WO2020104840A1 - Dental implant activation box used for surface activation with uv c - Google Patents
Dental implant activation box used for surface activation with uv cInfo
- Publication number
- WO2020104840A1 WO2020104840A1 PCT/IB2018/059246 IB2018059246W WO2020104840A1 WO 2020104840 A1 WO2020104840 A1 WO 2020104840A1 IB 2018059246 W IB2018059246 W IB 2018059246W WO 2020104840 A1 WO2020104840 A1 WO 2020104840A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- implant
- implants
- dental
- titanium
- stand
- Prior art date
Links
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- 230000004913 activation Effects 0.000 title claims abstract description 37
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
- A61C8/0087—Means for sterile storage or manipulation of dental implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/088—Radiation using a photocatalyst or photosensitiser
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/10—Ultraviolet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/20—Gaseous substances, e.g. vapours
- A61L2/202—Ozone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
- A61L2202/10—Apparatus features
- A61L2202/18—Aseptic storing means
- A61L2202/182—Rigid packaging means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
- A61L2202/20—Targets to be treated
- A61L2202/21—Pharmaceuticals, e.g. medicaments, artificial body parts
Definitions
- the invention is about a package that improves the titanium dental implant's physiochemical and biological characteristics by the help of a (UV) light source and a renovation on its working method.
- Dental implants have been used for the rehabilitation of total or partial tooth loss, since their invention by Per Ingvar Branemark. Although they can be fabricated from different materials (e.g. peek, ceramics, zirconia), the highly preferred material for production is titanium and its alloys. The first implants that were fabricated had machined surfaces. In time, in order to improve osseointegration properties, many studies have been carried out on for altering surface chemistry and topography. Regarding this, two different processes were applied: a) Additive Techniques: TPS (Titanium Plasma Spray), Hydroxyapatite coating b) Subtractive Technique: Sandblasting with different media (AI 2 O 3 , T1O 2 , CaO) and Acid etching (with different acids, processing times and temperatures)
- Titanium which is used as a dental implant material, is corrosion resistant due to naturally formed T1O 2 layer on its surface, biocompatible and has osseointegration dependent load bearing capacity as well. It can make structural and functional bonding between the implant surface and surrounding bone tissue, without forming fibrous tissues.
- Osseointegration (01), can be described as the direct structural and functional bonding between a host hard tissue and the surface of a load-covering implant at the histological level.
- Osseointegration (01) can be described as the direct structural and functional bonding between a host hard tissue and the surface of a load-covering implant at the histological level.
- it results in the fixation of implants into the host tissue in long-term stability and rigidity
- Osseointegration is highly required for primary stability of implants and therefore is a very important factor which should be considered prior to following treatments.
- bone formation proceeds by attachment, settlement, the proliferation of osteoblasts which is followed by their maturation.
- mineralization occurs around the released proteins.
- Many biological phenomena occur around the bone- implant interface which is identical to bone healing.
- the healing process initiates within a few seconds as soon as the blood contacts the surface of the implant.
- the coagulation cascade is started by thrombocytes, afterwards, phagocytic cells migrate to the inflammatory site as well.
- Bio Biological aging can be defined as the physiochemical degradation of the implant surface in relation to time. It is reported that after an appropriate healing period of titanium replacement, osseointegration level is not sufficient as the bone-implant contact stays below 100%.
- This situation is related to the carbon deposition, which is unavoidable and is formed by airborne hydrocarbons resulting in hydrocarbon adsorption on the titanium implant surface. This leads to a certain lack of hydrophilicity and loss in surface charge. Eventually, physiochemical and biological properties are spoiled, e.g. decrease in osteoconductivity, poor osteogenic proliferation, and low absorption of serum proteins.
- UV light Ultraviolet light wavelengths can be classified as UV A (320-400nm) UV B (290-320nm) and UV C (10-290nm).
- UV A 320-400nm
- UV B 290-320nm
- UV C 10-290nm
- hydrocarbons are removed by UV A through inducing T1O2 photocatalysis
- UV C irradiation is more effective in the surface hydrocarbon reduction, which than improves hydrophilicity, enhances the adsorption of proteins and cell function, respectively.
- the affinity of proteins to the implant surface is improved by photofunctionalization via causing various physiochemical changes on the titanium surface.
- the process is described as follows: a) Removing unavoidable hydrocarbons adsorbed on the surface b) Increasing the degree of hydrophilicity c) Shifting the surface charge from electronegative to electropositive, which can improve cell adhesion behavior.
- the wettability of the surfaces by aqueous solutions can be defined as hydrophilicity.
- hydrophilicity When water drops on a hydrophobic surface, the droplet shape is retained, whereas it floats out when the surface is hydrophilic.
- the angle between the solid surface and the tangent line of the liquid phase at the interface of the solid-liquid phases is called the contact angle.
- the contact angle When the contact angle is less than 5 degrees, the surface is "hydrophilic".
- the contact angle approaches to 0 degrees water completely wets the surface, and this is called super hydrophilicity.
- titanium surface aging could be attributed to low protein and osteogenic cell adhesion resulted by adsorption of airborne hydrocarbons on the surfaces under ambient conditions.
- the zeta potential of the titanium surface shifts from electropositive to electronegative; which prevents negatively charged blood protein and extracellular matrix adhering to the surface.
- Titanium surface aging gradually induces the hydrophobicity abruptly to a contact angle over 40 degrees in 2 weeks, 60 degrees in 4 weeks, respectively.
- Airborne hydrocarbons are the molecules, which are responsible for the hydrophobicity of TiC surfaces. Hydrocarbons form weak bonds with T1O2 and they adsorb on the surface of the implant.
- Bolon and Kunz reported that a variety of photoresist polymers can be depolymerized using UV light exposure. They kept the polymer films in a quartz tube filled with oxygen. UV light which was obtained from a medium-pressure mercury lamp generates ozone. In less than one hour of UV treatment, successful depolymerization of polymer thin films were observed, with the release of water and carbon dioxide. By placing a pyrex filter between the UV light and the polymer or, by using nitrogen atmosphere instead, the depolymerization was interrupted.
- Vig et al. conducted experiments on the determination of optimal conditions for clean surface production via UV irradiation.
- the parameters of UV cleaning were well-defined, and it was indicated that, under appropriate conditions, clean surfaces can be obtained in less than one minute by UV/ozone cleaning.
- T1O 2 Under UV irradiation, T1O 2 exhibits photocatalytic reactivity in order to decompose various organic compounds into CO 2 and H 2 O.
- two sorts of UV sources can be used.
- the decomposition of carboxylic acids and/or aldehydes were slow by T1O 2 photocatalysts; since there was strong interaction between carboxylic compounds and the Ti 4+ sites of the TiC surfaces.
- UV Ozone cleaning The principles of UV Ozone cleaning can be described as follows:
- Organic compounds are decomposed into volatile products (e.g water, carbon dioxide, nitrogen) by UV and strong oxidation during the formation and decomposition of 03.
- the major wavelengths of the UV irradiation which is obtained from a low-pressure mercury lamp are sorted as 184.9 nm and 253.7 nm.
- the corresponding wavelengths are emitted in correlation to the lamp envelopes. It should be noted that both wavelengths can be transmitted through pure quartz.
- the 184.9 nm wavelength is crucial. This finally leads to generation of ozone.
- This wavelength can also be absorbed by various organic molecules. Oxygen cannot absorb 253.7 nm radiations.
- the corresponding wavelength does not play any role in ozone generation, although it can be absorbed both by most of the organic molecules and ozone.
- the decomposition of ozone in the UV box or chamber occurs due to ozone absorption. Therefore, in this presence of both wavelengths (as it is in the UV box or chamber), ozone can be formed and decomposed continuously.
- Atomic oxygen is formed as an intermediate product during formation and decomposition processes; which is an unstable and a very effective oxidizing agent.
- Photoactivation is the technique for enhancing the bioactivity of titanium implant surfaces by the use of UV light source without altering its roughness or other morphological structures, but its physicochemical properties. This can be included in neither additive nor subtractive techniques of preparing implant surfaces. Treating with UV is simple, low-cost and can be applied on any kind of implant surfaces for their activation. Titanium which is used in dental implants and orthopedic implants, are coated with a native oxide (T1O2) layer due to its interaction with air. Since these implants are served to the end-users inside gas permeable packages as an ultimate product it is always affected by airborne hydrocarbons from the atmosphere, while it also adsorbs hydrocarbons from water and cleaning solutions during production process. Therefore, adsorption of hydrocarbons on titanium surfaces is unavoidable.
- T1O2 native oxide
- IN-VITRO Protein adsorption speed and capacity is one of the critical important criteria of biocompatibility for implantable materials. a) Fibronectin adsorption, which is responsible for osteoblast adhesion and proliferation, is observed as 40% less for 4-week aged surfaces when compared to newly processed after 6 hours of incubation. This decrease is observed similarly for 24 hours of incubation.
- albumin Another protein, which is affected by the aging of titanium, is albumin.
- Albumin forms 60% of plasma proteins and acts as a carrier of molecules which are poor soluble in water including hormones and calcium.
- Albumin bound lipids regulate the secretion of calcium and differentiation of osteoblasts on cellular level (cytoplasmic).
- Adsorption of albumin decreases to 50% on the 4-week aged surfaces compared to newly processed after 6 hours of incubation. Adsorption dramatically decreases after 24 hours of incubation. For instance, the level of albumin adsorption is observed as 20% of newly processed surfaces compared 3-months aged titanium surfaces.
- Alkalene Phosphatase (ALP) Activity is also negatively affected from the ageing of titanium. ALP which is responsible from the differentiation and mineralization of osteoblasts is found in all cells of human body and especially at high level in bone tissues. Elevated ALP level is an indicator of bone apposition. When compared to newly processed surfaces, ALP activity is 60% decreased on aged surfaces. Calcium deposition is observed as 50% less for 4-week aged surfaces when compared to newly processed.
- periimplant osteogenesis was morphologically and morphometrically investigated, as new bone formation at high amount is observed around newly processed implant, while, local and partial bone formation is observed to form around 4-week aged implant, within 2 weeks of early healing period.
- the soft tissue intervention is observed to be high at the interface between newly formed bone and the implant surface in the 4-week aged implants. The soft tissue intervention is rarely observed in the newly processed implants.
- Bone Implant Contact is measured 2.3 times more in the 2-weeks early healing period and 1.6 times more in 4-weeks healing period in newly processed implants compared to 4-week aged implants.
- UV treated surface has two times more migrated cells compared to newly processed surface whereas it is four times more compared to 4 week aged surface for three hours incubation.
- the number of cells attached to the 4 weeks old surface was %50 less than the newly processed surface.
- the UV treated 4 weeks old surface showed %120 higher cell attachment than newly processed surface in 24 hours of incubation
- the titanium discs prepared for control and test groups were seeded with bacteria and dried for 30 minutes. Later on, they treated the test group with UV C, then they harvested bacteria both from test and untreated discs. During measurement, they observed that there is no bacterial colonization on the UV treated disc. Hence this showed the bactericidal effect of the UV treated surface.
- the implants After 15 or 20 minutes of activation, the implants has to be taken out from the platform and transferred to the patient's mouth, again by avoiding any contact to the non-sterile devices and places.
- the dentist prepares the proper length and width of implant bed and places the related implant into the implant bed with an implant driver. This is the dentist's routine without the use of device. However in case the dentist wants to use this device for surface activation, there will be extra steps demanding special care.
- the dental implant In current condition, the dental implant is being taken off from its gamma sterilized original package and from its implant stand, then with an implant driver, it is being carried to the light source in order to make the surface activation. Therefore, this procedure obliges the dentist going out of routine.
- the dentist will keep its routine during surgery. According to our invention, the dentist will not need to carry the dental implant to another device for light source to surface activation anymore.
- the dental implant is placed into the dental implant activation box with CCFL (Cold Cathode Fluorescent Lamp) UV C together; then, is sealed and isolated from the outer environment. After gamma sterilization, the dental implant activation box will be delivered to the end user (dentists). Since the implant has a light source inside their box, and since it will be activated with its sealed and isolated condition, the gamma sterilization chain will not be broken, therefore in case of there is uncertainty about diameter and length, the alternative dental implants activated will keep its possibility to be used for another patient.
- CCFL Cold Cathode Fluorescent Lamp
- Another problem faced in current condition is that, even if all the implants diameters are the same, the dentist will need the same amount of the implant driver with the implant number to carry the dental implants to the light source. In case that surgery requires different implant diameters, there will be more need of driver ready to use. In our invention, the dentist will not require any extra pieces, the implant drivers inside their surgical set will be enough, because according to our invention we are not carrying the implant to another device for light activation, the light source is directly inside the implant box with the dental implant.
- Figure 3 Detailed display of dental implant box with light source and dental implant inside
- the system is an assembly of the following parts: Activation Box Stand Pin(l), Activation Box Stand (2), Orientation lndicator(3), Upper Part of the Multi Socket Unit (4), Lower Part of the Multi Socket Unit(5), Electronic Balast(6), M 4 x 8 Screw(7), M 4 x 6 Screw(8), M 4 x 20 Screw(9), Balast Power Connection Cables(lO), Balast Power Cables(ll), Power Input Socket(12), Activation Box Stand Pin Socket(13), Lamp Stand (14), CCFL UV C (Cold Cathode Fluorescent Lamp)(15), Implant Holder(16), Implant Stand(17), Lamp Stand Pin(18), 0-Ring(Lamp Stand)(19), Cylinder Tube with Reflecting Surface(20), 0-Ring(lmplant Stand)(21), Dental lmplant(22), Lamp Stand Pin Socket(23), Rectangular Socket (24), Cylinder Tube Channel(25), Cylinder Tube Fixing Lug(26), Dental Implant Activ
- CCFL Cold Cathode Fluorescent Lamp
- UV C lamps(15) After having placed lamp stand pin(18) to these two insertion holes, CCFL (Cold Cathode Fluorescent Lamp) lamps(15) will be placed inside the rectangular sockets(24) in order to assure electric current passage.
- CCFL Cold Cathode Fluorescent Lamp
- the implant stand(17) slides through the cylinder tube(20) and gets fixed in a proper position.
- Implant holder(16) gets connected with the implant (22) and both of them are placed on the implant stand(17).
- the implant stand 0-Ring(21) on the implant stand(17) assure the sealing and isolation.
- the dental implant (22) placed on the implant stand(17) will be placed by sliding in through the cylinder tube channel(25).
- dental implant activation box(27) is obtained, where dental implant(22) and CCFL (Cold Cathode Fluorescent Lamp) UV C(15) are sealed and isolated together.
- CCFL Cold Cathode Fluorescent Lamp
- the dental implant activation box(27) will be ready to use by placing it onto the multi socket unit(28).
- the electronic ballast(6) inside the multi socket unit(28) regulates the electric current.
- the ballast power connection cables(lO) on the electronic ballast connects(ll) to the activation box stand pins(l) and complete the circuit. And with the ballast power cables(ll), the electric current will be supplied.
- the circuit will be completed when the dental implant activation box(27) is placed on the activation box stands(2) multi socket unit(28).
- Dental implant activation box(27) is a closed space where dental implant(22) and CCFL (Cold Cathode Fluorescent Lamp) UV C lamps(15) providing surface activation are isolated and sealed together.
- Dental implant activation box(27) is a set up, allowing the dentist to activate the surface of the dental implants(22) by UV C light without breaking the gamma sterilization chain. Since the gamma sterilization will not be broken, the dentist may activate the dental implant(22) multiple times.
- the dental implants(22) can be activated without being exposed to the outer environment, in case of uncertainties, the dentist can activate dental implants(22) more than he/she need and not waste any implant even if the implant is activated but not used. Therefore, the implant not used can be spared for another surgery.
- This invention mainly prevents the implant waste due to the break of gamma sterilization during the surface activation.
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Abstract
The invention is about a package that improves the titanium dental implants (22) physiochemical and biological characteristics with a (UV) light source (15) and the working method of this package. Cylinder tube with (20) placed on the lamp stand (14). By the help of the fixing lug (26) on the lamp stand (14) and with a cylinder tube channel (25) inside the cylinder tube (20), the implant stand (17) slides through the cylinder tube (20) and gets fixed in a proper position. Implant holder(16) gets connected with the implant (22) and both of them are placed on the implant stand (17). The implant stand O-Ring (21) on the implant stand (17) assures the sealing and the isolation. The dental implant (22) placed on the implant stand (17), will be placed by sliding in through the cylinder tube channel (25). By this way, the dental implant activation box (27) is obtained, where dental implant (22) and CCFL (Cold Cathode Fluorescent Lamp) UV C (15) are sealed and isolated together.
Description
DESCRIPTION
DENTAL IMPLANT ACTIVATION BOX USED FOR SURFACE ACTIVATION
WITH UV C
TECHNICAL FIELD
The invention is about a package that improves the titanium dental implant's physiochemical and biological characteristics by the help of a (UV) light source and a renovation on its working method.
CURRENT STATUS
Dental implants have been used for the rehabilitation of total or partial tooth loss, since their invention by Per Ingvar Branemark. Although they can be fabricated from different materials (e.g. peek, ceramics, zirconia), the highly preferred material for production is titanium and its alloys. The first implants that were fabricated had machined surfaces. In time, in order to improve osseointegration properties, many studies have been carried out on for altering surface chemistry and topography. Regarding this, two different processes were applied: a) Additive Techniques: TPS (Titanium Plasma Spray), Hydroxyapatite coating b) Subtractive Technique: Sandblasting with different media (AI2O3, T1O2, CaO) and Acid etching (with different acids, processing times and temperatures)
Nowadays, most of the dental implant companies use the implant material surfaces, which are roughened using subtractive techniques. Titanium, which is used as a dental implant material, is corrosion resistant due to naturally formed T1O2 layer on its surface, biocompatible and has osseointegration dependent load bearing capacity as well. It can make structural and functional bonding between the implant surface and surrounding bone tissue, without forming fibrous tissues.
OSSEOINTEGRATION
In 1950's Branemark observed that titanium placed in a rabbit bone became highly integrated and was hard to remove without fracturing. Following this, it was discovered again by Branemark that titanium could be tolerated by the human body and could be gently integrated to host bone tissue; which is then named as "osseointegration".
Osseointegration (01), can be described as the direct structural and functional bonding between a host hard tissue and the surface of a load-covering implant at the histological level. In the case of bone apposition, without the need of any intervention of soft tissue between the bone-implant interface, it results in the fixation of implants into the host tissue in long-term stability and rigidity Osseointegration is highly required for primary stability of implants and therefore is a very important factor which should be considered prior to following treatments.
MECHANISM OF OSSEOINTEGRATION
During Ol, bone formation proceeds by attachment, settlement, the proliferation of osteoblasts which is followed by their maturation. As a next step, mineralization occurs around the released proteins. Many biological phenomena occur around the bone- implant interface which is identical to bone healing.
The healing process initiates within a few seconds as soon as the blood contacts the surface of the implant. The coagulation cascade is started by thrombocytes, afterwards, phagocytic cells migrate to the inflammatory site as well.
For the removal of the dead cells and the bacterial residues, blood neutrophil levels reaches their maximum in the first couple days of implant surgery. Degradation process is assisted by macrophages, which secrete more cytokines and attracts osteogenic and endothelial progenitors to the healing medium. At the same time, angiogenesis takes place inside the fibrin matrix together with coagulum removal. For the colonization of
osteoblasts and mesenchymal stem cells (MSC), the fibrin matrix takes the role as a scaffold within the very first days.
When osteoprogenitor cells arrive, the formation of the matrix and further mineralization start via contact osteogenesis. During the second week, woven bone starts to remodel on the implant surface and replaced with a lamellar mature bone in the following three months period.
TITANIUM
Researchers have been focused on implant biomaterials in last decades for discovering and developing the most biocompatible materials used as implants reaching high levels of osseointegration and stability. Compared to other metallic biomaterials, it was found that pure titanium and its alloys exhibit extreme mechanical stability, low elasticity modulus, good fatigue strength, and corrosion resistance, as well as their considerable biocompatibility should also be mentioned. Owing to its supreme mechanical and physiochemical characteristics, titanium is the best among all, including stainless steel and chrome-cobalt as long as biocompatibility and clinical preference is considered.
AGING OF TITANIUM
Biological aging can be defined as the physiochemical degradation of the implant surface in relation to time. It is reported that after an appropriate healing period of titanium replacement, osseointegration level is not sufficient as the bone-implant contact stays below 100%.
This situation is related to the carbon deposition, which is unavoidable and is formed by airborne hydrocarbons resulting in hydrocarbon adsorption on the titanium implant surface. This leads to a certain lack of hydrophilicity and loss in surface charge.
Eventually, physiochemical and biological properties are spoiled, e.g. decrease in osteoconductivity, poor osteogenic proliferation, and low absorption of serum proteins.
PHOTOFUNCTIONALIZATION BY UV LIGHT TREATMENT
Photofunctinalization is a process improving physiochemical and biological properties of titanium implants using Ultraviolet (UV) light. Ultraviolet light wavelengths can be classified as UV A (320-400nm) UV B (290-320nm) and UV C (10-290nm). Although hydrocarbons are removed by UV A through inducing T1O2 photocatalysis, UV C irradiation is more effective in the surface hydrocarbon reduction, which than improves hydrophilicity, enhances the adsorption of proteins and cell function, respectively.
The affinity of proteins to the implant surface is improved by photofunctionalization via causing various physiochemical changes on the titanium surface. The process is described as follows: a) Removing unavoidable hydrocarbons adsorbed on the surface b) Increasing the degree of hydrophilicity c) Shifting the surface charge from electronegative to electropositive, which can improve cell adhesion behavior.
HYDROPHILICITY
The wettability of the surfaces by aqueous solutions can be defined as hydrophilicity. When water drops on a hydrophobic surface, the droplet shape is retained, whereas it floats out when the surface is hydrophilic. The angle between the solid surface and the tangent line of the liquid phase at the interface of the solid-liquid phases is called the contact angle. When the contact angle is less than 5 degrees, the surface is "hydrophilic". When the contact angle approaches to 0 degrees, water completely wets the surface, and this is called super hydrophilicity. Nevertheless, it was previously
reported in the literature that independent of the surface topography and surface modification technique, the time-dependent degradation of the osteoconductivity of titanium surface results in a loss in biomechanical strength of Bone-implant-contact (BIC) when compared to a freshly prepared titanium surface. Owing to the gas- permeable packaging of the conventional titanium implants, airborne hydrocarbons adsorbed on the implant surfaces within 4 weeks, converting the hydrophilic surfaces to hydrophobic.
It was reported by Att et al. that titanium surface aging could be attributed to low protein and osteogenic cell adhesion resulted by adsorption of airborne hydrocarbons on the surfaces under ambient conditions. With the increasing amount of hydrocarbons, the zeta potential of the titanium surface shifts from electropositive to electronegative; which prevents negatively charged blood protein and extracellular matrix adhering to the surface. Titanium surface aging gradually induces the hydrophobicity abruptly to a contact angle over 40 degrees in 2 weeks, 60 degrees in 4 weeks, respectively.
HYDROCARBON REMOVAL/UV-OZONE SURFACE TREATMENT
Airborne hydrocarbons are the molecules, which are responsible for the hydrophobicity of TiC surfaces. Hydrocarbons form weak bonds with T1O2 and they adsorb on the surface of the implant. Bolon and Kunz reported that a variety of photoresist polymers can be depolymerized using UV light exposure. They kept the polymer films in a quartz tube filled with oxygen. UV light which was obtained from a medium-pressure mercury lamp generates ozone. In less than one hour of UV treatment, successful depolymerization of polymer thin films were observed, with the release of water and carbon dioxide. By placing a pyrex filter between the UV light and the polymer or, by using nitrogen atmosphere instead, the depolymerization was interrupted. The authors observed that the use of oxygen and UV wavelengths less than 300 nm is extremely effective in the depolymerization process.
Sowell et al. explained the UV cleaning process of airborne hydrocarbons adsorbed on glass and gold surfaces under both air, and vacuum conditions. After 15 hours of UV exposure in air, clean glass surface was maintained. Partial O2 pressure was decreased during cleaning whereas; partial pressures of CO2 and H2O were increased. The authors also indicated that surface cleanliness is maintained by storing under UV exposure.
Vig et al. conducted experiments on the determination of optimal conditions for clean surface production via UV irradiation. The parameters of UV cleaning were well- defined, and it was indicated that, under appropriate conditions, clean surfaces can be obtained in less than one minute by UV/ozone cleaning.
Kume and Nozu showed in their study that T1O2 coated glass sheets could stay clean by rapid decomposing of organic stains from the glass surface. This study concerns photoinduced superhydrophilicity effect due to the removal of hydrophobic organic stains on the surface via the photocatalytic oxidative process.
On the contrary, it was reported by Wang et al that when T1O2 is irradiated by UV, an electron is excited from valance band to the conduction band, creating a hole in the superficial layer. Thus, Ti4+ sites convert to Ti3+, which leads to dissociative water adsorption in order to form basic Ti-OH groups. The corresponding defects most likely influence the chemisorbed water affinity of surrounding sites, bringing out hydrophilic domains.
UV CLEANING MECHANISM
Under UV irradiation, T1O2 exhibits photocatalytic reactivity in order to decompose various organic compounds into CO2 and H2O. For the treatment of naturally formed T1O2 coated implant surfaces, two sorts of UV sources can be used. When UV A irradiation is used, it was shown that the band corresponding to C-C bond drastically decreased, although the 0-C=0 bond slightly decreased in the XPS spectra. Again, with the application of UV A irradiation, the decomposition of carboxylic acids and/or aldehydes were slow by T1O2 photocatalysts; since there was strong interaction
between carboxylic compounds and the Ti4+ sites of the TiC surfaces. These findings clearly show that only by partial decontamination of hydrocarbons can lead to high wettability behavior on titanium surfaces with T1O2 passive layer via UV A light irradiation.
Ogawa et al., however, stated that the strong interaction between bone and titanium implant surface in addition to improved cell attracting properties could not be obtained by UV A irradiation obtained from a high-pressure Hg (mercury) lamp. It can be suggested from the results that the carboxylic compounds and/or ions that are left on the titanium surface inhibit the effective growth of osteoblast cells. The C-C and 0-C=0 can be effectively broken by UV C light. The UV C light irradiation assisted decontamination of carboxylic compounds is suggested to be a photochemical effect.
PRINCIPLE OF UV-OZONE CLEANING
The principles of UV Ozone cleaning can be described as follows:
Organic compounds are decomposed into volatile products (e.g water, carbon dioxide, nitrogen) by UV and strong oxidation during the formation and decomposition of 03.The major wavelengths of the UV irradiation which is obtained from a low-pressure mercury lamp are sorted as 184.9 nm and 253.7 nm. The corresponding wavelengths are emitted in correlation to the lamp envelopes. It should be noted that both wavelengths can be transmitted through pure quartz. As can be absorbed by oxygen, the 184.9 nm wavelength is crucial. This finally leads to generation of ozone. This wavelength can also be absorbed by various organic molecules. Oxygen cannot absorb 253.7 nm radiations. Hence, the corresponding wavelength does not play any role in ozone generation, although it can be absorbed both by most of the organic molecules and ozone. The decomposition of ozone in the UV box or chamber occurs due to ozone absorption.
Therefore, in this presence of both wavelengths (as it is in the UV box or chamber), ozone can be formed and decomposed continuously. Atomic oxygen is formed as an intermediate product during formation and decomposition processes; which is an unstable and a very effective oxidizing agent.
Either the dissociation or the excitation of the organic and other contaminant molecules is caused by the absorption of both 184.9 nm and 253.7 nm wavelengths. Excited or dissociated contaminant molecules react with atomic oxygen and this reaction leads to the cleaning effect of UV/ozone treatment.
WHAT IS UV PHOTOACTIVATION?
Photoactivation is the technique for enhancing the bioactivity of titanium implant surfaces by the use of UV light source without altering its roughness or other morphological structures, but its physicochemical properties. This can be included in neither additive nor subtractive techniques of preparing implant surfaces. Treating with UV is simple, low-cost and can be applied on any kind of implant surfaces for their activation. Titanium which is used in dental implants and orthopedic implants, are coated with a native oxide (T1O2) layer due to its interaction with air. Since these implants are served to the end-users inside gas permeable packages as an ultimate product it is always affected by airborne hydrocarbons from the atmosphere, while it also adsorbs hydrocarbons from water and cleaning solutions during production process. Therefore, adsorption of hydrocarbons on titanium surfaces is unavoidable.
With acid etching method, the carbon content of newly processed implant surface is 19%, whereas, it increases to 58% in 4 weeks and this causes poor bioactivity conditions. This is called biological ageing of titanium. With the UV light treatment, this biological ageing is reversed and the biological activity is increased.
DIFFERENCES BETWEEN NEWLY PROCESSED AND 4-WEEKS AGED TITANIUM
SURFACES
IN-VITRO
Protein adsorption speed and capacity is one of the critical important criteria of biocompatibility for implantable materials. a) Fibronectin adsorption, which is responsible for osteoblast adhesion and proliferation, is observed as 40% less for 4-week aged surfaces when compared to newly processed after 6 hours of incubation. This decrease is observed similarly for 24 hours of incubation.
b) Another protein, which is affected by the aging of titanium, is albumin. Albumin forms 60% of plasma proteins and acts as a carrier of molecules which are poor soluble in water including hormones and calcium. Albumin bound lipids regulate the secretion of calcium and differentiation of osteoblasts on cellular level (cytoplasmic). Adsorption of albumin decreases to 50% on the 4-week aged surfaces compared to newly processed after 6 hours of incubation. Adsorption dramatically decreases after 24 hours of incubation. For instance, the level of albumin adsorption is observed as 20% of newly processed surfaces compared 3-months aged titanium surfaces.
c) Alkalene Phosphatase (ALP) Activity is also negatively affected from the ageing of titanium. ALP which is responsible from the differentiation and mineralization of osteoblasts is found in all cells of human body and especially at high level in bone tissues. Elevated ALP level is an indicator of bone apposition. When compared to newly processed surfaces, ALP activity is 60% decreased on aged surfaces. Calcium deposition is observed as 50% less for 4-week aged surfaces when compared to newly processed.
THE IN-VIVO EFFECTS OF BIOLOGICAL AGEING a) According to the biomechanical push-in test results that were applied on rats ; within the early osseointegration of 2 weeks, the mechanical push-in test values are found to be 37 N, 36 N, 24 N and 16 N respectively for the implants which are acid etched and left for ageing for different time durations (new, 3 days, 2
weeks, 4 weeks). The push-in test values are measured as 49 N for newly processed and 29 N for 4-week aged implants for 4 weeks of osseointegration. b) Periimplant osteogenesis: According to the research on rat femurs, periimplant osteogenesis was morphologically and morphometrically investigated, as new bone formation at high amount is observed around newly processed implant, while, local and partial bone formation is observed to form around 4-week aged implant, within 2 weeks of early healing period. The soft tissue intervention is observed to be high at the interface between newly formed bone and the implant surface in the 4-week aged implants. The soft tissue intervention is rarely observed in the newly processed implants.
Bone Implant Contact (BIC) is measured 2.3 times more in the 2-weeks early healing period and 1.6 times more in 4-weeks healing period in newly processed implants compared to 4-week aged implants.
THE COMPARISON OF NEWLY PROCESSED SURFACE, 4-WEEK AGED SURFACE AND UV TREATED 4-WEEK AGED SURFACE
According to the research of Takahiro Ogawa patented with the file name PCT/US 2009/065816: a) The albumin adsorption of newly processed, 4-week aged and UV treated 4- week aged surfaces is compared. 10% adsorption occurs on the 4-week aged surface whereas this amount increases to 60% for newly processed surface after 2 hours of incubation. 40% less albumin adsorption is measured on 4-week aged surfaces compared to newly processed surfaces for 72 hours of incubation. The level of albumin adsorption is the same for UV treated 4-week aged and newly processed surfaces.
b) When the migrated human mesenchymal stem cells migrated to the environment is considered, the result is: UV treated surface has two times more migrated cells compared to newly processed surface whereas it is four times more compared to 4 week aged surface for three hours incubation. When
attached cells to the surface are considered, the number of cells attached to the 4 weeks old surface was %50 less than the newly processed surface. The UV treated 4 weeks old surface showed %120 higher cell attachment than newly processed surface in 24 hours of incubation
c) When the enhanced in vivo bone-titanium contact is observed, the push in values of the cylindrical implants placed in rat femurs is measured. In early two weeks healing the implants treated with UV gave 3.1 times more push in values than 4 week aged implants and newly processed implants gave 2.8 times more push in value than 4 week aged implants. These differences remained in the late healing period too. The conclusion to draw here is that, treating the implant with UV did not only accelerate the osseointegration but also improved its quality.
The study in which See-Wook et al. carried on the dog jaw bone showed that: when they tried to remove with a reverse torque the implants placed 4 weeks ago, the implant treated with UV required %50 more force than the non-treated one to remove. The BIC (Bone-implant-contact) in the treated implant appeared to be considerably high compared to the untreated ones.
In the same study, it is observed that, in the implant untreated, the bone-soft tissue interaction is more than 20% while the one treated with UV has less than %1.
Bactericidal and anti microbial effect
According the results from the study T. Itabashi, K. Narita et al. carried on the batericidal and antimicrobial effects of the UV treatment are:
After having aged 3 months, the titanium discs prepared for control and test groups were seeded with bacteria and dried for 30 minutes. Later on, they treated the test group with UV C, then they harvested bacteria both from test and untreated discs.
During measurement, they observed that there is no bacterial colonization on the UV treated disc. Hence this showed the bactericidal effect of the UV treated surface.
According to their second test, after the UV treatment, they have performed bacterial seeding on 0/0,5/1/6/24/48 hours and 3/7 days. After 30 minutes of drying, they harvested the bacteria and counted them. The bacterial colonization was dramatically high on non-treated while there is no bacterial colonization on 0 hour sample. Even though there was a time dependent increase of bacterial colonization on the other discs, there was very less bacteria remained colonized compared to the untreated ones.
The conclusion drawn of this study is that treatment with UV shows both bactericidal and antimicrobial effects. This antimicrobial effect endures 7 days.
In the PCT/US2009/065816 patented file, it appears that there is a photoactivation device with trade name TheraBeam Affinity that has been produced by Japanese company Ushio. This is a device containing UV light source, a metallic platform that holds implants, an automatic timer. When switched on, it activates the implants with its UV light source. In order to photoactivate the dental implants with this device, implant box is to be opened which is previously sterilized by gamma radiation and isolated from the outer environment. Then, the implant has to be carried with an implant driver to the platform of the photo device carefully avoiding any contact to the non-sterile devices and places.
After 15 or 20 minutes of activation, the implants has to be taken out from the platform and transferred to the patient's mouth, again by avoiding any contact to the non-sterile devices and places.
When this device is not used, the dentist prepares the proper length and width of implant bed and places the related implant into the implant bed with an implant driver. This is the dentist's routine without the use of device. However in case the dentist
wants to use this device for surface activation, there will be extra steps demanding special care.
Even though Dental Volumetric Tomography (DVT) and Radio Panoramic Graphy (RPG) gives us idea about the diameter and the length of the implant required before surgery, every surgeon knows that unexpected factors may appear during operation. The bone quality, bone structure, anatomical differences and manual skills may change the implants' length and diameters that can be foreseen before the surgery. When this uncertainty about the size and length of implants to be used in the surgery occurs, multiple potential implants should be activated in preparation for the final decision.
For example, if it is planned to place 6 implants to an edentulous jaw, and if there is uncertainty about the length and diameter of 3 implants, it is needed to take out the 3 other potential implants from their box and place to the device. Therefore, in the end of the day, the gamma sterilization chain is to be broken for 9 implants. In this case, 3 implants that will not be used for another patient will be wasted. This kind of application will cause waste of implants and extra cost.
As a consequence, in the chapter named as 7 Tips of Photofunctionalization written by Akiyoshi Funato, Ryhoei Tonotsuka, Hitoshi Murabe and Takahiro Ogawa (A Novel Strategy for Bone Integration and Regeneration: Case Studies), the authors describe the difficulties and disadvantages of the use of this device.
1) If there is an uncertainty about the diameters and length of the implants, the potential implants of different diameter and length should be photofunctionalized before the placement. Therefore, maybe for one implant bed, it needs to functionalize 2 or 3 implants. Moreover, once the implant loses its gamma sterilization when not used, it cannot be repacked to use for another patient.
2) To transfer each implant from their package to the device, one implant driver is needed for each implant. The more uncertainty about implant diameter and length occurs, the more implant driver is needed to transfer them to the device for activation.
For example, for a patient who needs 6 implants, when there is uncertainty about 3 implants, 9 implant drivers will be needed. Therefore, a mess on the table with hand pieces is expected.
3) Once the activation of the surface is complete, the implant and the implant driver must be handled and set with handpiece with caution. It is required to pay attention to not to drop the implant and not to make contact with unsterilized surfaces. Since all this extra caution and care are not within the range of the dentist's routine, it will not be easy to practice and apply.
THE PROBLEMS THAT OUR INNOVATION TRIES TO SOLVE
In current condition, the dental implant is being taken off from its gamma sterilized original package and from its implant stand, then with an implant driver, it is being carried to the light source in order to make the surface activation. Therefore, this procedure obliges the dentist going out of routine.
In our invention, the dentist will keep its routine during surgery. According to our invention, the dentist will not need to carry the dental implant to another device for light source to surface activation anymore. Once the dental implant is produced, it is placed into the dental implant activation box with CCFL (Cold Cathode Fluorescent Lamp) UV C together; then, is sealed and isolated from the outer environment. After gamma sterilization, the dental implant activation box will be delivered to the end user (dentists). Since the implant has a light source inside their box, and since it will be activated with its sealed and isolated condition, the gamma sterilization chain will not be broken, therefore in case of there is uncertainty about diameter and length, the alternative dental implants activated will keep its possibility to be used for another patient. Another problem faced in current condition is that, even if all the implants diameters are the same, the dentist will need the same amount of the implant driver with the implant number to carry the dental implants to the light source. In case that surgery requires different implant diameters, there will be more need of driver ready to use. In our invention, the dentist will not require any extra pieces, the implant
drivers inside their surgical set will be enough, because according to our invention we are not carrying the implant to another device for light activation, the light source is directly inside the implant box with the dental implant.
THE EXPLANATION OF THE INVENTION WITH FIGURES
Figure 1: Detailed display of the invention
Figure 2: Finished display of the invention
Figure 3: Detailed display of dental implant box with light source and dental implant inside
ENUMERATION OF THE PIECES
1- Activation Box Stand Pin
2- Activation Box Stand
3- Orientation Indicator
4- Upper Part of the Multi Socket Unit
5- Lower Part of the Multi Socket Unit
6- Electronic Balast
7- M 4 x 8 Screw
8 M 4 x 6 Screw
9- M 4 x 20 Screw
10- Balast Power Connection Cables
11-Balast Power Cables
12-Power Input Socket
13-Activation Box Stand Pin Socket
14- Lamp Stand
15-CCFL UV C(Cold Cathode Fluorescent Lamp)
16-Implant Holder
17-Implant Stand
18- Lamp Stand Pin
19 0-Ring(Lamp Stand)
20 Cylinder Tube with Reflecting Surface
21 0-Ring(lmplant Stand)
22 Dental Implant
23 Lamp Stand Pin Socket
24 Rectangular Socket
25 Cylinder Tube Channel
26 Cylinder Tube Fixing Lug
27 Dental Implant Activation Box
28 Multi Socket Unit
29 Turn On/Off Button
DETAILED DESCRIPTION AND TECHNICAL FEATURES OF THE INVENTION
The system is an assembly of the following parts: Activation Box Stand Pin(l), Activation Box Stand (2), Orientation lndicator(3), Upper Part of the Multi Socket Unit (4), Lower Part of the Multi Socket Unit(5), Electronic Balast(6), M 4 x 8 Screw(7), M 4 x 6 Screw(8), M 4 x 20 Screw(9), Balast Power Connection Cables(lO), Balast Power Cables(ll), Power Input Socket(12), Activation Box Stand Pin Socket(13), Lamp Stand (14), CCFL UV C (Cold Cathode Fluorescent Lamp)(15), Implant Holder(16), Implant Stand(17), Lamp Stand Pin(18), 0-Ring(Lamp Stand)(19), Cylinder Tube with Reflecting Surface(20), 0-Ring(lmplant Stand)(21), Dental lmplant(22), Lamp Stand Pin Socket(23), Rectangular Socket (24), Cylinder Tube Channel(25), Cylinder Tube Fixing Lug(26), Dental Implant Activation Box(27), Multi Socket Unit(28), Turn On/Off Button(29).
There is a rectangular socket with two pin insertion holes on the lamp stand where CCFL (Cold Cathode Fluorescent Lamp) UV C lamps(15) are mounted. After having placed lamp stand pin(18) to these two insertion holes, CCFL (Cold Cathode Fluorescent Lamp) lamps(15) will be placed inside the rectangular sockets(24) in order to assure electric current passage. Around the lamp stand(14), there are two lamp stands O-
Ring(19) to assure the isolation and sealing. There is a cylinder tube with reflecting surface(20) placed on the lamp stand(14). The cylinder tube with reflecting surface (20) reflects the light of UV C back to the environment. By the help of the fixing lug(26) on the lamp stand(14) and with a cylinder tube channel(25) inside the cylinder tube(20), the implant stand(17) slides through the cylinder tube(20) and gets fixed in a proper position. Implant holder(16) gets connected with the implant (22) and both of them are placed on the implant stand(17). The implant stand 0-Ring(21) on the implant stand(17) assure the sealing and isolation. The dental implant (22) placed on the implant stand(17), will be placed by sliding in through the cylinder tube channel(25). By this way, dental implant activation box(27) is obtained, where dental implant(22) and CCFL (Cold Cathode Fluorescent Lamp) UV C(15) are sealed and isolated together.
The dental implant activation box(27) will be ready to use by placing it onto the multi socket unit(28). The electronic ballast(6) inside the multi socket unit(28) regulates the electric current. The ballast power connection cables(lO) on the electronic ballast connects(ll) to the activation box stand pins(l) and complete the circuit. And with the ballast power cables(ll), the electric current will be supplied. The circuit will be completed when the dental implant activation box(27) is placed on the activation box stands(2) multi socket unit(28).
Dental implant activation box(27) is a closed space where dental implant(22) and CCFL (Cold Cathode Fluorescent Lamp) UV C lamps(15) providing surface activation are isolated and sealed together. Dental implant activation box(27) is a set up, allowing the dentist to activate the surface of the dental implants(22) by UV C light without breaking the gamma sterilization chain. Since the gamma sterilization will not be broken, the dentist may activate the dental implant(22) multiple times. When there is uncertainty about the diameter and length of the implants required on the surgical site, since the dental implants(22) can be activated without being exposed to the outer environment, in case of uncertainties, the dentist can activate dental implants(22) more than he/she
need and not waste any implant even if the implant is activated but not used. Therefore, the implant not used can be spared for another surgery. This invention mainly prevents the implant waste due to the break of gamma sterilization during the surface activation.
REFERENCES
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[5]D.Buser, N.Broggini, M.Wieland, R.K.Schenk, A.J.Denzer, D.L.Cochran, B. Hoffman, A.Lussi and S.G.Steineman Enhanced Bone Apposition to a Chemically Modified SLA Titanium Surface J Dent. Res. 2004
[6]R. Wang, K. Hashimoto, A.Fujishima Light Induced Amphiphilic Surfaces Nature 1997
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[10]Yassir Abdelrahman Hag Elkhidr and Yang Cheng, Achieving superosseointegration: The photofunctionalization effect, Denstistry 2017
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International journal of photoenergy 2008
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[16]Se-Wook Pyo, Young Bum Park, Hong Seeok Moon, Jae-Hoon Lee, Takahiro Ogawa, Photofunctionalization Enhances Bone-Implant Contact, Dynamics of interfacial Osteogenesis, Marginal Bone Seal and Remowal Torque Value of Implants: A Dog Jawbone Study, Implant Dentistry, Vol. 22, No. 6 / 2013
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[18] Jae-Hon Lee, Takahiro Ogawa, The Biological Aging of Titanium Implants, Implant Dentistry, Vol. 21, No.5, 415-421/(2012)
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Claims
Claim 1, The invention is an innovation and a change of its working method of the dental implant box used for surface activation with UV light on the dental implants; dental implant activation box(27), which is a closed and isolated environment, is characterized by the presence of CCFL(Cold Cathode Fluorescent Lamp) UV C(15) and dental implant(22) together.
Claim 2, The invention is an innovation and a change of its working method of the dental implant box used for surface activation with UV light on the dental implants; The dental implant activation box(27) is characterized by its function on the insertion to multi socket unit(28).
Claim 3, The invention is an innovation and a change of its working method of the dental box used for surface activation with UV light on the dental implants; By the help of CCFL(Cold Cathode Fluorescent Lamp) UV C(15), dental implant activation box(27) is set to activate dental implant's(22) surface more than one time without being exposed to outer environment.
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US20130189642A1 (en) * | 2010-09-30 | 2013-07-25 | Ushio Denki Kabushiki Kaisha | Light irradiation device for dental implants |
WO2015192259A1 (en) * | 2014-06-20 | 2015-12-23 | Portela León Francisco José | Device for the delivery and packaging of implants |
KR101675506B1 (en) * | 2015-10-19 | 2016-11-11 | 주식회사 디오 | package for dental implant |
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