WO2008145768A1 - Nueva superficie de implantes metálicos a base de titanio destinados a ser insertados en tejido óseo - Google Patents
Nueva superficie de implantes metálicos a base de titanio destinados a ser insertados en tejido óseo Download PDFInfo
- Publication number
- WO2008145768A1 WO2008145768A1 PCT/ES2007/000335 ES2007000335W WO2008145768A1 WO 2008145768 A1 WO2008145768 A1 WO 2008145768A1 ES 2007000335 W ES2007000335 W ES 2007000335W WO 2008145768 A1 WO2008145768 A1 WO 2008145768A1
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- WIPO (PCT)
- Prior art keywords
- implant
- titanium
- thickness
- acid
- oxide particles
- Prior art date
Links
- 239000007943 implant Substances 0.000 title claims abstract description 86
- 239000010936 titanium Substances 0.000 title claims abstract description 53
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229910052719 titanium Inorganic materials 0.000 title claims abstract description 51
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 31
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 29
- 239000002184 metal Substances 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 claims abstract description 27
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims abstract description 19
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims description 49
- 239000002245 particle Substances 0.000 claims description 30
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 26
- 238000005422 blasting Methods 0.000 claims description 25
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 15
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 229910001928 zirconium oxide Inorganic materials 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 12
- 229910001069 Ti alloy Inorganic materials 0.000 claims description 9
- 239000004053 dental implant Substances 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- 239000000463 material Substances 0.000 description 11
- 238000010883 osseointegration Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
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- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 8
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- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 6
- 238000010306 acid treatment Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 210000000963 osteoblast Anatomy 0.000 description 6
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- 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
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- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 210000002805 bone matrix Anatomy 0.000 description 3
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- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910052726 zirconium Inorganic materials 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
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- 229910052593 corundum Inorganic materials 0.000 description 2
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- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
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- 239000007921 spray Substances 0.000 description 2
- NTMYVTSWQJFCPA-UHFFFAOYSA-N (2-tert-butylpyrimidin-5-yl)oxy-ethoxy-propan-2-yloxy-sulfanylidene-$l^{5}-phosphane;[cyano-(4-fluoro-3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate Chemical compound CCOP(=S)(OC(C)C)OC1=CN=C(C(C)(C)C)N=C1.CC1(C)C(C=C(Cl)Cl)C1C(=O)OC(C#N)C1=CC=C(F)C(OC=2C=CC=CC=2)=C1 NTMYVTSWQJFCPA-UHFFFAOYSA-N 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 229910000838 Al alloy Inorganic materials 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000002354 Edentulous Jaw Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 229910000756 V alloy Inorganic materials 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 239000012984 antibiotic solution Substances 0.000 description 1
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- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
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- 239000001963 growth medium Substances 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
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- 238000011835 investigation Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000002050 maxilla Anatomy 0.000 description 1
- 229910001092 metal group alloy Inorganic materials 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 239000010955 niobium Substances 0.000 description 1
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
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- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
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- 230000003239 periodontal effect Effects 0.000 description 1
- 238000001420 photoelectron spectroscopy Methods 0.000 description 1
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- 238000005498 polishing Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
- 238000005211 surface analysis Methods 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000004506 ultrasonic cleaning Methods 0.000 description 1
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
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
-
- 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
- A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/06—Titanium or titanium alloys
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- the invention relates to the field of metal implants for insertion into bone tissue.
- the invention relates to a metal implant surface that has a good roughness, as well as an optimized chemical composition and thickness that result in a better cellular response and, therefore, in a better implant-bone joint.
- the invention also relates to a process for obtaining said surface, as well as to the metallic implant it presents.
- surface means the surface layer or outermost area of an implant composed mainly of the corresponding metal oxide, whose physical differences are clearly different from those of the solid material of which said implant is composed.
- the methods used in the state of the art to increase the surface roughness of the implant are very diverse, among which the application of a coating on the surface, the blasting of the surface with particles and the chemical attack of the surface should be highlighted.
- the usual methods of coating the surface of the metallic implant consist in applying a metallic layer, usually of titanium, or a ceramic layer, usually of hydroxyapatite, by means of various known techniques such as the spray or "spray" of plasma (Palka, V. et al., "The effect of biological environment on the surface of titanium and plasma-sprayed layer of hydroxylapatite.” Journal of Materials Science: Materials in Medicine (1998) 9, 369-373).
- the chemical attack of the implant surface is carried out using various mineral acids such as hydrofluoric acid, hydrochloric acid, sulfuric acid, etc.
- various mineral acids such as hydrofluoric acid, hydrochloric acid, sulfuric acid, etc.
- a two-stage acid treatment is described which is used to obtain the Osseotite® commercial surface.
- aqueous hydrofluoric acid is used to remove the natural oxide on the metal surface
- a mixture of hydrochloric acid and sulfuric acid is used to obtain a micrometric rough surface.
- EP 1477 141 also from Implant Innovations Inc.
- a variation of this method is described in which a mixture of hydrofluoric acid and hydrochloric acid is used in the second stage to treat alloy implant surfaces Titanium and T ⁇ 6AI4V.
- Buser (Buser et al. 1991, Buser at al. 1998, supra) mentions, among other methods, a shot blasting with medium grain alumina followed by pickling with a mixture of hydrofluoric acid and nitric acid; as well as blasting with coarse-grained alumina followed by a chemical treatment with a mixture of hydrochloric acid and sulfuric acid.
- Cochran (Cochran et al. 1994, supra), employs a shot blasting with fine or coarse grain corundum particles followed by a chemical treatment with hydrochloric acid and sulfuric acid to treat a titanium surface.
- KR 2003007840 describes a shot blast with calcium phosphate particles followed by a treatment with a mixture of hydrochloric acid and sulfuric acid.
- WO 2004/008983 by Astra Tech describes a method of surface treatment of implants that combines blasting with fine and coarse titanium oxide particles, followed by a treatment with hydrofluoric acid.
- the present inventors have discovered that the projection of zirconium oxide particles under pressure to blast the external area of the implants, together with a particular combination of acids for subsequent chemical treatment and a suitable final heat treatment allows obtain surfaces with adequate micrometric roughness, a composition practically free of impurities and a thickness that is approximately three times the thickness of conventional surfaces.
- Said surface in addition, has a good porosity and a morphology very similar to that of the spongy bone, very advantageous characteristics in terms of optimizing the osseointegration and bone anchoring process.
- the method of the present invention that combines these technical characteristics allows to obtain surfaces of titanium-based metal implants with very good osseointegration and cellular response properties. Additionally, such a significant increase in the thickness of the surface layer of titanium oxide implies great advantages in terms of a reduction of the released metal ions, an almost stoichiometric titanium oxide composition, and a greater wettability thereof.
- the present invention is intended to provide a surface of a titanium-based metal implant intended to be inserted into bone tissue comprising substantially pure titanium oxide and having a thickness of 8-50 nm.
- Another object of the invention is to provide a titanium-based metal implant intended to be inserted into bone tissue, which has said surface.
- Another object of the invention is to provide a method to get that surface.
- Figure 1 shows a micrograph (15Ox) of the surface according to the invention.
- Figure 2a shows the roughness in three dimensions of the surface according to the invention obtained by confocal microscopy.
- Figure 2b shows the reconstruction of the apical flat zone sector and the corresponding roughness measurement.
- FIG. 3 shows the spectrum of X-ray dispersive energy (EDS) of the surface according to the invention.
- Figure 4 shows the cell viability at 12, 24 and 72 hours as an indicator of the cytotoxicity of the surface according to the invention (03/136/15) with respect to that of other conventional surfaces.
- Figure 5 shows the alkaline phosphatase activity at 6 days of culture as an indicator of bone matrix production by osteoblasts seeded on the surface according to the invention (03/136/15) with respect to other conventional surfaces .
- the present invention provides a surface of a titanium-based metal implant intended to be inserted into bone tissue comprising substantially pure titanium oxide and having a thickness of 8-50 nm, hereinafter "surface of the invention”.
- the surface of a base implant Titanium is the surface layer or outermost zone thereof composed mainly of titanium oxide.
- the surface of the invention has a thickness of 10-30 nm. In a preferred embodiment, the surface of the invention has a thickness of 15 nm.
- Said thickness which is almost three times the thickness of conventional surfaces, means a greater osseointegration of the implant, in addition to a significant reduction in impurities, as previously indicated.
- the term “substantially pure titanium oxide” refers to the fact that the surface of the invention comprises an almost stoichiometric composition of titanium oxide, of approximately 98% by weight, (percentage measured by XPS, or photoemission spectrometry, after 1 minute of "sputtering", or bombardment with accelerated ions, to eliminate the contamination present in the external area of the surface obtained, which is inherent to the method of analysis, and obtain the actual composition thereof ).
- the surface of the invention has a good micrometric roughness and, therefore, very good osseointegration and cellular response properties.
- the morphology of the treated surface is similar to the trabecular bone, optimized for the onset of bone repair.
- its porosity and roughness characteristics allow the homogenization of the residual tensions, the adhesion and fixation of the initial proteins, as well as the adhesion, proliferation and cell maturation and the stability of the extracellular matrix.
- an implant Titanium-based metal intended to be inserted into bone tissue that has the surface of the invention described previously.
- said metal implant is a titanium or a titanium alloy implant.
- Titanium can be commercially pure titanium, for example.
- the titanium alloy can be any suitable titanium alloy such as the titanium, aluminum and vanadium alloy
- Said titanium-based metal implant is suitable for insertion into bone tissue, which may be a dental, orthopedic implant, etc., depending on the bone tissue in which it is desired to insert.
- said metal implant is a dental implant.
- method of the invention which comprises the following steps:
- (a) is carried out at a pressure of 2-10 atm.
- the projection of the zirconium oxide particles is carried out at a pressure of 6 atm.
- the zirconium oxide particles used in step (a) have a particle size of 25-500 ⁇ m. In a preferred embodiment, said zirconium oxide particles have a particle size of 125 ⁇ m.
- any suitable device can be used, such as a Basic Q ⁇ attro model blasting equipment of the Renfert brand. Said equipment is connected to a pressurized air circuit, which projects the zirconia shot with which the machine is loaded.
- the surface is cleaned by any suitable technique method, such as by applying pressurized air and subsequent ultrasonic cleaning treatment.
- the acid composition used in step (b) comprises 15-50% (v / v) of sulfuric acid and 0.01-1% (v / v) of hydrofluoric acid .
- said acid composition comprises 28.8% (v / v) acid sulfuric acid and 0.024% (v / v) hydrofluoric acid.
- This particular combination of acids produces a particular roughness and morphology that, combined with the surface chemical composition obtained with hardly any impurities, produce an optimal cellular response.
- the chemical treatment of stage (b) is carried out at a temperature of 50-110 0 C for 4-60 min. In a preferred embodiment, it said chemical treatment is carried out at a temperature of 75 0 C for 12 min.
- Standard laboratory tools are used, within an extraction hood (model 9001 -GH air hood of the Cruma brand, for example) to avoid acid vapors.
- the implant is removed from the acid bath, washed to remove the remaining acid, and subsequently cleaned by ultrasound and dried.
- a suitable conventional drying device such as a Renfert brand drying oven can be used.
- step (c) the thermal treatment of step (c) is conducted at a temperature of 285 0 C for 60 min.
- This heat treatment at the indicated temperature and during the stipulated time produces a restructuring of the surface layer of titanium oxide, with an increase in crystallinity and a reduction of impurities,
- said heat treatment increases the thickness of the surface layer of the titanium oxide.
- the titanium exposed to the atmosphere oxidizes and generates a layer of titanium oxide about 5 nanometers thick. This oxide layer protects the rest of the titanium from oxidizing.
- the range of thicknesses obtained by the process of the invention from 8 to 50 nm is acceptable in this regard.
- the heat treatment must be carried out at a temperature sufficient to accelerate the diffusion of atmospheric oxygen in the material, and not so high as to produce oxidation in the visible titanium due to the color change. Therefore, the selected working temperature varies between 200 0 C and 450 0 C.
- the treatment time is the second parameter to be controlled.
- a very short time does not allow the effective diffusion of oxygen.
- a time that is too long produces excessive increases in the thickness of the layer and is not industrializable.
- a reasonable range between these two extremes would be between 15 minutes and 24 hours, depending on the treatment temperature. Therefore, the selected working time varies between 15 and 120 minutes.
- This heat treatment is carried out by conventional means, using a low temperature Memmert model UM-100 oven, for example.
- a surface obtainable by the procedure described previously comprises substantially pure titanium oxide and has a thickness of 8-50 nm, as indicated. In a particular embodiment, said surface has a thickness of 10-30 nm. In a preferred embodiment, said surface has a thickness of 15 nm.
- a titanium-based metal implant is provided to be inserted into bone tissue, which has Ia surface obtainable by the procedure described previously.
- said metal implant is a titanium or a titanium alloy implant.
- said metal implant is a dental implant.
- EXAMPLE 1 Obtaining a titanium dental implant with a surface according to the invention.
- a commercially pure titanium Defcon TSA threaded cylinder-conical endoosse implant was subjected to a projection of 125 ⁇ m zirconia particles at a pressure of 6 atm, placing the outlet nozzle perpendicular to the surface to be treated, at a distance of between 2 and 3 cm After blasting, it was cleaned with pressurized air and subsequently immersed in pure water in ultrasound for 10 minutes. Then, it was dried by compressed air.
- aqueous solution with the following composition was then prepared: 28.8% by volume of sulfuric acid and 0.024% by volume of hydrofluoric acid.
- the beaker with the reagent was deposited in a thermal bath, setting the temperature to be reached by the reagent at 75 ° +/- 2 ° C.
- chemical treatment was carried out by immersion of the previously shot blasting implant in the reagent solution for 12 minutes (+/- 15 seconds). After said treatment, the implant was removed from the acid bath and diluted by stirring for about 15 seconds in two pure water baths consecutively.
- the implant thus treated was subjected to a heat treatment. end at a temperature of 285 0 C (+/- 2O 0 C) for 60 minutes in a low temperature Memmert model UM-100 oven.
- the surface morphology obtained in example 1 was studied by surface micrographs and roughness measurement by confocal microscopy.
- Figure 1 shows a micrograph (15Ox) of said surface where it can be seen that the surface has a very characteristic surface roughness, with roughness values R a (average roughness) of about 1 ⁇ m, characterized by a rounded morphology with sharp external edges and presence of a deep porosity distributed homogeneously, due to the action of the acid attack on the surface.
- R a average roughness
- the 3D roughness measurement was performed with a confocal microscope connected to the PL ⁇ software, developed by the Department of Optics of the Technical University School of Terrassa (Polytechnic University of Catalonia). Measurements were made according to DIN 4768 standard, with a Gaussian cut-off filter of 800 ⁇ m.
- Figure 2a shows the roughness in three dimensions of the surface obtained by this technique.
- Figure 2b shows the reconstruction of the apical flat area sector and the corresponding roughness measurement according to a cross-sectional profile of the surface.
- the roughness values obtained give average values of R a (average roughness) of 1.0 ⁇ m, with a spacing between S m peaks of 12 ⁇ m. These values are close to the values cited as desirable in the bibliography referred to in the previous section.
- EDS X-ray dispersive energy analysis
- XPS photoelectron spectrometry
- This technique allows to determine the quantitative composition of a surface in a thickness of approximately 1 ⁇ m with a high spatial resolution.
- the EDS allows detecting the presence of atoms with an atomic weight between boron and uranium, and quantifying their presence on the studied surface.
- EDS X-ray dispersive energy
- the XPS analyzes were performed by the ESCA and TEM Analysis Unit of the Scientific-Technical Services of the University of Barcelona. The results are shown in Table 1, together with a comparison with XPS analysis cited in the bibliography of several dental implants (Wieland et al., "Measurement and evaluation of the chemical composition and topography of titanium implant surfaces", Bone Engineering, cap .14 (2000) JEDavies eds; Massaro et al., "Comparative investigation of the surface properties of commercial titanium dental implants. Part I: chemical composition”. J Mat Sci: Mat in Medicine (2002) 13: 536-548) .
- Residual% up to 100% is due to the argon detected (not indicated), which is a residue of the XPS measurement process.
- Figure 4 shows the results of the measurement of cell viability at
- Figure 5 shows the results of the measurement of the alkaline phosphatase activity at 6 days of culture of said samples.
- the alkaline phosphatase activity has long been associated with biological calcification.
- the improved expression of this enzyme seems to be necessary before the start of the mineralization of the bone matrix, providing localized enrichment of inorganic phosphate for the nucleation and proliferation of hydroxyapatite crystals, the main component of bone tissue.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dentistry (AREA)
- Ceramic Engineering (AREA)
- Engineering & Computer Science (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
- Dental Prosthetics (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Dental Preparations (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX2009012942A MX2009012942A (es) | 2007-06-01 | 2007-06-07 | Nueva superficie de implantes metalicos a base de titanio destinados a ser insertados en tejido oseo. |
BRPI0721673-4A2A BRPI0721673A2 (pt) | 2007-06-01 | 2007-06-07 | Nova superfície para implantes metálicos à base de titânio a serem inseridos em tecido ósseo |
CA002689319A CA2689319A1 (en) | 2007-06-01 | 2007-06-07 | New surface of titanium-based metal implants to be inserted into bone tissue |
US12/602,495 US20110218645A1 (en) | 2007-06-01 | 2007-06-07 | surface of titanium- based metal implants to be inserted into bone tissue |
JP2010509850A JP2010528694A (ja) | 2007-06-01 | 2007-06-07 | 骨組織中に挿入するチタン系金属充填材の新規な表面 |
EP07788583A EP2168527A4 (en) | 2007-06-01 | 2007-06-07 | NEW SURFACE OF TITANIUM-BASED METAL IMPLANTS FOR INSERTION INTO BONE TISSUE |
CN200780053197A CN101720209A (zh) | 2007-06-01 | 2007-06-07 | 用于插入到骨组织的钛基金属植入物的新型表面 |
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ES200701518A ES2310129B1 (es) | 2007-06-01 | 2007-06-01 | Nueva superficie de implantes metalicos a base de titanio destinados a ser insertado en tejido oseo. |
ESP200701518 | 2007-06-01 |
Publications (1)
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WO2008145768A1 true WO2008145768A1 (es) | 2008-12-04 |
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PCT/ES2007/000335 WO2008145768A1 (es) | 2007-06-01 | 2007-06-07 | Nueva superficie de implantes metálicos a base de titanio destinados a ser insertados en tejido óseo |
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US (1) | US20110218645A1 (es) |
EP (1) | EP2168527A4 (es) |
JP (1) | JP2010528694A (es) |
CN (1) | CN101720209A (es) |
AR (1) | AR068791A1 (es) |
BR (1) | BRPI0721673A2 (es) |
CA (1) | CA2689319A1 (es) |
CL (1) | CL2008001607A1 (es) |
ES (1) | ES2310129B1 (es) |
MX (1) | MX2009012942A (es) |
PE (1) | PE20090760A1 (es) |
RU (1) | RU2435613C2 (es) |
WO (1) | WO2008145768A1 (es) |
Families Citing this family (11)
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ES2315194B1 (es) | 2007-09-10 | 2010-02-26 | Francisco J. GARCIA SABAN | Procedimiento para obtener una nueva superficie de un implante metalico a base de titanio destinado a ser insertado en tejido oseo. |
US8313531B2 (en) * | 2010-03-08 | 2012-11-20 | Hip Innovation Technology Llc | Interlocking reverse hip prosthesis and method |
RU2469744C1 (ru) * | 2011-06-30 | 2012-12-20 | Фикрет Мавлудинович Абдуллаев | Способ создания наноструктурной биоинертной пористой поверхности на титановых имплантатах |
US10687956B2 (en) | 2014-06-17 | 2020-06-23 | Titan Spine, Inc. | Corpectomy implants with roughened bioactive lateral surfaces |
TWI726940B (zh) | 2015-11-20 | 2021-05-11 | 美商泰坦脊柱股份有限公司 | 積層製造整形外科植入物之方法 |
AU2016355581B2 (en) | 2015-11-20 | 2022-09-08 | Titan Spine, Inc. | Processes for additively manufacturing orthopedic implants |
WO2018026449A1 (en) | 2016-08-03 | 2018-02-08 | Titan Spine, Llc | Implant surfaces that enhance osteoinduction |
CN106498397B (zh) * | 2016-11-16 | 2019-04-09 | 中国科学院深圳先进技术研究院 | 一种基于盐蚀的在钛基种植体表面原位构建多级纳米拓扑结构的方法 |
JP2023544553A (ja) * | 2020-09-25 | 2023-10-24 | 北京▲華▼宇▲創▼新科技有限公司 | 多孔質膜を有する骨インプラントおよびその製造方法 |
KR102567524B1 (ko) | 2021-07-14 | 2023-08-16 | 주식회사 유니덴탈 | 임플란트의 잔류 산 제거 방법 |
CN113633438A (zh) * | 2021-08-16 | 2021-11-12 | 宁波慈北医疗器械有限公司 | 一种表面改性人工颅骨修复体的制作方法 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4818559A (en) * | 1985-08-08 | 1989-04-04 | Sumitomo Chemical Company, Limited | Method for producing endosseous implants |
US5603338A (en) | 1994-11-30 | 1997-02-18 | Innovative Implants, Inc. | Implant surface preparation utilizing acid treatment |
US5863201A (en) | 1994-11-30 | 1999-01-26 | Implant Innovations, Inc. | Infection-blocking dental implant |
KR20030007840A (ko) | 2000-06-02 | 2003-01-23 | 스미스클라인 비참 코포레이션 | Il-18을 이용한 및 il-18 조합 제제를 이용한바이러스 질환의 치료 방법 |
US6652765B1 (en) | 1994-11-30 | 2003-11-25 | Implant Innovations, Inc. | Implant surface preparation |
WO2004008983A1 (en) | 2002-07-19 | 2004-01-29 | Astra Tech Ab | An implant and a method for treating an implant surface |
US6689170B1 (en) * | 1997-05-16 | 2004-02-10 | Cecilia Larsson | Implant element |
EP1477141A1 (en) | 2003-05-16 | 2004-11-17 | Implant Innovations, Inc. | Surface treatment process for implants made of titanium alloy |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5307594A (en) * | 1992-12-14 | 1994-05-03 | Zimmer, Inc. | Method for forming textured surfaces on an orthopaedic implant |
DE50310328D1 (de) * | 2003-10-27 | 2008-09-25 | Straumann Holding Ag | Implantat mit einer keramischen Beschichtung |
ATE369812T1 (de) * | 2004-12-23 | 2007-09-15 | Plus Orthopedics Ag | Verfahren zum oberfläche-fertigbearbeiten von knochenimplantaten |
-
2007
- 2007-06-01 ES ES200701518A patent/ES2310129B1/es not_active Expired - Fee Related
- 2007-06-07 CA CA002689319A patent/CA2689319A1/en not_active Abandoned
- 2007-06-07 BR BRPI0721673-4A2A patent/BRPI0721673A2/pt not_active IP Right Cessation
- 2007-06-07 RU RU2009149207/15A patent/RU2435613C2/ru not_active IP Right Cessation
- 2007-06-07 EP EP07788583A patent/EP2168527A4/en not_active Withdrawn
- 2007-06-07 CN CN200780053197A patent/CN101720209A/zh active Pending
- 2007-06-07 WO PCT/ES2007/000335 patent/WO2008145768A1/es active Application Filing
- 2007-06-07 MX MX2009012942A patent/MX2009012942A/es active IP Right Grant
- 2007-06-07 JP JP2010509850A patent/JP2010528694A/ja active Pending
- 2007-06-07 US US12/602,495 patent/US20110218645A1/en not_active Abandoned
-
2008
- 2008-05-30 AR ARP080102276A patent/AR068791A1/es not_active Application Discontinuation
- 2008-05-30 PE PE2008000922A patent/PE20090760A1/es not_active Application Discontinuation
- 2008-06-02 CL CL200801607A patent/CL2008001607A1/es unknown
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4818559A (en) * | 1985-08-08 | 1989-04-04 | Sumitomo Chemical Company, Limited | Method for producing endosseous implants |
US5603338A (en) | 1994-11-30 | 1997-02-18 | Innovative Implants, Inc. | Implant surface preparation utilizing acid treatment |
US5863201A (en) | 1994-11-30 | 1999-01-26 | Implant Innovations, Inc. | Infection-blocking dental implant |
US5876453A (en) | 1994-11-30 | 1999-03-02 | Implant Innovations, Inc. | Implant surface preparation |
US6652765B1 (en) | 1994-11-30 | 2003-11-25 | Implant Innovations, Inc. | Implant surface preparation |
US6689170B1 (en) * | 1997-05-16 | 2004-02-10 | Cecilia Larsson | Implant element |
KR20030007840A (ko) | 2000-06-02 | 2003-01-23 | 스미스클라인 비참 코포레이션 | Il-18을 이용한 및 il-18 조합 제제를 이용한바이러스 질환의 치료 방법 |
WO2004008983A1 (en) | 2002-07-19 | 2004-01-29 | Astra Tech Ab | An implant and a method for treating an implant surface |
EP1477141A1 (en) | 2003-05-16 | 2004-11-17 | Implant Innovations, Inc. | Surface treatment process for implants made of titanium alloy |
Non-Patent Citations (19)
Also Published As
Publication number | Publication date |
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BRPI0721673A2 (pt) | 2014-03-04 |
CA2689319A1 (en) | 2008-12-04 |
RU2435613C2 (ru) | 2011-12-10 |
ES2310129B1 (es) | 2009-10-02 |
AR068791A1 (es) | 2009-12-09 |
MX2009012942A (es) | 2010-02-24 |
CN101720209A (zh) | 2010-06-02 |
JP2010528694A (ja) | 2010-08-26 |
EP2168527A4 (en) | 2012-05-16 |
RU2009149207A (ru) | 2011-07-20 |
ES2310129A1 (es) | 2008-12-16 |
EP2168527A1 (en) | 2010-03-31 |
PE20090760A1 (es) | 2009-07-02 |
US20110218645A1 (en) | 2011-09-08 |
CL2008001607A1 (es) | 2008-07-25 |
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