Osteoclast nanoparticles for implant removal and preparation method and application thereof

By preparing and applying the bone-breaking nanoparticles MVs@Fe3O4@CoOx, combined with the magnetic guide device and the drug-carrying device, the minimally invasive, non-destructive and spatially controllable effects of implant removal are achieved, and the problems of complex removal and serious bone damage in the prior art are solved.

CN119838065BActive Publication Date: 2025-05-13STOMATOLOGICAL HOSPITAL OF SHANXI MEDICAL UNIVERSITY
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Patent Information

Application Number
CN202510336790.9
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-03-21
Publication Date
2025-05-13
Estimated Expiration
2045-03-21

AI Technical Summary

Technical Problem

The existing implant removal technology is complicated to operate, difficult to ensure prognostic results, and may lead to large-area bone defects, implant fragment residues and other complications.

Method used

The Fe3O4@CoOx nanoparticles were loaded into Porphyromonas gingivalis vesicles by preparation method, and the nanoparticles were loaded into the vesicles by ultrasonic resonance method to form MVs@Fe3O4@CoOx nanoparticles, and combined with a magnetic guide device and a drug-carrying device, the directional release of nanoparticles and bone binding damage on the implant surface were achieved.

Benefits of technology

At the microscopic level, the osteoclast function can be controlled spatially, destroy the combination of implants and bones, and achieve minimally invasive and non-destructive implant removal, reducing bone damage and laying the foundation for subsequent repair.

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Abstract

This invention belongs to the technical field of oral materials, and discloses osteoclast nanospheres for implant removal, their preparation method and application. A preparation method of osteoclast nanospheres for implant removal comprises the following steps: S1, prepare silica nanospheres; S2, deposit CoO x on the silica nanospheres to obtain SiO2@CoO x ; S3, etch SiO2@CoO x to obtain hollow mesoporous CoO x ; S4, deposit Fe3O4 on the hollow mesoporous CoO x to obtain Fe3O4@CoO x nanospheres; S5, obtain Porphyromonas gingivalis vesicles; S6, load the Fe3O4@CoO x nanospheres into the Porphyromonas gingivalis vesicles by ultrasonic resonance method. This invention can regulate the function of osteoclasts at the microscopic level to destroy the bond between the implant and the bone.
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Description

Technical Field

[0001] The invention belongs to the technical field of oral materials, and in particular relates to a bone-crushing nanoparticle for implant removal, and a preparation method and application thereof. Background Art

[0002] Denture implants have become a reliable option for patients with edentulous or missing teeth to rebuild teeth and restore chewing function. The biological basis of implants is that bone cells and titanium surfaces are biologically integrated after implant placement. However, after 5 to 10 years of use, 12% of implants will experience fractures, adjustment of the repair plan, infection, aesthetics, and pain, and the implants that have completed the biological integration with the bone need to be removed from the bone.

[0003] At present, the implant removal techniques for forming bone integration include anti-torque ratchet wrench, reverse thread technology, ultrasonic bone knife, high-speed needle, tooth collar, dental forceps and trephine. The principle of anti-torque ratchet wrench and reverse thread technology is to use the force in the opposite direction of implant insertion to screw out the implant, and directly destroy the bone integration on the implant surface by violence. These two methods are prone to secondary fractures, and the remaining fractured pieces are more difficult to remove; violent removal may even cause alveolar process and even jaw fractures. Ultrasonic bone knife, high-speed needle, tooth collar, dental forceps and trephine are schemes that directly remove a large amount of alveolar bone around the implant. After the implant is removed, it is often seen that there is still a large amount of bone on the implant surface. It belongs to a destructive removal scheme, and the large area of ​​bone defect caused by destructive removal will inevitably make it difficult for patients to implant again in the future. At the same time, the application of the above-mentioned implant removal techniques for bone-integrated implant removal may also lead to complications such as residual implant fragments, instrument breakage, and violent accidental injury. In summary, the implant removal technology commonly used in clinical practice is complicated to operate, and it is difficult to guarantee the prognosis and lay a good foundation for subsequent implant restoration. There is an urgent need to explore more sophisticated, minimally invasive, and directionally controllable implant removal devices and technologies. Summary of the invention

[0004] The purpose of the present invention is to provide a osteoclast nanoparticle for implant removal and a preparation method and application thereof, so as to solve the problem mentioned in the background technology that the current commonly used implant removal technology in clinical practice is complicated to operate, difficult to ensure the prognosis and lay a good foundation for subsequent implant restoration.

[0005] To achieve the above object, the present invention provides a method for preparing osteoclast nanoparticles for implant removal, comprising the following steps:

[0006] S1, preparing silica nanospheres;

[0007] S2, CoO x Deposited on silica nanospheres to obtain SiO2@CoO x ;

[0008] S3, SiO2@CoO x Etching reaction treatment was performed to obtain hollow mesoporous CoO x ;

[0009] S4, deposit Fe3O4 in hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles;

[0010] S5, obtaining Porphyromonas gingivalis vesicles;

[0011] S6. Fe3O4@CoO was prepared by ultrasonic resonance method. x Nanoparticles were loaded into Porphyromonas gingivalis vesicles to obtain MVs@Fe3O4@CoO x .

[0012] In a specific embodiment, in step S1, the specific steps of preparing silica nanospheres are:

[0013] After tetraethyl orthosilicate aqueous solution, deionized water and ammonia solution are mixed and stirred, the generated SiO2 precipitate is separated by centrifugation, and the white SiO2 precipitate obtained by washing and centrifugation is washed with deionized water and anhydrous ethanol respectively, collected and dried to obtain silica nanospheres.

[0014] In a specific embodiment, in step S1, the stirring time is 22-26 hours, the centrifugal speed during centrifugal separation is 12000 rpm, the centrifugal time is 10 minutes, and the white SiO2 precipitate is washed three times with deionized water and anhydrous ethanol respectively.

[0015] In a specific implementation, the specific steps of step S2 are:

[0016] The silicon dioxide nanospheres are transferred to the ALD reactor; cobalt cyclopentadienyl and O3 are introduced into the ALD reactor as precursors to make CoO x Deposited on air-dried silica nanospheres to obtain SiO2@CoO x .

[0017] In a specific embodiment, in step S2, before introducing cobaltocene and O3 into the ALD reactor, the silica nanospheres prepared in step S1 are first dispersed in ethanol and subjected to ultrasonic treatment; the silica nanospheres are then air-dried; and after being completely dried, the air-dried silica nanospheres are transferred to the ALD reactor;

[0018] In a specific embodiment, the deposition temperature of the ALD reactor is set to 220°C; before being introduced into the reactor, the cobaltocene precursor is first heated to 80°C; during the reaction of the ALD reactor, the cobaltocene and O3 are both introduced into the ALD reactor in a pulsed form, and the carrier gas used is N2.

[0019] In a specific implementation, the specific steps of step S3 are:

[0020] The obtained SiO2@CoO x After calcination, the particles were dispersed in deionized water and ultrasonically treated; then the treated SiO2@CoO x The particles were evenly dispersed in a sodium hydroxide solution, and the etching reaction was carried out at 70°C for 10-14 hours, followed by centrifugation. The white precipitate was collected and washed three times with deionized water and anhydrous ethanol, and then collected and dried. x After annealing at 400 °C in air, hollow mesoporous CoO x .

[0021] In a specific implementation, the specific steps of step S4 are:

[0022] First, the prepared hollow mesoporous CoO x The Fe3O4 was dispersed in ethanol, air-dried after ultrasonic treatment, and transferred to the ALD reactor after complete drying. Ferrocene and O3 were introduced into the ALD reactor as precursors to deposit Fe3O4 in the hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles.

[0023] The present invention also provides an osteoclast nanoparticle for implant removal, and the prepared MVs@Fe3O4@CoO x .

[0024] The present invention also provides a device for removing an implant, comprising a magnetic guide device and a drug carrying device, wherein the magnetic guide device is in the shape of a screw, with an external thread matching the internal thread inside the implant arranged on the side, a magnet arranged at the tip of the bottom, and a top fixedly connected to the drug carrying device;

[0025] The drug-carrying device includes a drug-carrying box body, a collagen membrane, and osteoclast nanoparticles for implant removal as described above, which are arranged inside the drug-carrying box body; the drug-carrying box body is in the shape of a regular prism with a hollow interior and an open lower end, a collagen membrane is arranged at the lower opening of the drug-carrying box body, the top of the magnetic guide device passes through the collagen membrane and is fixedly connected to the drug-carrying box body, and the collagen membrane is used to seal the osteoclast nanoparticles.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The osteoclast nanoparticles of the present invention can spatially controllably regulate the function of osteoclasts at a microscopic level to destroy the combination of implants and bones.

[0028] The present invention is a spatially controllable ring implant osteoclast nanoparticle. After the overall structure is installed inside the implant, MVs@Fe3O4@CoO x The nanoparticles begin to be released and move directionally along the surface of the implant, inducing osteoclast differentiation, destroying the bone integration on the implant surface, reducing the resistance to implant rotation, and ultimately achieving the effect of minimally invasive and non-destructive implant removal.

[0029] In addition to the above-described objects, features and advantages, the present invention has other objects, features and advantages. The present invention is further described in detail below. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The drawings constituting a part of this application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0031] Figure 1 It is a flow chart of a method for preparing osteoclast nanoparticles for implant extraction according to the present invention;

[0032] Figure 2 This is a SEM image of a bone-crushing nanoparticle used for implant extraction according to the present invention;

[0033] Figure 3 This is an EDS image of a bone-crushing nanoparticle used for implant extraction according to the present invention;

[0034] Figure 4 is a cross-sectional schematic diagram of a device for removing an implant according to the present invention;

[0035] Among them, 1. Magnetic guiding device; 2. Drug-carrying box; 3. Collagen membrane; 4. Osteoclast nanoparticles. DETAILED DESCRIPTION

[0036] The embodiments of the present invention are described in detail below. The specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0037] The present invention provides a method for preparing osteoclast nanoparticles for implant removal, comprising the following steps:

[0038] S1, preparing silica nanospheres;

[0039] In step S1, the specific steps of preparing silicon dioxide nanospheres are:

[0040] After tetraethyl orthosilicate aqueous solution, deionized water and ammonia solution are mixed and stirred, the generated SiO2 precipitate is separated by centrifugation, and the white SiO2 precipitate obtained by washing and centrifugation is washed with deionized water and anhydrous ethanol respectively, collected and dried to obtain silica nanospheres.

[0041] In the step S1, the stirring time is 22-26 hours, the centrifugal speed during centrifugal separation is 12000 rpm, the centrifugal time is 10 minutes, and the white SiO2 precipitate is washed three times with deionized water and anhydrous ethanol respectively.

[0042] S2, CoO x Deposited on silica nanospheres to obtain SiO2@CoO x ;

[0043] The specific steps of step S2 are:

[0044] The silicon dioxide nanospheres are transferred to the ALD reactor; cobalt cyclopentadienyl and O3 are introduced into the ALD reactor as precursors to make CoO x Deposited on air-dried silica nanospheres to obtain SiO2@CoO x .

[0045] In the step S2, before introducing the cobaltocene and O3 into the ALD reactor, the silica nanospheres prepared in the step S1 are first dispersed in ethanol and subjected to ultrasonic treatment; the silica nanospheres are then air-dried; and after being completely dried, the air-dried silica nanospheres are transferred to the ALD reactor;

[0046] The deposition temperature of the ALD reactor is set at 220°C. Before being introduced into the reactor, the cobaltocene precursor is first heated to 80°C. During the reaction process of the ALD reactor, cobaltocene and O3 are introduced into the ALD reactor in pulse form, and the carrier gas used is N2.

[0047] S3, SiO2@CoO x Etching reaction treatment was performed to obtain hollow mesoporous CoO x ;

[0048] The specific steps of step S3 are:

[0049] The obtained SiO2@CoO x After calcination, the particles were dispersed in deionized water and ultrasonically treated; then the treated SiO2@CoO xThe particles were evenly dispersed in a sodium hydroxide solution, and the etching reaction was carried out at 70°C for 10-14 hours, followed by centrifugation. The white precipitate was collected and washed three times with deionized water and anhydrous ethanol, and then collected and dried. x After annealing at 400 °C in air, hollow mesoporous CoO x .

[0050] S4, deposit Fe3O4 in hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles;

[0051] The specific steps of step S4 are:

[0052] First, the prepared hollow mesoporous CoO x The Fe3O4 was dispersed in ethanol, air-dried after ultrasonic treatment, and transferred to the ALD reactor after complete drying. Ferrocene and O3 were introduced into the ALD reactor as precursors to deposit Fe3O4 in the hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles.

[0053] S5, obtaining Porphyromonas gingivalis vesicles;

[0054] S6. Fe3O4@CoO was prepared by ultrasonic resonance method. x Nanoparticles were loaded into Porphyromonas gingivalis vesicles to obtain MVs@Fe3O4@CoO x .

[0055] The present invention also provides an osteoclast nanoparticle for implant removal, and the prepared MVs@Fe3O4@CoO x .

[0056] The present invention also provides a device for removing an implant, comprising a magnetic guide device and a drug carrying device, wherein the magnetic guide device is in the shape of a screw, with an external thread matching the internal thread inside the implant arranged on the side, a magnet arranged at the tip of the bottom, and a top fixedly connected to the drug carrying device;

[0057] The drug-carrying device includes a drug-carrying box body 2, a collagen membrane 3, and osteoclast nanoparticles 4 for implant removal as described above, which are arranged inside the drug-carrying box body; the drug-carrying box body 2 is in the shape of a regular prism with a hollow interior and an open lower end, and a collagen membrane 3 is arranged at the lower end opening of the drug-carrying box body 2. The top of the magnetic guide device 1 passes through the collagen membrane 3 and is fixedly connected to the drug-carrying box body 2, and the collagen membrane 3 is used to seal the osteoclast nanoparticles 4.

[0058] Example 1

[0059] The present invention provides a method for preparing osteoclast nanoparticles for implant removal, comprising the following steps:

[0060] S1, preparing silica nanospheres;

[0061] Mix 1.7 mL of 0.1-0.5 mol / L tetraethyl orthosilicate aqueous solution, 0.8 mL of deionized water and 1.7 mL of 28 wt.% ammonia aqueous solution, and stir vigorously for 24 h. Centrifuge the resulting SiO2 precipitate at 12000 rpm for 10 min. Wash the white SiO2 precipitate obtained by washing and centrifugation three times with deionized water and anhydrous ethanol, respectively, and then collect and dry for later use.

[0062] S2, CoO x Deposited on silica nanospheres to obtain SiO2@CoO x ;

[0063] First, the prepared SiO2 nanospheres were dispersed in ethanol and ultrasonicated for 20 min. Then, the SiO2 nanospheres were dropped on a quartz wafer for air drying and, after being completely dried, were transferred to the ALD reactor. x , a certain number of cycles of cobaltocene and O3 pulses are alternately introduced into the reactor. ALD deposition of CoO x The reaction parameters are as follows: the deposition temperature is 220°C, and cobaltocene and O3 are the precursors used. Before being introduced into the reactor, the cobaltocene precursor is heated to 80°C to reach a vapor pressure that can support the reaction. The carrier gas used in the reaction process consists of 50 sccm of high-purity nitrogen (N2). In each cycle, the pulse time of cobaltocene is 5.5s, the holding time is 16s, and the blowing time of N2 is 25s; the pulse time of O3 is 0.10 s, the holding time is 12s, and the blowing time of N2 is 25s. For convenience, the CoO produced by ALD is x The samples were labeled as SiO2@mCoO x , where m is CoO x The number of deposition cycles: m is at least greater than 20 times, preferably m is 50 to 150 times, and more preferably m is 100 times.

[0064] S3, SiO2@CoO x Etching reaction treatment was performed to obtain hollow mesoporous CoO x ;

[0065] 0.1g of SiO2@CoO xThe particles were dispersed in 20 mL of deionized water and ultrasonically treated for 60 min. x The particles were evenly dispersed in 20 mL of 2 mol / L sodium hydroxide solution, and the etching reaction was carried out at 70 ° C for 12 h and then centrifuged. The white precipitate after centrifugation was collected and washed three times with deionized water and anhydrous ethanol, and then collected and dried. x Annealing at 400 °C in air atmosphere to obtain hollow mesoporous CoO with high crystallinity x .

[0066] S4, deposit Fe3O4 in hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles;

[0067] First, the prepared hollow mesoporous CoO x The nanospheres were dispersed in ethanol and ultrasonicated for 20 min. x The nanospheres were dropped onto a quartz wafer and air-dried. After the sample was completely dried, the material was transferred to the ALD reactor. To deposit Fe3O4, pulses of ferrocene and O3 with different numbers of cycles were alternately introduced into the reactor. The reaction parameters for the ALD deposition of Fe3O4 were as follows: the deposition temperature was 200°C, and ferrocene and O3 were the precursors used. Before being introduced into the reactor, the ferrocene precursor was heated to 80°C to reach a vapor pressure that could support the reaction. The carrier gas used during the reaction consisted of 50 sccm of high-purity nitrogen (N2). The pulse time of ferrocene was 5.5s, the holding time was 16s, and the blowing time of N2 was 25s. The pulse time of O3 was 0.10s, the holding time was 12s, and the blowing time of N2 was 25s.

[0068] S5, obtaining Porphyromonas gingivalis vesicles;

[0069] The conditioned medium containing P. gingivalis was centrifuged at 300 × g for 10 min to remove any cells or large cell debris. The supernatant was then collected and transferred to an ultracentrifuge tube. The sample was centrifuged at 16,500 × g for 20 min to remove microvesicles. The supernatant was carefully collected and centrifuged at 120,000 × g for 2.5 h at 4 °C. The vesicle pellet was reconstituted in PBS and stored at -80 °C.

[0070] S6. Fe3O4@CoO was prepared by ultrasonic resonance method. x Nanoparticles were loaded into Porphyromonas gingivalis vesicles to obtain MVs@Fe3O4@CoO x .

[0071] Fe3O4@CoO xThe nanoparticles were placed in PBS, and the mixture was sonicated using an ultrasonic probe at 20% amplitude for 6 cycles, each cycle lasting 3 minutes, covering 6 30-second on / off cycles, with a 2-minute cooling period between each cycle, to prepare MVs@Fe3O4@CoO x .

[0072] The present invention also provides a device for removing an implant, comprising a magnetic guiding device and a drug carrying device.

[0073] The magnetic guide device is in the shape of a screw, with an external thread matching the internal thread inside the implant on the side, which is used to be screwed into the implant, and a magnet is installed at the bottom tip to guide the MVs@Fe3O4@CoO x The nanoparticles move along the surface of the implant without spreading around. The top is fixedly connected to the drug-carrying device. Preferably, the length of the magnetic guide device reaches two-thirds of the entire implant after being screwed into the implant.

[0074] The drug-carrying device comprises a drug-carrying box body 2, a collagen membrane 3 and the osteoclast nanoparticles 4 for implant removal as described above, which are arranged inside the drug-carrying box body; the drug-carrying box body 2 is in the shape of a regular prism with a hollow interior and an open lower end, and a collagen membrane 3 is arranged at the lower opening of the drug-carrying box body 2. The top of the magnetic guide device 1 passes through the collagen membrane 3 and is fixedly connected to the drug-carrying box body 2. The collagen membrane 3 is used to seal the osteoclast nanoparticles 4. The collagen membrane 3 is used to contact the implant. When the collagen membrane 3 contacts the implant, the collagen membrane 3 is damaged and begins to release MVs@Fe3O4@CoO x Nanoparticles.

[0075] The existing technical solutions all focus on destroying bone bonding at the macro level. The MVs@Fe3O4@CoOx nanoparticles provided by the present invention can spatially control the function of osteoclasts to destroy the bonding between implants and bones at the micro level. The particles are made of superparamagnetic nanoparticles Fe3O4 deposited on CoOx nanospheres by atomic layer deposition, and then Fe3O4@CoO x Nanoparticles were encapsulated into Porphyromonas gingivalis vesicles (MVs). MVs@Fe3O4@CoO x The nanoparticles first contacted the attached gingiva around the implant. The MVs located at the outermost part of the nanoparticles specifically degraded the gingival epithelial cell junction adhesion molecules after contacting the attached gingiva, increasing the permeability of the gingival epithelium. x The nanoparticles can smoothly pass through the gingival epithelium and expose Fe3O4 located in the middle layer.

[0076] Fe in Fe3O4 2+On the one hand, it produces highly active ROS through the Fenton reaction, and on the other hand, it participates in the generation of ROS by affecting the activity of various enzymes and the function of mitochondria, thereby inducing osteoclast differentiation and activating osteoclasts to destroy bone bonding, thereby achieving the purpose of loosening the implant. 2+ Reaction occurs to expose internal CoO x After that, CoO x In a neutral environment, it activates superoxide dismutase (SOD) and catalase (CAT) to effectively remove excessively accumulated ROS in the bone tissue around the implant, thereby reducing the activation of osteoclasts and limiting them to the implant surface, preventing a wider range of bone tissue loss.

[0077] The spatial control device provided by the present invention for loading nanoparticles for inducing osteoclast differentiation and action around implants is divided into two parts: a magnetic guide device and a drug loading device. The surface of the magnetic guide device is provided with threads that can match the internal threads of the implant and penetrate into the implant. The front end of the magnetic guide device is provided with a strong magnet to release the magnetic field. The drug loading device is fixedly connected to the magnetic guide device, and is loaded with nanoparticles for breaking the bone bond on the surface of the implant. The diameter of the drug loading device is wider than the external diameter of the implant, and the edge of the implant is wrapped to form a structure similar to a bottle cap. A collagen membrane 3 is provided at the part in contact with the external threads of the implant to store the nanoparticles. When the collagen membrane 3 contacts the implant, the collagen membrane 3 is broken to release the nanoparticles.

[0078] MVs@Fe3O4@CoO x After the nanoparticles are released from the collagen membrane 3 of the drug-carrying device, the magnetic field of the magnetic guide device causes the MVs@Fe3O4@CoO x The implant surface corresponding to the end of the magnetic guide device moves slowly along the external thread surface of the implant and limits its diffusion to the surroundings. x When the magnetic guide device reaches the implant surface at a horizontal position at the end thereof, the device stops moving and is continuously adsorbed to the implant surface under the action of magnetic force.

[0079] Since the length of the magnetic guide device reaches two-thirds of the entire implant after being screwed into the implant, the bone bonding on the implant surface is at MVs@Fe3O4@CoO x More than 2 / 3 of the implant has been destroyed by the nanoparticles, and the remaining bone bonding cannot maintain the stability of the implant and begins to loosen. At this time, the clinician can remove the implant and the device of the present invention together with ordinary instruments. When removing the implant, the remaining MVs@Fe3O4@CoOx Nanoparticles adsorbed on the implant surface are removed together, which can avoid the nanoparticles remaining in the implant cavity, and ultimately achieve the purpose of precise, minimally invasive and time-space controllable bone-integrated implant removal.

[0080] The above contents are further detailed descriptions of the present invention in combination with specific preferred embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several simple deductions and substitutions can be made without departing from the concept of the present invention, which should be regarded as belonging to the protection scope of the present invention.

Claims

1. A method for preparing osteoclast nanoparticles for implant removal, characterized in that: The steps include: S1, preparing silica nanospheres; S2, CoO x Deposited on silica nanospheres to obtain SiO2@CoO x ; S3, SiO2@CoO x Etching reaction treatment was performed to obtain hollow mesoporous CoO x ; S4, deposit Fe3O4 in hollow mesoporous CoO x On the surface, Fe3O4@CoO x Nanoparticles; S5, obtaining Porphyromonas gingivalis vesicles; S6. Fe3O4@CoO was prepared by ultrasonic resonance method. x Nanoparticles were loaded into Porphyromonas gingivalis vesicles to obtain MVs@Fe3O4@CoO x .

2. The method for preparing osteoclast nanoparticles for implant removal according to claim 1, characterized in that: In step S1, the specific steps of preparing silicon dioxide nanospheres are: After tetraethyl orthosilicate aqueous solution, deionized water and ammonia solution are mixed and stirred, the generated SiO2 precipitate is separated by centrifugation, and the white SiO2 precipitate obtained by washing and centrifugation is washed with deionized water and anhydrous ethanol respectively, collected and dried to obtain silica nanospheres.

3. The method for preparing osteoclast nanoparticles for implant removal according to claim 2, characterized in that: In the step S1, the stirring time is 22-26 hours, the centrifugal speed during centrifugal separation is 12000 rpm, the centrifugal time is 10 minutes, and the white SiO2 precipitate is washed three times with deionized water and anhydrous ethanol respectively.

4. The method for preparing osteoclast nanoparticles for implant removal according to claim 1, characterized in that: The specific steps of step S2 are: The silicon dioxide nanospheres are transferred to the ALD reactor; cobalt cyclopentadienyl and O3 are introduced into the ALD reactor as precursors to make CoO x Deposited on air-dried silica nanospheres to obtain SiO2@CoO x .

5. The method for preparing osteoclast nanoparticles for implant removal according to claim 4, characterized in that: In the step S2, before introducing cobaltocene and O3 into the ALD reactor, the silica nanospheres prepared in step S1 are first dispersed in ethanol and ultrasonically treated; the silica nanospheres are then air-dried; and after being completely dried, the air-dried silica nanospheres are transferred to the ALD reactor.

6. The method for preparing osteoclast nanoparticles for implant removal according to claim 4, characterized in that: The deposition temperature of the ALD reactor is set at 220°C. Before being introduced into the reactor, the cobaltocene precursor is first heated to 80°C. During the reaction process of the ALD reactor, cobaltocene and O3 are introduced into the ALD reactor in pulse form, and the carrier gas used is N2.

7. The method for preparing osteoclast nanoparticles for implant removal according to claim 1, characterized in that: The specific steps of step S3 are: The obtained SiO2@CoO x After calcination, the particles were dispersed in deionized water and ultrasonically treated; then the treated SiO2@CoO x The particles were evenly dispersed in a sodium hydroxide solution, and the etching reaction was carried out at 70°C for 10-14 hours, followed by centrifugation. The white precipitate was collected and washed three times with deionized water and anhydrous ethanol, and then collected and dried. x After annealing at 400 °C in air, hollow mesoporous CoO x .

8. The method for preparing osteoclast nanoparticles for implant removal according to claim 1, characterized in that: The specific steps of step S4 are: First, the prepared hollow mesoporous CoO x The Fe3O4 was dispersed in ethanol, air-dried after ultrasonic treatment, and transferred to the ALD reactor after complete drying. Ferrocene and O3 were introduced into the ALD reactor as precursors to deposit Fe3O4 in the hollow mesoporous CoO x On the surface, Fe3O4@CoOx nanoparticles were obtained.

9. An osteoclastogenic nanoparticle for implant removal, characterized in that: The MVs@Fe3O4@CoO prepared by the method for preparing osteoclast nanoparticles for implant removal as described in any one of claims 1 to 8 is x .

10. A device for removing an implant, characterized in that: It comprises a magnetic guide device (1) and a drug carrying device, wherein the magnetic guide device is in the shape of a screw, with an external thread matching the internal thread inside the implant being arranged on the side, a magnet being arranged at the tip of the bottom, and the top being fixedly connected to the drug carrying device; The drug-carrying device comprises a drug-carrying box body (2), a collagen membrane (3), and osteoclast nanoparticles (4) for implant extraction as claimed in claim 9 arranged inside the drug-carrying box body; the drug-carrying box body (2) is in the shape of a regular prism with a hollow interior and an open lower end, the collagen membrane (3) is arranged at the lower opening of the drug-carrying box body (2), the top of the magnetic guide device (1) passes through the collagen membrane (3) and is fixedly connected to the drug-carrying box body (2), and the collagen membrane (3) is used to seal the osteoclast nanoparticles (4).

Citation Information

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