[go: up one dir, main page]

WO2016171310A1 - Procédé de fabrication d'implant dentaire chargé de médicament - Google Patents

Procédé de fabrication d'implant dentaire chargé de médicament Download PDF

Info

Publication number
WO2016171310A1
WO2016171310A1 PCT/KR2015/005275 KR2015005275W WO2016171310A1 WO 2016171310 A1 WO2016171310 A1 WO 2016171310A1 KR 2015005275 W KR2015005275 W KR 2015005275W WO 2016171310 A1 WO2016171310 A1 WO 2016171310A1
Authority
WO
WIPO (PCT)
Prior art keywords
tio
nanotube array
anodization
drug
titanium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2015/005275
Other languages
English (en)
Korean (ko)
Inventor
최원열
이재관
장인산
최동순
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Industry Academy Cooperation Foundation of Gangneung Wonju National University
Original Assignee
Industry Academy Cooperation Foundation of Gangneung Wonju National University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Industry Academy Cooperation Foundation of Gangneung Wonju National University filed Critical Industry Academy Cooperation Foundation of Gangneung Wonju National University
Publication of WO2016171310A1 publication Critical patent/WO2016171310A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C13/00—Dental prostheses; Making same
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations

Definitions

  • the present invention relates to a method for manufacturing a dental implant loaded with drugs, and more particularly to a method for manufacturing a dental implant having a high bone to implant contact ratio (BIC) and bone volume ratio (bone volume ratio).
  • BIC bone to implant contact ratio
  • bone volume ratio bone volume ratio
  • micron ( ⁇ m) sized pores are formed in the implant using manufacturing processes such as sand blaster, wet etching, and anodizing. There is an attempt.
  • manufacturing processes such as sand blaster, wet etching, and anodizing.
  • titanium anodizing have not yet been precisely identified, and several research teams have recently studied the mechanisms.
  • Micrometer-sized pores have been reported to enhance mechanical adhesion that prevents implanted implants from detaching and enhance bone bond strength because they form a friendly surface with osteoblasts.
  • the problem to be solved by the present invention is to provide a method for producing a dental implant having a high BIC (bone to implant contact ratio) and bone volume ratio (bone volume ratio).
  • the present invention by using the electrolytic solution containing fluorine (F) in the first oxide cathode of titanium metal or titanium alloy formed on the surface of the step, and the titanium metal or titanium alloy to form the TiO 2 nanotube array TiO 2 and removing sonicated nanotube array, the TiO 2 nanotube array against a titanium metal or titanium alloy of the removed surface of the second oxide cathode using an electrolyte solution containing fluorine (F) TiO 2 nano-tubes Forming an array and loading the drug into the TiO 2 nanotube array formed by the second anodization provides a method of manufacturing a dental implant loaded with the drug.
  • the TiO 2 nanotube array formed by the second anodization has a tubular structure in which the upper portion is open and the lower portion is closed, and the inner diameter is preferably 10 to 300 nm.
  • the drug may include at least one substance selected from recombinant human bone morphogenetic protein-2 (rhBMP-2) and an anti-inflammatory agent.
  • rhBMP-2 recombinant human bone morphogenetic protein-2
  • an anti-inflammatory agent rhBMP-2
  • the electrolyte solution is sulfuric acid (H 2 SO 4 ), phosphoric acid (H 3 PO 4 ), citric acid (citric acid), oxalic acid (oxalic acid), ethylene glycol (Ethylene Glycol), glycerol (Glycerol), dimethyl sulfoxide (Dimethyl Sulfoxide; DMSO) may be a solution mixed with NH 4 F to one or more solutions selected from.
  • the first anodization or the second anodization is to place a positive electrode and a negative electrode in which the titanium metal or titanium alloy is disposed apart from each other, so that the positive electrode and the negative electrode is contained in the electrolyte in the electrolytic cell containing the electrolyte,
  • the voltage is applied to the cathode, and the voltage applied to form the TiO 2 nanotube array formed by the first anodization or the second anodization is applied so that the voltage difference between the anode and the cathode is less than or equal to 80V. It is desirable to.
  • drugs such as Recombinant human bone morphogenetic protein-2 (rhBMP-2), anti-inflammatory agents, and the like can be inserted.
  • the drug-loaded implant prepared according to the present invention has a high BIC (bone to implant contact ratio) and bone volume ratio.
  • 1 is a schematic structural diagram of equipment for performing for anodizing process.
  • Figure 2 is a schematic diagram showing the configuration of the device to observe by interferometric biosensing method for TiO 2 nanotube array.
  • 3A and 3B show a typical image and microstructure of a titanium implant as a processing implant.
  • 4A and 4B show rough surface images and microstructures of sandblasted large-grit and acid-etched (SLA) implants.
  • 5A and 5B show rough surfaces of TiO 2 nanotube arrays produced by anodization.
  • Figure 6a to Figure 6d is a diagram showing the TiO 2 nanotube array FESEM image of the surface and TiO 2 nano-tube array is loaded in the rhBMP-2.
  • 7 is a graph showing the change in optical thickness for 10 days according to rhBMP-2 loading.
  • 9 to 12 show four groups of fluorescence and histologic staining images observed with an optical microscope.
  • nano is used to mean a size in the range of 1 nm to 1 [mu] m as a size in nanometers, and the nanotubes have a tubular structure and mean that the inner diameter is nano.
  • a TiO 2 nanotube array is formed by first anodizing a titanium metal or a titanium alloy using an electrolyte solution containing fluorine (F). And removing the TiO 2 nanotube array formed on the surface of the titanium metal or titanium alloy by sonicating the fluorine (F) with respect to the titanium metal or titanium alloy on which the TiO 2 nanotube array is removed.
  • the TiO 2 nanotube array formed by the second anodization has a tubular structure in which the upper portion is open and the lower portion is closed, and the inner diameter is preferably 10 to 300 nm.
  • the drug may include at least one substance selected from recombinant human bone morphogenetic protein-2 (rhBMP-2) and an anti-inflammatory agent.
  • rhBMP-2 recombinant human bone morphogenetic protein-2
  • an anti-inflammatory agent rhBMP-2
  • the electrolyte solution is sulfuric acid (H 2 SO 4 ), phosphoric acid (H 3 PO 4 ), citric acid (citric acid), oxalic acid (oxalic acid), ethylene glycol (Ethylene Glycol), glycerol (Glycerol), dimethyl sulfoxide (Dimethyl Sulfoxide; DMSO) may be a solution mixed with NH 4 F to one or more solutions selected from.
  • the first anodization or the second anodization is to place a positive electrode and a negative electrode in which the titanium metal or titanium alloy is disposed apart from each other, so that the positive electrode and the negative electrode is contained in the electrolyte in the electrolytic cell containing the electrolyte,
  • the voltage is applied to the cathode, and the voltage applied to form the TiO 2 nanotube array formed by the first anodization or the second anodization is applied so that the voltage difference between the anode and the cathode is less than or equal to 80V. It is desirable to.
  • TiO 2 nanotube arrays are formed by first anodizing a titanium metal or a titanium alloy using an electrolyte solution containing fluorine (F).
  • the anode and the cathode on which the titanium metal or the titanium alloy is disposed are spaced apart from each other. To perform.
  • the material for the first anodization may be titanium (Ti) or titanium (Ti) alloy.
  • the titanium (Ti) alloy is an alloy including at least a titanium (Ti) component, such as a Ti-6Al-4V alloy.
  • Titanium and titanium alloys are widely used in the field of dental implants because of their excellent mechanical properties and biocompatibility.
  • the native oxide layer of titanium can bind directly to bone in the early stages of osteointegration.
  • Implant surface chemistry by methods such as blasting, plasma spraying of hydroxyapatite, sandblasting, etching, and anodic oxidation
  • the anodization equipment includes an electrochemical bath 10, an electrolyte 20, an anode 30, a cathode 40, a power supply 50, and a magnetic stirrer. 80, a stirring magnetic rod 90, a chiller 85, a thermometer 95 and the like.
  • the anode 30 and the cathode 40 are spaced apart from each other at a predetermined distance.
  • the anode 30 uses titanium (Ti) or a titanium alloy, which is the same as the metal component of the TiO 2 nanotube array to be obtained.
  • the electrolyte for the first anodic oxidation is sulfuric acid (H 2 SO 4 ), phosphoric acid (H 3 PO 4 ), citric acid (citric acid), oxalic acid, ethylene glycol (Ethylene Glycol), glycerol (Glycerol), dimethyl
  • the solution may be a solution in which NH 4 F is mixed with at least one solution selected from dimethyl sulfoxide (DMSO).
  • Titanium or a titanium alloy is prepared to form a TiO 2 nanotube array, and mounted on the anode 30.
  • As the cathode 40 acid resistant metal electrodes such as platinum (Pt), tantalum (Ta), silver (Ag), and gold (Au) are used.
  • the positive electrode 30 is installed to be immersed in the electrolyte 20 by maintaining a constant interval with the negative electrode 40.
  • the positive electrode 30 and the negative electrode 40 are connected to a power supply 50 for applying a voltage or current.
  • the voltage difference between the anode 30 and the cathode 40 is appropriately adjusted in consideration of the diameter size of the TiO 2 nanotubes formed, the length of the TiO 2 nanotubes, and the like.
  • the voltage applied to form the TiO 2 nanotube array formed by the first anodization is preferably applied so that the voltage difference between the anode and the cathode is less than or equal to 80V.
  • the TiO 2 nanotube array formed by the first anodization has a tubular structure in which the upper portion is open and the lower portion is closed, and the inner diameter of the TiO 2 nanotube array is preferably 10 to 300 nm.
  • the electrolytic cell 10 is equipped with a chiller 85 to prevent a sudden temperature rise due to an exothermic reaction during the anodization process and to increase the uniformity of the electrolysis or chemical reaction throughout the metal film.
  • a magnetic stirrer (80) and a stirring magnetic bar (Stirring Magnetic Bar) 90 may be provided to facilitate anodization by stirring.
  • a temperature control device such as a hot plate for maintaining a constant temperature in the electrolytic cell may be provided.
  • the temperature of the electrolytic cell 10 is set to about 0-50 degreeC.
  • the electrolyte 20 facilitates the movement of charged electrons or ions to form a titanium oxide film (TiO 2 ) on the surface of titanium (Ti) or titanium alloy. Titanium metal ions (Ti 4+ ) are dissolved in the electrolyte solution 20 at the interface between the electrolyte solution 20 and the oxide film, and the electrolyte solution 20 combines with O 2 ⁇ and OH ⁇ ions to form an oxide film at the oxide film and the metal interface. do.
  • the electrolytic solution 20 in the water molecule (H 2 O), by the electrolysis of hydrogen ions as in reaction scheme 1 below (H +) and hydroxyl ion (OH -) are delivered in.
  • Hydrogen ions (H + ) move toward the cathode 40 and are released as hydrogen gas (H 2 ) by bonding electrons between the electrolyte solution 20 and the surface of the cathode 40.
  • the hydroxyl group ion (OH ⁇ ) moves toward the anode 30 and is separated into oxygen ions (O 2 ⁇ ) and hydrogen ions (H + ) in a natural oxide film formed on the surface of the anode 30.
  • the separated oxygen ions (O 2- ) penetrate the natural oxide film and react with titanium ions (Ti 4+ ) between the natural oxide film and titanium (or titanium alloy) to form a titanium oxide film (TiO 2 ) as shown in the following Reaction Formula 2 below. Done.
  • H + hydrogen ions react with the titanium oxide film (TiO 2 ) to partially break the bond between titanium (Ti) and oxygen to form a hydroxide, which is dissolved in the electrolyte solution 20. That is, oxide etching occurs on the surface between the titanium oxide film TiO 2 and the electrolyte solution 20.
  • the titanium oxide film TiO 2 is formed at the interface between the natural oxide film and the titanium (or titanium alloy).
  • TiO 2 titanium oxide film
  • the titanium oxide film (TiO 2 ) thus formed is dissociated by a small amount of fluorine ions (F ⁇ ) contained in the electrolyte solution as in Scheme 4.
  • This dissociation action occurs over the entire titanium oxide layer (TiO 2 ) and forms a nanotube array.
  • the oxidation reaction of Scheme 3 and the dissociation reaction of Scheme 4 occur simultaneously, thereby obtaining a nanotube array.
  • the TiO 2 nanotube array formed on the surface of the titanium metal or titanium alloy is removed by sonication.
  • the ultrasonic wave refers to a sound wave having a frequency of 20kHz or more, and the frequency of the ultrasonic wave for removing the TiO 2 nanotube array may be about 28 to 40kHz.
  • the TiO 2 nanotube array formed on the surface of the titanium metal or titanium alloy is removed while falling off from the surface of the titanium metal or titanium alloy.
  • the first TiO 2 nano-tube array generated by the anodization is not a drug with ease because a lot of parts that clogged the pores of the nanotubes to dirty the surfaces, and thus claim the TiO 2 nanotube array formed by the first anodizing removal and, TiO 2 nano-tubes will the array to form a TiO 2 nanotube array having a clean surface through the second anode oxide with respect to titanium metal or titanium alloy of the removed surface, TiO 2 nano-formed by the second anodizing Most of the pores of the tube array are open, making it easy to mount the drug.
  • the second oxide cathode using the electrolytic solution containing fluorine (F) with respect to the titanium metal or titanium alloy of the removed surface of the TiO 2 nanotube array to form a TiO 2 nanotube array.
  • the anode and the cathode on which the titanium metal or the titanium alloy is disposed are spaced apart from each other, and the anode and the cathode are immersed in the electrolyte in the electrolyte containing the electrolyte, and a voltage is applied to the anode and the cathode.
  • the voltage applied to form the TiO 2 nanotube array formed by the second anodization is preferably applied so that the voltage difference between the anode and the cathode is less than or equal to 80V.
  • the electrolyte for the second anodization is sulfuric acid (H 2 SO 4 ), phosphoric acid (H 3 PO 4 ), citric acid (citric acid), oxalic acid (oxalic acid), ethylene glycol (Ethylene Glycol), glycerol (Glycerol), dimethyl
  • the solution may be a solution in which NH 4 F is mixed with at least one solution selected from dimethyl sulfoxide (DMSO).
  • the TiO 2 nanotube array formed by the second anodization has a tubular structure in which the upper portion is open and the lower portion is closed, and the inner diameter is preferably 10 to 300 nm.
  • the drug is loaded into the TiO 2 nanotube array formed by the second anodization.
  • the drug may include at least one substance selected from recombinant human bone morphogenetic protein-2 (rhBMP-2) and an anti-inflammatory agent.
  • the columnar porous titania TiO 2 nanotube array can be formed by performing two-step anodization (first anodization and second anodization) on a pure titanium or titanium alloy surface, and aligned There is a huge advantage due to the nanostructure. Since the surface area is significantly increased and the surface shape can be changed to resemble the original bone tissue, the formation of the implant surface can enhance bone adhesion.
  • TiO 2 nanotube arrays with controlled diameters of voids can be produced.
  • TiO 2 nanotube surfaces with optimal lengths for cell adhesion and differentiation can induce the migration of osteoblasts and mesenchymal stem cells, thus Enhances the interaction between the implant surface and the cells.
  • the empty space of the TiO 2 nanotubes can act as a drug reservoir.
  • Drugs such as antibiotics, anti-inflammatory drugs and growth factors are prescribed to be injected into the mouth, veins and muscles. However, some drugs are not effective when delivered through this route. Systemic delivery of these drugs can lead to adverse effects and organ toxicity at high concentrations. Thus, local drug therapy is becoming an accepted type of treatment.
  • rhBMP-2 Recombinant human bone morphogenetic protein-2
  • rhBMP-2 Appropriate amounts of rhBMP-2 induce bone formation, but too much may be associated with unwanted effects.
  • Systemic delivery of rhBMP-2 can have unwanted effects because it has uncontrolled adverse effects such as unwanted ectopic bone formation. Therefore, rhBMP-2 must be anchored to the implant surface to allow sufficient time to promote osteoadhesion.
  • TiO 2 nanotube arrays were formed on the surface of the dental implant by two-step anodization.
  • TiO 2 nanotube arrays provide an empty space for drug loading and show biocompatibility.
  • a dental implant with a TiO 2 nanotube array a structure suitable for inserting drugs such as antibiotics, anti-inflammatory agents and growth factors, was designed.
  • rhBMP-2 is loaded into the storage space of TiO 2 nanotube arrays. The effects of TiO 2 nanotube arrays and rhBMP-2 on implant-bone adhesion and remodeling in dental implants were investigated by in vivo experiments and in vitro tests in rabbits.
  • TiO 2 nanotube arrays were prepared on the surface of the implant by two-step anodization using an electrolyte comprising ethylene glycol and 0.5% by weight of NH 4 F. To obtain an appropriate microstructured TiO 2 nanotube array, the anodization voltage and time were computer controlled by a LabVIEW program by a DC power supply.
  • Two -step anodization was performed to obtain clean surfaces and open windows of the TiO 2 nanotube array.
  • the implant was first oxidized at a voltage of 60V and 60 minutes.
  • TiO 2 nanotube arrays prepared by first anodization were removed by sonication.
  • a TiO 2 nanotube array with clean open windows was finally produced by second anodization.
  • the voltage and time of the second anodization were 15V and 15 minutes.
  • the thickness and open window size of the TiO 2 nanotube arrays were observed by field emission scanning electron microscopy (FESEM).
  • rhBMP-2 (Cowellme Co., Busan, Korea) was loaded into the interior space of the TiO 2 nanotube array by a dip coating process in a vacuum chamber.
  • the concentration of rhBMP-2 was 1.5 mg / ml.
  • Each implant was immersed three times in rhBMP-2 solution for 5 seconds and dried at a temperature of 20 ° C.
  • Figure 2 is a schematic diagram showing the configuration of the device to observe by interferometric biosensing method for TiO 2 nanotube array.
  • the incident white light source 100 uses a tungsten lamp.
  • the surface where white light is incident on the TiO 2 nanotube array using an optical fiber and a lens is preferably focused to be included in a circle having a diameter of 0.1 to 1 mm.
  • the reflected light interfering from the TiO 2 nanotube array 15 may be collected using the CCD spectrometer 110.
  • reference numeral 5 denotes titanium (Ti).
  • the CCD spectrometer 110 may measure the change in intensity according to the wavelength of the reflected light spectrum, and the drug is administered to the TiO 2 nanotube array. It is possible to measure the change in intensity depending on the wavelength of the reflected light spectrum in the state.
  • the Fabry-Faro interference phenomenon will be described.
  • the mirrors with high reflectivity are placed in parallel with each other and the light is incident on the mirror, the light transmitted through the mirror transmits a part of light from the surface of the parallel mirror, but most of the time, the transmission and reflection are repeated.
  • the number of reflections between the two mirrors passes through the lower mirror, and each light exhibits interference as much as the path difference.
  • the optical thickness described above the distance between the lower end portion of the pores on the other side in the longitudinal direction of the TiO 2 nanotube array on the upper end of the pore, that is the length of the space in which the drug loaded in the TiO 2 nanotube array. At this time, if the drug is contained between the upper end of the pores and the lower end of the pores, the thickness of the drug is the optical thickness.
  • Equation 1 shows the relationship between the refractive index (n) and the optical thickness (L).
  • n the refractive index of the drug contained in the TiO 2 nanotube array and TiO 2 nano-tube array
  • L is the TiO 2 nanotube array optical thickness of (optical thickness).
  • the optical thickness L can be changed according to the concentration of the electrolyte, the voltage, the anodization time, and the like. As the length of the optical thickness increases, the number of fringes increases and the characteristics of the interference wavelength change.
  • TiO 2 nanotubes irradiated with a white light on the array TiO 2 nano-tube array fabrication by the optical path difference between the top and the bottom of the pore-form of the reflected wave when the fringe losses.
  • the Fabry-Faro Fringe-shaped reflection waveform can confirm the change in the intensity of the white light and the shift of the reflection wavelength.
  • a fast fourier transformation (FFT) of the spectra for the reflection wavelength in the form of Fabry-Faroe fringes against white light is attempted.
  • the fast Fourier transform is an algorithm designed to reduce the number of operations when computing a discrete fourier transform using an approximation formula based on the Fourier transform.
  • Fast Fourier transform is a function calculation method that converts sound information of a temporal flow into a flow of frequency.
  • the reflected light spectrum obtained from the TiO 2 nanotube array is subjected to fast Fourier transform (FFT).
  • FFT fast Fourier transform
  • a peak having a specific optical thickness can be obtained, and this optical thickness is called an effective optical thickness.
  • This effective optical thickness shifts as the spectrum changes depending on the size and refractive index of the drug in the TiO 2 nanotube array.
  • This effective optical thickness is based on the sensing of loading and elution of specific drugs by attaching appropriate capture probes to TiO 2 nanotube inner surfaces and using specific binding. It is possible.
  • the machined implant shown in FIGS. 3A and 3B is a view showing a typical image and microstructure of a titanium implant.
  • the processing implant has unidirectional processed grooves. By using a CNC mechanism, the surface is smooth as shown in Fig. 3B.
  • 4A and 4B show rough surface images and microstructures of sandblasted large-grit and acid-etched (SLA) implants.
  • TiO 2 nanotube arrays prepared by two-step anodization. It can be seen that the surface of the TiO 2 nanotube array is less rough than the surface of the SLA implant. However, TiO 2 nanotube arrays have nano-sized holes for loading drugs such as BMP-2, PEP7, ibuprofen.
  • FIG. 6A to Figure 6d is a diagram showing the TiO 2 nanotube array FESEM image of the surface and TiO 2 nano-tube array is loaded in the rhBMP-2.
  • FIG. 6A is an FESEM image of the TiO 2 nanotube array
  • FIG. 6B is an enlarged image of FIG. 6A
  • FIG. 6C is an FESEM image of the TiO 2 nanotube array loaded with rhBMP-2
  • FIG. 6D is an enlarged image of FIG. 6C. to be.
  • TiO 2 nanotube arrays were prepared by two-step anodic oxidation. TiO 2 The diameter of the nanotubes windows and TiO 2 nano-tubes, each was ⁇ 70nm and ⁇ 110nm.
  • the windows of TiO 2 nanotubes are clean and open, and these microstructures are suitable for loading drugs.
  • the thickness of the TiO 2 nanotubes was about 17 ⁇ m, as shown in FIG. 6A.
  • the window of the TiO 2 nanotubes is slightly blocked by rhBMP-2 loading.
  • the diameter of the TiO 2 nanotube window was reduced to ⁇ 50 nm by rhBMP-2 loading. RhBMP-2 loaded on the surface is expected to improve osteoadhesion.
  • rhBMP-2 In order to observe the elution of rhBMP-2 from the TiO 2 nanotube array, an interferometric biosensing method with a flow cell was used.
  • deionized water DI water
  • DI water deionized water
  • the optical thickness change of rhBMP-2 was monitored in real time.
  • 7 is a graph showing the change in optical thickness for 10 days according to rhBMP-2 loading. Baseline was established with an optical thickness of DI water for 20 hours.
  • the solution containing rhBMP-2 was derived by deionized water passing through a dental implant with a TiO 2 nanotube array loaded with rhBMP-2.
  • Optical thickness was increased by elution of rhBMP-2 from TiO 2 nanotube arrays, and slowly increased for 9 days.
  • RhBMP-2 was selected as a drug to improve new bone formation and osteoinduction around the implant surface and evaluated the possibility of using TiO 2 nanotube arrays as drug reservoirs.
  • Dental implants were divided into four groups. The surface of the implant, the implant SLA, TiO 2 nanotube array surface of the implant, and TiO 2 nano-tube array surface implant containing rhBMP-2 were processed respectively named groups I1, I2 group, group I3, I4 group. Four groups of implants were placed in the proximal tibia of the rabbit for 8 weeks. After eight weeks, all the implants were in direct contact with histologically surrounding bones along the stem.
  • I1 group I2 group I3 group I4 group Bone to implant contact (%) 11.1 ⁇ 17.0 14.7 ⁇ 9.5 16.3 ⁇ 11.9 29.5 ⁇ 3.8 Bone volume ratio (%) 66.9 ⁇ 6.7 53.7 ⁇ 11.5 67.2 ⁇ 7.6 77.3 ⁇ 8.8
  • the maximum BIC (bone to implant contact ratio) of the I4 group was 29.5%, and the I3, I2, and I1 groups were 16.3%, 14.7%, and 11.1%, respectively. Bone volume ratios were measured around the implant threads. The highest bone volume fraction of 77.3% was found in the I4 group. The bone volume fractions of the I3, I2, and I1 groups were 67.2%, 53.7%, and 66.9%, respectively.
  • TiO 2 nanotube array surface implants have a greater bone adhesion effect than the surface implants processed with the TiO 2 nanotube array surface implants or the SLA implants, and the biochemical effects of bone induction in TiO 2 nanotube array surface implants containing rhBMP-2. To show that it has.
  • TiO 2 nanotube arrays are believed to enhance bone formation and cell adhesion effects.
  • TiO 2 nanotube arrays have excellent oxide microstructures for new bone growth and can affect bone composition for protein interaction, fast and permanent bone adhesion.
  • TiO 2 nanotube arrays enhance wettability and can function as drug reservoirs. TiO 2 nanotube implants with rhBMP-2 may increase bone formation.
  • the I4 group loaded with rhBMP-2 on the TiO 2 nanotube array showed high BIC (bone to implant contact ratio) and bone volume ratio for 8 weeks. This demonstrates the long lasting effect of rhBMP-2, where bone remodeling, bone formation and bone reduction occur slowly.
  • FIGS. 9-12 show four groups of fluorescence and histologic staining images observed with an optical microscope.
  • the fluorescence and histological staining images shown in FIGS. 9-12 show the right and left sides, respectively.
  • Fluorescent images are formed by fluorochrome labeling with alizarin red and calcein green.
  • Other patterns of bone formation and bone remodeling were observed in four groups. Red and green represent new bone formations formed for 3 and 6 weeks after implant placement, respectively.
  • Bone formation and bone remodeling, indicated by white arrows, were mainly observed near the periosteum in the I1, I2 and I3 groups. However, bone formation and bone remodeling in the I4 group were observed near all implant threads as well as near the periosteum.
  • Bone formation and bone remodeling in the I1, I2 and I3 groups can be explained by osteoblast-rich periosteum.
  • I4 group abundant bone formation and bone remodeling in the implant stem is due to the osteoogenesis effect of rhBMP-2 eluted from TiO 2 nanotube arrays.
  • the I4 group showed stronger fluorochrome labeling. Fluorescent pigment labeling around the periosteum reflects bone formation, and fluorescent pigment labeling around the implant stem is believed to be bone remodeling and improve bone adhesion.
  • TiO 2 nanotube arrays comprising rhBMP-2 can enhance bone formation and bone remodeling in the vicinity of the implant, thus enhancing bone adhesion to the surface of the dental implant.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dentistry (AREA)
  • Birds (AREA)
  • Materials For Medical Uses (AREA)
  • Engineering & Computer Science (AREA)
  • Manufacturing & Machinery (AREA)

Abstract

La présente invention concerne un procédé de fabrication d'un implant dentaire chargé de médicament, comprenant les étapes consistant à : former un réseau de nanotubes de TiO2 par anodisation principalement de métal de titane ou d'alliage de titane à l'aide d'un électrolyte contenant du fluor (F); enlever le réseau de nanotubes de TiO2 formé sur la surface du métal de titane ou de l'alliage de titane par l'utilisation d'ultrasons; former un réseau de nanotubes de TiO2 secondairement par anodisation de métal de titane ou d'alliage de titane de la surface, à partir de quoi le réseau de nanotubes de TiO2 a été enlevé, en utilisant l'électrolyte contenant du fluor (F); et le chargement d'un médicament dans le réseau de nanotubes de TiO2 formé à partir de l'anodisation secondaire. Selon la présente invention, un implant dentaire ayant un rapport de contact élevé de l'os à l'implant (BIC) et un taux élevé de volume osseux peut être fabriqué.
PCT/KR2015/005275 2015-04-24 2015-05-27 Procédé de fabrication d'implant dentaire chargé de médicament Ceased WO2016171310A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2015-0057639 2015-04-24
KR1020150057639A KR20160126513A (ko) 2015-04-24 2015-04-24 약물이 로딩된 치과용 임플란트의 제조방법

Publications (1)

Publication Number Publication Date
WO2016171310A1 true WO2016171310A1 (fr) 2016-10-27

Family

ID=57144617

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2015/005275 Ceased WO2016171310A1 (fr) 2015-04-24 2015-05-27 Procédé de fabrication d'implant dentaire chargé de médicament

Country Status (2)

Country Link
KR (1) KR20160126513A (fr)
WO (1) WO2016171310A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108439546A (zh) * 2018-03-01 2018-08-24 南京大学 自掺杂TiO2纳米管电极、制备方法及其应用
CN115074745A (zh) * 2022-04-16 2022-09-20 重庆大学 一种五氧化二钽纳米管阵列薄膜的制备方法
US12150850B2 (en) 2018-03-01 2024-11-26 Titanium Textiles Ag Tension-free titanium metal knitted fabric for surgically shaping soft tissues
US12186193B2 (en) 2018-03-01 2025-01-07 Titanium Textiles Ag Titanium matrix based on a tension-free metal warp knit fabric for guided tissue regeneration

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106983523B (zh) * 2017-03-15 2020-04-10 北京科技大学 一种牙科种植体及其弱碱性纳米表面的制备方法
KR20180106457A (ko) * 2017-03-20 2018-10-01 강릉원주대학교산학협력단 치아 교정용 나사
KR102109949B1 (ko) 2018-12-14 2020-05-11 전남대학교산학협력단 염화물과 펄스 전원을 이용한 티타늄 임플란트 재료의 표면 처리 방법 및 그로부터 표면 처리된 티타늄 임플란트
KR102339807B1 (ko) 2019-06-26 2021-12-14 최참 골-임플란트 접촉 비율 측정 장치 및 방법
CN113046812A (zh) * 2021-02-09 2021-06-29 佛山市安齿生物科技有限公司 一种用于钛合金牙科基台系统的阳极氧化液及其制备方法和应用
CN115970057B (zh) * 2022-09-09 2024-05-28 浙江科惠医疗器械股份有限公司 一种具有花瓣状TiO2纳米孔抗菌涂层的制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20110051441A (ko) * 2009-11-10 2011-05-18 전북대학교산학협력단 치과용 임플란트 표면에 나노튜브를 신속하고도 균일하게 형성시키는 방법
KR20120120784A (ko) * 2011-04-25 2012-11-02 강릉원주대학교산학협력단 산화티타늄 나노튜브를 이용한 생체삽입물
KR101345118B1 (ko) * 2011-06-24 2013-12-26 한국기계연구원 수용액 전해질 내에서 양극산화에 의한 산화 티타늄 나노튜브 제조방법
KR20140030475A (ko) * 2012-08-30 2014-03-12 한양대학교 에리카산학협력단 광전극과 염료감응형 태양전지의 제조방법, 이에 따라 제조된 염료감응형 태양전지의 광전극

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100856031B1 (ko) 2007-03-19 2008-09-02 강릉대학교산학협력단 다공성 임플란트 및 그 제조방법

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20110051441A (ko) * 2009-11-10 2011-05-18 전북대학교산학협력단 치과용 임플란트 표면에 나노튜브를 신속하고도 균일하게 형성시키는 방법
KR20120120784A (ko) * 2011-04-25 2012-11-02 강릉원주대학교산학협력단 산화티타늄 나노튜브를 이용한 생체삽입물
KR101345118B1 (ko) * 2011-06-24 2013-12-26 한국기계연구원 수용액 전해질 내에서 양극산화에 의한 산화 티타늄 나노튜브 제조방법
KR20140030475A (ko) * 2012-08-30 2014-03-12 한양대학교 에리카산학협력단 광전극과 염료감응형 태양전지의 제조방법, 이에 따라 제조된 염료감응형 태양전지의 광전극

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LEE, J .-K. ET AL.: "Improved Osseointegration of Dental Titanium Implants by Ti02 Nanotube arrays with Recombinant Human Bone Morphogenetic Protein-2: A Pilot In Vivo Study", INTERNATIONAL JOURNAL OF NANOMEDICINE, vol. 10, 5 February 2015 (2015-02-05), pages 1145 - 1154, XP055323446 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108439546A (zh) * 2018-03-01 2018-08-24 南京大学 自掺杂TiO2纳米管电极、制备方法及其应用
US12150850B2 (en) 2018-03-01 2024-11-26 Titanium Textiles Ag Tension-free titanium metal knitted fabric for surgically shaping soft tissues
US12186193B2 (en) 2018-03-01 2025-01-07 Titanium Textiles Ag Titanium matrix based on a tension-free metal warp knit fabric for guided tissue regeneration
CN115074745A (zh) * 2022-04-16 2022-09-20 重庆大学 一种五氧化二钽纳米管阵列薄膜的制备方法
CN115074745B (zh) * 2022-04-16 2024-02-09 重庆大学 一种五氧化二钽纳米管阵列薄膜的制备方法

Also Published As

Publication number Publication date
KR20160126513A (ko) 2016-11-02

Similar Documents

Publication Publication Date Title
WO2016171310A1 (fr) Procédé de fabrication d'implant dentaire chargé de médicament
Kodama et al. Bioactivation of titanium surfaces using coatings of TiO2 nanotubes rapidly pre-loaded with synthetic hydroxyapatite
KR100856031B1 (ko) 다공성 임플란트 및 그 제조방법
Cipriano et al. Anodic growth and biomedical applications of TiO2 nanotubes
Das et al. TiO2 nanotubes on Ti: Influence of nanoscale morphology on bone cell–materials interaction
US20070187840A1 (en) Nanoscale probes for electrophysiological applications
Ion et al. Nanochannels formed on TiZr alloy improve biological response
Acciari et al. Surface modifications by both anodic oxidation and ion beam implantation on electropolished titanium substrates
KR101281722B1 (ko) 다공성 티타늄 산화막을 이용하여 생체활성 물질의 담지율을 높이는 임플란트 재료의 제조방법 및 이에 의한 임플란트 재료
Patel et al. Transparent TiO 2 nanotubes on zirconia for biomedical applications
Fohlerova et al. Anodic formation and biomedical properties of hafnium-oxide nanofilms
Louarn et al. Nanostructured surface coatings for titanium alloy implants
Moravec et al. Cell interaction with modified nanotubes formed on titanium alloy Ti-6Al-4V
Das et al. Biocompatibility and in situ growth of TiO2 nanotubes on Ti using different electrolyte chemistry
Yoon et al. Aligned nanowire growth using lithography-assisted bonding of a polycarbonate templatefor neural probe electrodes
JP2010215438A (ja) 酸化チタン膜および酸化チタン膜形成方法
Moon et al. Bioactivity of Ti‐6Al‐4V alloy implants treated with ibandronate after the formation of the nanotube TiO2 layer
Guo et al. Optimizing titanium implant nano-engineering via anodization
ITMI20110312A1 (it) Impianto dentale con superficie nanostrutturata e procedimento per il suo ottenimento
Chopra et al. Random, aligned and grassy: Bioactivity and biofilm analysis of Zirconia nanostructures as dental implant modification
WO2020050579A1 (fr) Procédé de formation d'un film d'apatite au moyen d'un laser
Schweicher et al. Facile synthesis of robust free-standing TiO2 nanotubular membranes for biofiltration applications
Zhang et al. Neuron-like cell differentiation of hADSCs promoted by a copper sulfide nanostructure mediated plasmonic effect driven by near-infrared light
Miyabe et al. TiO2 nanotubes with customized diameters for local drug delivery systems
Minagar et al. Cell response and bioactivity of titania–zirconia–zirconium titanate nanotubes with different nanoscale topographies fabricated in a non-aqueous electrolyte

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15889976

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15889976

Country of ref document: EP

Kind code of ref document: A1