected to semi-quantitative analysis.

The results are shown in FIG. 5 and show that: the fact that the biological membrane remaining on the surface of the implant (inactivated) inhibits the osteogenic differentiation of rat mesenchymal stem cells proves its harmfulness.

Secondly, the titanium sheet group is treated by sol, the bone formation effect of the titanium sheet group is obviously improved compared with that of the titanium sheet group with the residual biomembrane, which shows that the residual biomembrane is effectively removed after the sol treatment.

The osteogenesis effect of the titanium sheet group treated by the sol is improved compared with that of a clean titanium sheet group, which shows that the sol has good biomembrane removing capability and can activate the titanium surface to ensure that the titanium sheet group has better osteogenesis activity.

The application method of the light activated implant surface decontamination sol comprises the following steps: the surface of the implant, which is exposed naturally after infection or when debrided by surgery, is used after traditional mechanical treatment; coating the surface decontamination sol of the invention on the exposed surface of the implant; after coating, the surface of the implant is irradiated by light with 400-780nm or/and 780-2500 nm. The irradiation time is 15-30 min.

The treatment time is properly increased according to the infection severity, and after the treatment is finished, the sol can be sucked away by using a negative pressure suction head.

Finally, it should be noted that: the above embodiments are only preferred embodiments of the present invention to illustrate the technical solutions of the present invention, but not to limit the technical solutions, and certainly not to limit the patent scope of the present invention; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention; that is, the technical problems to be solved by the present invention, which are not substantially changed or supplemented by the spirit and the concept of the main body of the present invention, are still consistent with the present invention and shall be included in the scope of the present invention; in addition, the technical scheme of the invention is directly or indirectly applied to other related technical fields, and the technical scheme is included in the patent protection scope of the invention.