WO1990008520A1 - BONE TISSUE CALCIFICATION ENHANCING CAlCIUM PHOSPHATE CERAMICS - Google Patents
BONE TISSUE CALCIFICATION ENHANCING CAlCIUM PHOSPHATE CERAMICS Download PDFInfo
- Publication number
- WO1990008520A1 WO1990008520A1 PCT/US1990/000663 US9000663W WO9008520A1 WO 1990008520 A1 WO1990008520 A1 WO 1990008520A1 US 9000663 W US9000663 W US 9000663W WO 9008520 A1 WO9008520 A1 WO 9008520A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- powder
- phosphate
- calcium phosphate
- bone
- hydroxyapatite
- Prior art date
Links
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 43
- 239000004068 calcium phosphate ceramic Substances 0.000 title claims description 31
- 230000002708 enhancing effect Effects 0.000 title claims description 5
- 230000002308 calcification Effects 0.000 title description 13
- 238000000576 coating method Methods 0.000 claims abstract description 75
- 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 claims abstract description 61
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 50
- 239000011248 coating agent Substances 0.000 claims abstract description 37
- 239000000463 material Substances 0.000 claims abstract description 30
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229910052751 metal Inorganic materials 0.000 claims abstract description 25
- 239000002184 metal Substances 0.000 claims abstract description 25
- 239000000919 ceramic Substances 0.000 claims abstract description 24
- 239000001506 calcium phosphate Substances 0.000 claims abstract description 22
- 238000000151 deposition Methods 0.000 claims abstract description 20
- 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 17
- 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 17
- 238000004090 dissolution Methods 0.000 claims abstract description 17
- 229910010293 ceramic material Inorganic materials 0.000 claims abstract description 9
- 239000000843 powder Substances 0.000 claims description 56
- 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 claims description 50
- 239000010936 titanium Substances 0.000 claims description 34
- 239000002245 particle Substances 0.000 claims description 29
- 229910052719 titanium Inorganic materials 0.000 claims description 25
- 239000011575 calcium Substances 0.000 claims description 24
- 239000000758 substrate Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 238000005245 sintering Methods 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 17
- 239000007943 implant Substances 0.000 claims description 16
- 239000000725 suspension Substances 0.000 claims description 16
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 14
- 229910052791 calcium Inorganic materials 0.000 claims description 14
- 238000001962 electrophoresis Methods 0.000 claims description 11
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 11
- 230000002950 deficient Effects 0.000 claims description 10
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 10
- 238000013019 agitation Methods 0.000 claims description 5
- 238000002513 implantation Methods 0.000 claims description 5
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 5
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 230000008468 bone growth Effects 0.000 claims description 3
- 230000008467 tissue growth Effects 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 1
- 238000001652 electrophoretic deposition Methods 0.000 abstract description 13
- 238000005054 agglomeration Methods 0.000 abstract description 5
- 230000002776 aggregation Effects 0.000 abstract description 5
- 229960001714 calcium phosphate Drugs 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 239000000203 mixture Substances 0.000 description 18
- 230000008021 deposition Effects 0.000 description 15
- 238000001354 calcination Methods 0.000 description 14
- 230000009466 transformation Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 9
- 238000005524 ceramic coating Methods 0.000 description 8
- 238000002441 X-ray diffraction Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000005137 deposition process Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000007654 immersion Methods 0.000 description 6
- 241000906034 Orthops Species 0.000 description 5
- 230000000975 bioactive effect Effects 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- 230000011164 ossification Effects 0.000 description 5
- 238000011882 arthroplasty Methods 0.000 description 4
- 239000003462 bioceramic Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 206010065687 Bone loss Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 210000001624 hip Anatomy 0.000 description 3
- -1 hydroxyl ions Chemical class 0.000 description 3
- 238000005470 impregnation Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000007750 plasma spraying Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000009772 tissue formation Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 229910052586 apatite Inorganic materials 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000004513 dentition Anatomy 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000005906 dihydroxylation reaction Methods 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[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 VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000036346 tooth eruption Effects 0.000 description 2
- 238000009489 vacuum treatment Methods 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229910017488 Cu K Inorganic materials 0.000 description 1
- 229910017541 Cu-K Inorganic materials 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102100039384 Huntingtin-associated protein 1 Human genes 0.000 description 1
- 101710140977 Huntingtin-associated protein 1 Proteins 0.000 description 1
- 241000428199 Mustelinae Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 238000010161 Student-Newman-Keuls test Methods 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- 229910000883 Ti6Al4V Inorganic materials 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000005313 bioactive glass Substances 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
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- 238000011049 filling Methods 0.000 description 1
- 238000000705 flame atomic absorption spectrometry Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000004394 hip joint Anatomy 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- ICAKDTKJOYSXGC-UHFFFAOYSA-K lanthanum(iii) chloride Chemical compound Cl[La](Cl)Cl ICAKDTKJOYSXGC-UHFFFAOYSA-K 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000002050 maxilla Anatomy 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- DEQXHPXOGUSHDX-UHFFFAOYSA-N methylaminomethanetriol;hydrochloride Chemical compound Cl.CNC(O)(O)O DEQXHPXOGUSHDX-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000004820 osteoconduction Effects 0.000 description 1
- 230000000278 osteoconductive effect Effects 0.000 description 1
- 230000004819 osteoinduction Effects 0.000 description 1
- 230000001009 osteoporotic effect Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
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- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000009718 spray deposition Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30907—Nets or sleeves applied to surface of prostheses or in cement
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- 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
- A61L27/32—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
- A61F2002/30108—Shapes
- A61F2002/3011—Cross-sections or two-dimensional shapes
- A61F2002/30138—Convex polygonal shapes
- A61F2002/30154—Convex polygonal shapes square
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30907—Nets or sleeves applied to surface of prostheses or in cement
- A61F2002/30909—Nets
- A61F2002/30914—Details of the mesh structure, e.g. disposition of the woven warp and weft wires
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
- A61F2230/0017—Angular shapes
- A61F2230/0021—Angular shapes square
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00395—Coating or prosthesis-covering structure made of metals or of alloys
- A61F2310/00407—Coating made of titanium or of Ti-based alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00592—Coating or prosthesis-covering structure made of ceramics or of ceramic-like compounds
- A61F2310/00796—Coating or prosthesis-covering structure made of a phosphorus-containing compound, e.g. hydroxy(l)apatite
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S623/00—Prosthesis, i.e. artificial body members, parts thereof, or aids and accessories therefor
- Y10S623/92—Method or apparatus for preparing or treating prosthetic
- Y10S623/923—Bone
Definitions
- the present invention relates to materials and processes which enhance bone ingrowth in porous surfaces, such as titanium implants. Specifically, materials and processes are presented which permit calcium phosphate ceramic materials to be uniformly deposited by
- Bone tissue consists of approximately 60-67% by weight of calcium phosphate crystals finely dispersed in a collagenous matrix, and also contains about 10% water.
- cementless fixation can be achieved by using any of three methods: bone tissue ingrowth in porous coatings, bone tissue apposition on undulated, grooved, or surface structured prostheses, and fixation through chemical reaction with a bioactive implant surfaces.
- Cementless fixation methods are not free from limitations. When porous coated devices are used the device is not permanently fixed at the time of surgery. A finite time is needed for bone tissue to develop in the porous coating interstices and eventually create sufficient fixation for patients to use their reconstructed joints fully.
- CPC calcium phosphate ceramics
- Calcium phosphate ceramics although widely known to be bone conductive materials, do not, however, have the property of osteo-induction, since they do not promote bone tissue formation in non-osseous implantation sites.
- a porous stainless steel fiber network was coated with a slip cast CPC lining, and a marked increase of bone ingrowth was observed in comparison to the same porous metal without the CPC lining. This effect was pronounced at 2 and 4 weeks, but had disappeared at 12 weeks, because the slower full ingrowth without CPC lining had achieved the same level of ingrowth as that of the earlier extensive ingrowth caused by the osteoconductive lining.
- the phases and their crystal structure, macro-and micro-porosity in the ceramic film, specific surface area, thickness, size and morphology of the pores and of the porous coating itself, and the chemical characteristics of the underlying metal may have occurred among the various studies.
- the particles will migrate first to the most accessible areas 20 of the metallic device 10, such as the tops of the wires. Further, some particles will be able to cross the potential field created by the wires if the particles are sufficiently far from each of the wires and be deposited on the substrate 30 to which the woven mesh is affixed.
- very few particles will migrate first to the most accessible areas 20 of the metallic device 10, such as the tops of the wires. Further, some particles will be able to cross the potential field created by the wires if the particles are sufficiently far from each of the wires and be deposited on the substrate 30 to which the woven mesh is affixed.
- the present invention provides products and methods for enhancing the calcification phase of bone tissue growth. Since the calcification phase is a rate- limiting step of the reactions leading to bone tissue formation, the enhancement of calcification also enhances overall bone growth rates. Thus, the present invention provides materials and processes whereby calcification in porous coated bone implants is enhanced.
- the size of the particles used to practice the present invention is critical. As particle size is critical.
- the calcium phosphate powder of the present invention uses particles with a mean diameter of about 1 ⁇ 10 -6 to 5 ⁇ 10 -6 meters.
- the small particle size leads to the problem of agglomeration, both in the powdered form prior to mixing in solution and by the formation of
- the deposition process of the present invention discloses optimal ranges for several parameters which must be controlled. Specifically, electric potential gradients between 45-90 V/cm, and most preferably of 90 V/cm are disclosed. Previously, preferably much higher gradients between 105-150 V/cm had been used for flat plate
- the time for depositing layers between 20-80 ⁇ 10 -6 meters by the process disclosed is less than 60 seconds at the highest potential gradient of the range disclosed, i.e., 90 V/cm and using the porous mesh coatings of Figure 1. Such conditions are considered acceptable for most commercial applications.
- the preferred coating created in accordance with the present invention may also be subsequently sintered.
- the small particle size used results in shrinkage occurring during sintering, thereby leading to exposure of the underlying metal if the coating is too thin. For this reason, a minimum thickness for uniform ceramic coatings subsequent to sintering of 5 ⁇ 10 -6 meters and preferably of 20 ⁇ 10 -6 meters is disclosed.
- the coatings achieved by the present invention provide a consistent electrophoretic yield from deposit to deposit, and also provide a great number of coatings for a given suspension bath.
- This advantage provided by the present invention results in a considerable increase in production efficiency and economic viability.
- the solution of the present invention lacks the agglomerations typically present; these large clusters do not remain in suspension and thereby substantially limit the number of films which may be deposited from one suspension. Previously, no more than 3 uniform depositions on flat titanium could be made.
- the presence of agglomerations in the prior art process reduces the amount of smaller particles available for deposition in a given solution concentration by weight, these few small particles are then used rapidly, and the solution must be replaced frequently in order to continue further deposition.
- the present invention also provides novel
- electrophoretic coatings which consist essentially of oxyhydroxyapatite and alpha- and beta-tricalcium phosphate, and which are essentially free of tetracalcium phosphate.
- the calcium phosphate powder used By not heat treating in air (calcination) the calcium phosphate powder used and also by using a calcium-deficient hydroxyapatite with a limited amount of adsorbed water, substantially improved coatings are achieved.
- tetracalcium phosphate is formed. This compound is unwanted since it is much too stable and will therefore not enhance bone
- the present invention avoids the formation of tetracalcium phosphate and obtains oxy- hydroxyapatite, and alpha- and beta-tricalcium phosphate, which is highly desirable. It has also been found that it is preferable that the calcium deficient powder contain less than about 5% by weight of adsorbed water; if the water content is higher, electrophoretic deposition is highly ineffective in the non-aquepous suspension used in the present invention.
- Figure 1 is a top view of a portion of porous metal mesh which has an insufficient coating of calcium phosphate ceramic deposited by electrophoresis using materials and processes other than those disclosed;
- Figure 2 is a cross sectional view of the porous metal mesh of Figure 1.
- Figure 3 is a view of a mesh similar to Figure 1, but coated in accordance with present invention.
- Figure 4 is a cross sectional view of the coated mesh of Figure 3.
- the present invention provides ceramic materials and the process for making them which enhance calcification to a greater degree than any other previously known ceramic coatings.
- HA hydroxyapatite
- beta-tricalcium phosphate coatings or a combination of both. It does so in view of the relatively high stability of the HA or the perceived slow degradability of beta-TCP.
- HA is considered stable and it is desired to be stable since it is used as a coating on dense, non-porous coated prostheses in which the HA coating serves as a permanent attachment vehicle.
- the state-of-the-art also teaches plasma spray deposition. It has now been found, however, that the choice of these materials, by themselves or in combination with plasma spraying is a poor choice. Stable or slowly degrading materials or coatings have been found to be sub-optimal.
- the present invention teaches the use of materials and coating with the highest dissolution rate as measured by the release of calcium.
- the materials of the present invention are unstable Ca-(PO 4 ) compounds that are a microscopic mixture of electrophoretically formed CA-P type materials and not a physical mixture of powders of different Ca-P type
- hydroxyapatite, oxy-hydroxyapatite, alpha- and betatricalcium phosphate do not have a high dissolution rate; however, when formed by electrophoresis and subsequently sintered in a microscopic mixture, the resulting
- dissolution rate increases by ten fold. This result is particularly surprising since the HA, oxy-HA, alpha- and beta-TCP are powders, and it would be expected by those of ordinary skill to have a higher dissolution rate since powders have a much greater exposed surface area than coatings.
- the present invention provides a novel prosthetic surface for implantation in bony tissue comprising a porous titanium substrate uniformly coated with a coating
- Alpha-TCP alpha- tricalcium phosphate
- beta-TCP betatricalcium phosphate
- CPC powders are either obtained commercially or synthesized.
- the HA-1 powder is a "Calcium Phosphate Tribasic" (Merck, Darmstadt, Germany). This powder is identical to the HA-1 disclosed previously, see, Ducheyne, P., Van Raemdonck, W., Heughebaert, J.C., Heughebaert, M., "Structural analysis of hydroxyapatite coatings on titanium", Biomaterials 7 , 97-103 (1986), which is hereby incorporated by reference.
- apatitic-TCP apatitic-TCP
- beta-TCP tricalciumphosphate apatitic-TCP
- the two numbers of HAp refer to two different lots.
- the powders used and some of their characteristics are summarized in Table 1.
- the X-ray diffraction (XRD) patterns may be determined using, for example, a Rigaku diffractometer with Cu-K alpha radiation at 45 kV, 35 mA, a scanning rate of 1o 2 (theta)/min. and a computerized diffractogram analyzer.
- the infrared spectrum is obtained using a Fourier transform infrared spectroscope (FTIR) (Nicolet 5 D ⁇ C). Spectra were recorded on 1% powder-KBr mixtures in the diffuse reflectance operational mode.
- FTIR Fourier transform infrared spectroscope
- the porous coated specimens used to generate the accompanying data were Ti-6A1-4V alloy plates, 3 ⁇ 10 ⁇ 10mm, with a commercial purity (c.p.) Ti, orderly oriented wire mesh pressure sintered as described previously, see, P. Ducheyne, M. Martens, "Orderly oriented wire meshes (OOWM) as porous coatings", supra.
- the wire mesh was a 16 mesh size twill weave of 0.50 mm diameter wire, Id.
- the composition of the Ti alloy plate fell within the
- the CPC coatings were electrophoretically deposited from a 3% suspension of the powders in
- isopropanol A 10 mm distance between the lead anode and the cathodic metal specimen was used.
- the electrophoretic yield on dense or porous coated metal substrates was determined for electrical fields between 60 and 100 V/cm and time of deposition from 10 to 60 sec. Before applying the voltage, the suspensions were ultrasonically stirred in order to break the powder particle clusters. All metal substrates were weighed prior to and subsequent to the deposition process.
- Typical parameters were 925oC, 2 hours, 10 -6 to 10 -7 torr and FTIR characterization studies subsequent to deposition and sintering, if any, were made on either the deposited coatings or scraped off powders respectively.
- solutions was determined first. Specifically, a solution devoid of calcium and phosphate ions, i.e., a 0.05 M tris- (hydroxy)methylaminomethane - HCl buffered solution (pH-7.3 at 37oC), was chosen and both the dissolved calcium and the weight loss due to debonding of the coating as a function of immersion time were measured.
- the CPC coatings were obtained starting from HA-1 powder exclusively. The coatings were deposited at 90 V for 60 sec. A 1 mg/1 ml coating weight to solution volume was used, i.e., specimens with a 10 mg coating were immersed in 10 ml of solution contained in 23 mm diameter polystyrene vials. The vials were placed onto a shaker in a water-jacketed incubator. For each time of immersion four separate specimens were used. As controls, solutions without specimens and
- the amount of calcium eluted from each of the specimens was measured in triplicate by flame atomic absorption spectroscopy (AAS). Standard solutions of 0.1, 0.5, 1, 2, 5, and 10 ⁇ 10 -3 mg/ml of calcium were made from a 1,000 mg/ml stock solution of calcium with 1% by weight of lanthanum chloride. The specific areas of the powders and CPC
- HA-1 is a Ca-deficient, non- stoichiometric apatite, corresponding to the formula Ca 10-x (HPO 4 ) 6 (OH) 2-2x .
- the HAp-1 and -2 has a perfect
- hydroxyapatitic stoichiometry and therefore is used to assess the effects of a departure from stoichiometry associated with HA-1.
- the Ap-TCP powders were used in view of the combination of an apatitic structure with a TCP stoichiometry.
- the infrared spectra prior to and after calcination of HA-1, HAp-1 and TCP further support the X- Ray diffraction identifications.
- a broad band is observed in the 3000 - 3600 cm -1 range which is indicative of the stretching vibration of the hydroxyl ions in the adsorbed water, and peaks seen at 875, 1412 and 1455 cm -1 are due to the presence of carbonate groups.
- the hydroxyl peaks at 630 and 3570 cm -1 observed are small; however, they are considerably more intense after
- the infrared spectrum of the TCP shows it is a poorly crystallized apatic structure prior to heating.
- electrophoretically deposited follows from Table 2. This table summarizes the coating weight for one condition of electrophoresis (100 V/cm for 60 sec.) 1 for all dissimilar powders of the study, i.e., HA-1, HAp-1 and Ap- or beta- TCP. Table 2 also represents the water content and the current density during the electrophoresis. It follows from this table that both HAp-1, non calcined and Ap-TCP, which is also a non-calcined powder, cannot be deposited. The weight of the deposit is virtually zero. Calcination produces, among other effects, the elimination of the adsorbed water. Subsequent to this heat treatment both powders can be deposited, as is indicated by the coating weight.
- the adsorbed water interferes with the electrophoretic transport.
- the HA-1 powder contains some adsorbed water and, as shown in Table 1, it does electrophorectically deposit.
- This critical value is probably about 5%, considering that the non-stoichiometric HA-1 powder can still be deposited with a 4.8% water content. With too high a water content the adsorbed water becomes sufficiently accessible at the particle surface immersed in the alcohol solution and the electric energy is consumed in a hydrolysis reaction and no longer in particle transport.
- Table 3 summarizes the chemical compositions and crystal structures of the CPC powders and coatings for which HA-1 and HAp-1 were the starting powders. For the sake of convenience, some of the as-received
- VT heat treatment in vacuum (10 -7 torr) without underlying Ti substrate (925oC, furnace cooling under vacuum); the subscript
- the XRD pattern indicates it is a highly crystalline apatic structure.
- the analysis of the FTIR spectrum indicates it is an oxyhydroxyapatite material. Specifically the nu-4
- the pure HAp i.e., HAp1-C
- HAp1-C a mixture of oxyhydroxyapatite and tetracalcium phosphate.
- the latter phase is formed because the underlying titanium substrate easily attracts phosphorous. Therefore, with a reduced concentration of P, the Ca to P ratio increases from its initial value of 1.67, eventually resulting in a partial transformation to
- hydroxyapatite This is in particular true when as the starting compound for electrophoresis, vacuum treatment or vacuum sintering a mixture of pure hydroxyapatite and some other compound is used. This can be done by using HA-1 in the calcined condition (HA-1 - C), since this powder is a mixture of pure hydroxyapatite and beta-tricalcium
- the ceramics and coatings of the present invention are generally unstable, do not have substantial amounts of tetracalciumphosphate, and exhibit high
- HA-1 non-calcined
- HA-1, non-calcined is a Ca-deficient hydroxyapatite.
- the average Ca to P ratio of the coating increases from its original value of 1.61. Based upon the experimental observations, the ratio never reaches 1.67 or higher during sintering, since only oxyhydroxyapatite, and beta- and alpha-TCP is
- the XRD patterns of HA-1, AR prior to and/or after electrophoretic are identical.
- HA1 which is a calcium deficient hydroxyapatite (Merck).
- CAP 1 is formed by making a composite of 75% HA1 and 25% poly(lactic acid) (% by weight). The composite is deposited by making a suspension in an easily vaporizable solvent (methylene chloride) and dipping a porous metallic specimen into it.
- CAP 2 is a film formed by electrophoretic deposition. The film is 75 ⁇ 10 -6 meters thick; the deposition process occurred at a potential of 90 V/cm for 60 seconds.
- CAP 3 a sintered material, was formed using CAP 2 material.
- the sintering occurred in a vacuum (10 -6 torr, at 925oC for 2 hours.
- the type, thickness and other parameters associated with each coating is contained in Table 6, as well as the initial in vitro dissolution rate for each coating.
- Tables 4-6 were obtained using rectangular plugs 10 ⁇ 5 ⁇ 5 mm, possessing an orderly oriented cp (commercial purity) Ti mesh surface coated with the three calcium phosphate films described above: CAP 1, CAP 2, and CAP 3; an uncoated plug served as a control.
- In vitro dissolution rates were determined by immersion in 0.05M tris physiologic solutions for periods of time ranging from 5 minutes to 24 hours.
- Table 4 reports the dissolution rates observed.
- the coating formed should be
- CAP 1 strengths were 2.7, 3.3. and 3.6 MPA for the 2, 4 and 6 week time periods.
- CAP 1 strengths were 2.1, 2.8 and 4.2 MPA which were not statistically different from the uncoated mesh.
- CAP 2 strengths were 3.6, 4.8 and 5.2 MPA.
- CAP 3 strengths were 4.1, 5.6 and 6.6 MPA. At 6 weeks, the CAP 3 mesh was significantly stronger than the CAP 2 mesh.
- the CAP 3 coating which has the highest dissolution rate, also promotes the best mechanical bond. This dissolution of the coating acts by providing a local source of ions essential for tissue calcification.
- the CAP 3 coating is also quite uniform and complete, having been deposited in accordance with the preferred processing parameters discussed above (and used for the comparative coatings as well).
- the CAP 1 coating is not acceptable, since it results in lower initial bonding strength compared to the porous metal coating without the ceramic used as a control.
- the CAP 2 coating is acceptable and demonstrates the advantages of using the preferred embodiment coating method.
- CAP 3 films are relatively unstable, having higher dissolution rates which result from the fact that they are essentially free of tetracalcium phosphate, and instead consist essentially of alpha and beta tricalcium phosphate, and oxyhydroxyapatite.
- calcification enhancement materials of the present invention is bone augmentation.
- a press fit prosthesis needs to attract calcified tissue as quickly as possible in those areas where bone is not present. This absence of bone can be the result of surgical destruction or of prior bone trauma.
- loss of bone mass follows from full or partial loss of dentition.
- the bone can be rebuilt with calcification promoting substances. Such rebuilding can be undertaken without, or alteratively with proteins that are derived from bone tissue. Such proteins can be made in larger quantities by genetic engineering techniques if necessary. Such proteins may trigger the formation of the organic matrix of bone in non bone-tissue sites.
- the ceramic coatings of the present invention can be removed from the underlying metallic substrate on which they are formed, and be injected in powdered form or otherwise introduced into proximity with bony tissue, to promote its growth.
Abstract
Improved ceramics which promote bone ingrowth are disclosed. The coating of the present invention consists essentially of oxy-hydroxy-apatite, and alpha- and betatricalcium phosphate. Methods of making and using the ceramics are also disclosed. The present invention uses a microscopically powdered form of calcium-phosphate materials and electrophoretic deposition to create ceramics having significantly higher dissolution rates than previous materials. By agitating the electrophoretic solution, agglomeration is prevented and a uniform coating is achieved. Thus, the present invention presents both improved ceramic materials and novel methods of depositing them uniformly upon metal surfaces, such as titanium wire mesh (10).
Description
BONE TISSUE CALCIFICATION ENHANCING CALCIUM PHOSPHATE CERAMICS
FIELD OF THE INVENTION
The present invention relates to materials and processes which enhance bone ingrowth in porous surfaces, such as titanium implants. Specifically, materials and processes are presented which permit calcium phosphate ceramic materials to be uniformly deposited by
electrophoresis.
BACKGROUND OF THE INVENTION
Bone tissue consists of approximately 60-67% by weight of calcium phosphate crystals finely dispersed in a collagenous matrix, and also contains about 10% water.
Some bone-forming reactions have been described. However, neither the actual sequence nor the specific mechanisms leading to bone formation are fully understood. It is logical, however, to consider bone formation as the result of two major trains of events, i.e., a first one that produces the collagen precursor matrix; the next a sequence of steps that leads to calcification, i.e., the
mineralization of the organic matrix. These two phases are distinct, since it is possible to microscopically
distinguish the calcified tissue from the non-calcified (osteoid) tissue in bone tissue that is being laid down.
Cementless fixation of permanent implants has become a widespread surgical procedure which aids in avoiding some of the late complications of cemented
prosthesis. See, "Total joint replacement arthroplasty without cement", Galante, J.O., guest editor Clin. Orthop. 176. section I, symposium, pages 2-114 (1983); Morscher,
E., "Cementless total hip arthroplasty", Clin. Orthop. 181, 76-91 (1983); Eftekhar, N.S., "Long term results of total hip arthroplasty", Clin. Orthop. 225, 207-217 (1987). In principle, cementless fixation can be achieved by using any of three methods: bone tissue ingrowth in porous coatings, bone tissue apposition on undulated, grooved, or surface structured prostheses, and fixation through chemical reaction with a bioactive implant surfaces. See, Hulbert, S.F., Young, F.A., Mathews, R.S., Klawitter, J.J., Talbert, CD., Stelling, F.H., "Potential of ceramic materials as permanently implantable skeletal prostheses", J. Biomed. Mater. Res. 4., 433-456 (1970); Griss, P., Silber, R.,
Merkle, B. , Haehner, K. , Heimke, G., Krempien, B.,
"Biomechanically induced tissue reactions after Al2O3-ceramic hip joint replacement. Experimental study and early clinical results", J. Biomed. Mater. Res. Symp. No. 7, 519-528 (1976); Hench, L.L., Splinter, R.J., Allen, W.C., Greenlee, T.K., Jr., "Bonding mechanisms at the interface of ceramic prosthetic materials", J. Biomed.
Mater. Res. Symp. 2, 117-141 (1973). Common to these three principles of fixation is the necessity that the
surrounding tissues establish and maintain a bond with the device. This can be contrasted with the cemented
reconstructions of which failure is invariably associated with destruction or resorption of surrounding bone tissue. See, Charnley, J., "Low-friction arthroplasty of the hip", Springer-Verlag, Berlin, Heidelberg, New York (1979);
Ducheyne, P., "The fixation of permanent implants: a functional assessment". Function Behavior of Orthopaedic Biomaterials, Vol. II, CRC Press, Boca Raton, Florida
(1984).
Cementless fixation methods are not free from limitations. When porous coated devices are used the device is not permanently fixed at the time of surgery. A finite time is needed for bone tissue to develop in the porous coating interstices and eventually create sufficient
fixation for patients to use their reconstructed joints fully.
It is known that bioactive materials such as calcium phosphate ceramics (CPC) provide direct bone contact at the implant-bone interface and guide bone formation along their surface. These effects are termed collectively osteoconduction. See, Gross, V., Schmitz, H.J., Strunz, V.,
"Surface Activities of bioactive glass, aluminum oxide, and titanium in a living environment. In: "Bioceramics:
material characteristics versus in vivo behavior", Ed P. Ducheyne, J. Lemons, Ann. N.Y. Acad. Sci., 523 (1988); R. LeGeros et al., "Significance of the porosity and physical chemistry of calcium phosphate ceramics: biodegradation- bioresorption", In: "Bioceramics: material
characteristics versus in vivo behavior",
Ed P. Ducheyne, J. Lemons, Ann. N.Y. Acad. Sci., 523
(1988). This property of bioactive ceramics is
attractive, not only because it may help in averting long term bone tissue resorption, but also because it enhances early bone tissue formation in porous metal coatings such that full weight bearing can be allowed much sooner after surgery. Calcium phosphate ceramics, although widely known to be bone conductive materials, do not, however, have the property of osteo-induction, since they do not promote bone tissue formation in non-osseous implantation sites.
The enhancement of bony ingrowth was first documented with slip cast coatings. Ducheyne, P., Hench, L.L., "Comparison of the skeletal fixation of porous and bioreactive materials", Trans. 1st Mtg. Europ. Soc.
Biomater, p. 2PS, Sept. 1977, Strasbourg; Ducheyne, P., Hench, L.L., Kagan, A., Martens, M. , Mulier, J.C., "The effect of hydroxyapatite impregnation on bonding of porous coated implants". Trans. 5th annual mtg., Soc. Biomat. p. 30 (1979); Ducheyne, P., Hench, L.L., Kagan, A., Martens, M., Burssens, A., Mulier, J.C., "The effect of
hydroxyapatite impregnation on skeletal bonding of porous
coated implants", J. Biomed. Mater. Res. 14., 225-237
(1980). A porous stainless steel fiber network was coated with a slip cast CPC lining, and a marked increase of bone ingrowth was observed in comparison to the same porous metal without the CPC lining. This effect was pronounced at 2 and 4 weeks, but had disappeared at 12 weeks, because the slower full ingrowth without CPC lining had achieved the same level of ingrowth as that of the earlier extensive ingrowth caused by the osteoconductive lining.
Subsequently, the effect was studied mostly with plasma sprayed coatings, by numerous researchers. The studies to date, with the exception of one, have confirmed the beneficial effect of calcium phosphate based ceramic linings. See, J.L. Berry, J.M. Geiger, J.M. Moran, J.S. Skraba, A.S. Greenwald, "use of tricalcium phosphate or electrical stimulation to enhance the bone-porous implant interface", J. Biomed. Mater. Res. 20., 65-77 (1986); H.C. Eschenroeder, R.E. McLaughlin, S.I. Reger, "Enhanced stabilization of porous coated metal implants with
tricalcium phosphate granules", Clin. Orthop. 216. 234-246 (1987); D.P. Rivero, J. Fox, A.K. Skipor, R.M. Urban, J.O. Galante, "Calcium phosphate-coated porous titanium implants for enhanced skeletal fixation", J. Biomed. Mater. Res. 22. 191-202 (1988); M.D. Mayor, J.B. Collier, C.K. Hanes,
"Enhanced early fixation of porous coated implants using tricalcium phosphate". Trans. 32nd ORS, 348 (1986); Cook, S.D., Thomas, K.A., Kay, J.F., Jarcho, M. , "Hydroxyapatite-Coated porous titanium for use as an orthopaedic biologic attachment system", Clin. Orthop. 230, 303-312 (1988); H. Oonishi, T. Sugimoto, H. Ishimaru, E. Tsuji, S. Kushitani, T., Nasbashima, M. Aona, K. Maeda, N. Murata, "Comparison of bone ingrowth into Ti-6Al-4V beads coated and uncoated with hydroxyapatite". Trans. 3rd World Biomat. Conf., Kyoto, p. 584 (1988). Yet, the magnitude of the effect has varied from study to study, and was not as pronounced as in an experiment performed by the present inventor. See, Ducheyne, et al., "The effect of hydroxyapatite
impregnation...", supra. More recently, it has been found that porous titanium, spherical bead coatings, plasma sprayed with two calcium phosphate powders (either
hydroxyapatite or beta-tricalcium phosphate before
spraying) also did not yield a clinically meaningful effect. See, Ducheyne, P., Radin, S., Cuckler, J.M., "Bioactive ceramic coatings on metal: structure property relationships of surfaces and interfaces", "Bioceramics 1988" Ed. H. Oonishi, Ishiyaku Euroamerica, Tokyo (1988 in press).
The variability of the effect among the studies noted suggests materials and processing induced parametric influences. The extensive characterization of some plasma sprayed coatings has unveiled that considerable changes of the physical and chemical characteristics of the ceramic subsequent to the deposition are possible. Specifically, differences in chemical composition, the trace ions
present, the phases and their crystal structure, macro-and micro-porosity in the ceramic film, specific surface area, thickness, size and morphology of the pores and of the porous coating itself, and the chemical characteristics of the underlying metal may have occurred among the various studies.
Much of the prior art teaches the use of plasma spray techniques to form ceramic coating. Limitations of plasma spray coatings include: possible clogging of the surface porosity, thereby obstructing bone tissue ingrowth; difficulty in producing a uniform coating--although the HA can flow at the time of impact, plasma spraying is still very much a line of sight process, thus, it is not possible to coat all surfaces evenly, and certainly not the deeper layers of the coating, or the substrate; and finally if viscous flow is wanted, high temperatures are reached by the powders and uncontrolled, and thus unwanted
transformation reactions can occur. Efforts to avoid these transformation reactions can be successful by minimizing the time of flight. However, a low intensity of viscous
flow will result from this and thus, incomplete coverage of the metal can be the result. Thus, at present, it is difficult to obtain an optimal end-product, however, improved ceramic powders may overcome these limitations and provide useful coatings using plasma spraying techniques.
The search thus continues for the optimal
characteristics of the ceramic and for a process by which calcium phosphate ceramics may be deposited upon porous metal surfaces in a uniform manner and with predictable results. Although it is possible to coat flat plates of metals such as titanium by electrophoretic deposition, actual experiments by the applicants to deposit a uniform ceramic film on porous titanium using the information available prior to the current invention were unsuccessful. Referring to Figure 1 and Figure 2, there is illustrated a portion of a porous metallic device which is comprised of a woven mesh. Analysis of porous metallic devices with failed ceramic coatings showed that the ceramic particles were deposited primarily in the few areas indicated in Figure 1 and Figure 2. It is apparent that only those areas that were well exposed to the flow of particles were covered. During electrophoresis, the particles are
electrically attracted to the metal; with a finite amount of particles in the solution, the particles will migrate first to the most accessible areas 20 of the metallic device 10, such as the tops of the wires. Further, some particles will be able to cross the potential field created by the wires if the particles are sufficiently far from each of the wires and be deposited on the substrate 30 to which the woven mesh is affixed. However, very few
particles actually overcome this combination of attractive forces and adhere to the interstitial areas 15. Thus, the known electrophoretic process to coat flat titanium plates does not provide an adequately coated device.
Therefore, it can be seen that there remains a long felt, yet unfulfilled need for both a material with optimum characteristics and a deposition process which
will allow uniform deposition of ceramic materials in a repeatable and commercially viable manner.
SUMMARY OF THE INVENTION
The present invention provides products and methods for enhancing the calcification phase of bone tissue growth. Since the calcification phase is a rate- limiting step of the reactions leading to bone tissue formation, the enhancement of calcification also enhances overall bone growth rates. Thus, the present invention provides materials and processes whereby calcification in porous coated bone implants is enhanced.
It has now been found that by using powdered calcium phosphate of sufficiently small particle size and of selected compositions, substantially improved coating materials result. Moreover, by using a lower voltage potential, and commensurately, a longer deposition time cycle, uniform calcium phosphate films of acceptable thickness and quality may be electrophoretically deposited. In order to prevent agglomeration of the small particles while in solution, the process of the present invention utilizes ultrasonic agitation during the deposition
process.
The size of the particles used to practice the present invention is critical. As particle size is
decreased, its ability to travel and adhere to the
interstices improves. Also, if the weight concentration of the particles in solution is kept constant, then a larger quantity of particles is available and proportionately, more will remain in suspension and migrate into the
interstices. The calcium phosphate powder of the present invention uses particles with a mean diameter of about 1 × 10-6 to 5 × 10-6 meters. The small particle size leads to the problem of agglomeration, both in the powdered form prior to mixing in solution and by the formation of
clusters in solution. It is necessary therefore, to subject the solution to ultrasonic agitation immediately
upon mixing, and to maintain this agitation during the electrophoretic deposition.
The deposition process of the present invention discloses optimal ranges for several parameters which must be controlled. Specifically, electric potential gradients between 45-90 V/cm, and most preferably of 90 V/cm are disclosed. Previously, preferably much higher gradients between 105-150 V/cm had been used for flat plate
deposition. When the electric potential gradient is reduced, the time of deposition must be increased to achieve a sufficient thickness in the deposited film.
However, the time for depositing layers between 20-80 × 10-6 meters by the process disclosed is less than 60 seconds at the highest potential gradient of the range disclosed, i.e., 90 V/cm and using the porous mesh coatings of Figure 1. Such conditions are considered acceptable for most commercial applications.
The preferred coating created in accordance with the present invention may also be subsequently sintered. The small particle size used results in shrinkage occurring during sintering, thereby leading to exposure of the underlying metal if the coating is too thin. For this reason, a minimum thickness for uniform ceramic coatings subsequent to sintering of 5 × 10-6 meters and preferably of 20 × 10-6 meters is disclosed.
The coatings achieved by the present invention, using ultrasonic agitation during the deposition process, provide a consistent electrophoretic yield from deposit to deposit, and also provide a great number of coatings for a given suspension bath. This advantage provided by the present invention results in a considerable increase in production efficiency and economic viability. The solution of the present invention lacks the agglomerations typically present; these large clusters do not remain in suspension and thereby substantially limit the number of films which may be deposited from one suspension. Previously, no more than 3 uniform depositions on flat titanium could be made.
The presence of agglomerations in the prior art process reduces the amount of smaller particles available for deposition in a given solution concentration by weight, these few small particles are then used rapidly, and the solution must be replaced frequently in order to continue further deposition.
The present invention also provides novel
electrophoretic coatings, which consist essentially of oxyhydroxyapatite and alpha- and beta-tricalcium phosphate, and which are essentially free of tetracalcium phosphate. By not heat treating in air (calcination) the calcium phosphate powder used and also by using a calcium-deficient hydroxyapatite with a limited amount of adsorbed water, substantially improved coatings are achieved. Normally, if calcium deficient hydroxyapatite is calcined prior to electrophoresis and subsequently sintered, tetracalcium phosphate is formed. This compound is unwanted since it is much too stable and will therefore not enhance bone
ingrowth significantly. The present invention avoids the formation of tetracalcium phosphate and obtains oxy- hydroxyapatite, and alpha- and beta-tricalcium phosphate, which is highly desirable. It has also been found that it is preferable that the calcium deficient powder contain less than about 5% by weight of adsorbed water; if the water content is higher, electrophoretic deposition is highly ineffective in the non-aquepous suspension used in the present invention.
It is therefore an object of the present invention to create CPC materials which are useful in hard tissue reconstruction as materials which enhance bone tissue calcification.
It is a specific object of the present invention to provide easily reproducible, porous coated metal devices and which have uniform CPC coatings.
It is another object of the present invention to provide ceramic materials which will enhance bone formation in joint replacement devices.
Other objects will become apparent from the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a top view of a portion of porous metal mesh which has an insufficient coating of calcium phosphate ceramic deposited by electrophoresis using materials and processes other than those disclosed;
Figure 2 is a cross sectional view of the porous metal mesh of Figure 1.
Figure 3 is a view of a mesh similar to Figure 1, but coated in accordance with present invention;
Figure 4 is a cross sectional view of the coated mesh of Figure 3.
DETAILED DESCRIPTION
The present invention provides ceramic materials and the process for making them which enhance calcification to a greater degree than any other previously known ceramic coatings.
The approach taken contradicts the logic and thinking in the field of bioactive ceramics. The state-of- the-art of calcium phosphate ceramic coatings for
enhancement of bone tissue ingrowth teaches the use of either hydroxyapatite (HA) coatings or beta-tricalcium phosphate coatings or a combination of both. It does so in view of the relatively high stability of the HA or the perceived slow degradability of beta-TCP. HA is considered stable and it is desired to be stable since it is used as a coating on dense, non-porous coated prostheses in which the HA coating serves as a permanent attachment vehicle. The state-of-the-art also teaches plasma spray deposition. It has now been found, however, that the choice of these materials, by themselves or in combination with plasma spraying is a poor choice. Stable or slowly degrading materials or coatings have been found to be sub-optimal. Instead, the present invention teaches the use of materials and coating with the highest dissolution rate as measured by the release of calcium.
The materials of the present invention are unstable Ca-(PO4) compounds that are a microscopic mixture of electrophoretically formed CA-P type materials and not a physical mixture of powders of different Ca-P type
materials; in addition, they have a specific surface area which, in the case of coatings, exceeds 1 m2/g. Separately, hydroxyapatite, oxy-hydroxyapatite, alpha- and betatricalcium phosphate do not have a high dissolution rate; however, when formed by electrophoresis and subsequently sintered in a microscopic mixture, the resulting
dissolution rate increases by ten fold. This result is particularly surprising since the HA, oxy-HA, alpha- and beta-TCP are powders, and it would be expected by those of ordinary skill to have a higher dissolution rate since powders have a much greater exposed surface area than coatings.
The present invention provides a novel prosthetic surface for implantation in bony tissue comprising a porous titanium substrate uniformly coated with a coating
consisting essentially of oxyhydroxyapatite, alpha- tricalcium phosphate (hereinafter Alpha-TCP) and betatricalcium phosphate (hereinafter beta-TCP). The porous metal devices that were used to reduce part of the
invention to practice are made using orderly oriented wire mesh (OOWM) porous metal coatings, see P. Ducheyne, M.
Martens, P. De Meester, J.C. Mulier, "Titanium implants with porous structure for bone ingrowth: a general
approach", "Titanium and Its Alloys for Surgical Implants", ed. H.A. Luckey, ASTM, Philadelphia, PA, 1983; P. Ducheyne, M. Martens, "Orderly oriented wire meshes (OOWM) as porous coatings on orthopaedic implants", I Morphology, J. Clin. Materials, 1 59-67, (1986); P. Ducheyne, M. Martens,
"Orderly oriented wire meshes (OOWM) as porous coatings on orthopaedic implants; II: the pore size, interfacial bonding and microstructure after pressure sintering of titanium OOWM", J. Clin. Materials, 1, 91-98 (1986); the method that was used to prepare some of the coatings or
powders of the current invention was electrophoretical deposition of CPC films followed by sintering, see,
Ducheyne, P., Van Raemdonck, W., Heughebaert, J.C.,
Heughebaert, M., "Structural analysis of hydroxyapatite coatings on titanium", Biomaterials 2, 97-103 (1986), which are hereby incorporated by reference.
Referring to Figure 3 and 4, it can be seen that the methods of the present invention result in a ceramic coating which covers substantially all exposed surfaces of the metallic device 10. One of ordinary skill will realize that Figures 2 and 3 are generalized representations, not made to any scale. Thus, the methods of the present invention and the ceramic materials disclosed permit porous surfaces, such as the woven wire mesh shown to be
electrophoretically coated with a calcium phosphate ceramic material.
PREPARATION OF COATINGS
For comparative purposes, a number of different types of coatings were created using the following
procedures. CPC powders are either obtained commercially or synthesized. Referring to Table 1, the HA-1 powder is a "Calcium Phosphate Tribasic" (Merck, Darmstadt, Germany). This powder is identical to the HA-1 disclosed previously, see, Ducheyne, P., Van Raemdonck, W., Heughebaert, J.C., Heughebaert, M., "Structural analysis of hydroxyapatite coatings on titanium", Biomaterials 7 , 97-103 (1986), which is hereby incorporated by reference. Hydroxyapatite HAp-1 and HAp-2, and tricalciumphosphate apatitic-TCP (ap-TCP) and beta-TCP may be synthesized according to procedures disclosed previously, see, Bonel, G., Heughebaert, J.C., Heughebaert, M., Lacout, J.L., Lebugle, A., "Apatitic
Calcium Orthophosphates and related compounds for
biomaterials preparation". In Bioceramics: "Material
Characteristics vs. in vivo behavior", Ed. P. Ducheyne, J. Lemons, Ann. N.Y. Ac. Sci., 523 (1988), which are hereby incorporated by reference. The two numbers of HAp refer to two different lots.
The powders used and some of their characteristics are summarized in Table 1. The X-ray diffraction (XRD) patterns may be determined using, for example, a Rigaku diffractometer with Cu-K alpha radiation at 45 kV, 35 mA, a scanning rate of 1º 2 (theta)/min. and a computerized diffractogram analyzer.
The infrared spectrum is obtained using a Fourier transform infrared spectroscope (FTIR) (Nicolet 5 D×C). Spectra were recorded on 1% powder-KBr mixtures in the diffuse reflectance operational mode.
A calcination, which, however is not wanted or necessary to make the ceramic products of the present invention, typically for 1 hour at 900ºc in air, was performed on some of the powders used for comparison purposes. One of the effects of this step is to
substantially remove adsorbed water.
The porous coated specimens used to generate the accompanying data were Ti-6A1-4V alloy plates, 3 × 10 × 10mm, with a commercial purity (c.p.) Ti, orderly oriented wire mesh pressure sintered as described previously, see, P. Ducheyne, M. Martens, "Orderly oriented wire meshes (OOWM) as porous coatings...", supra. The wire mesh was a 16 mesh size twill weave of 0.50 mm diameter wire, Id. The composition of the Ti alloy plate fell within the
specifications of ASTM standard F-136. Prior to the electrophoretic deposition the metal specimens were
ultrasonically cleaned in acetone, immersed for 10 sec.
into a 2% HF + 20% HNO3 aqueous solution, and subsequently rinsed in distilled water.
The CPC coatings were electrophoretically deposited from a 3% suspension of the powders in
isopropanol. A 10 mm distance between the lead anode and the cathodic metal specimen was used. The electrophoretic yield on dense or porous coated metal substrates was determined for electrical fields between 60 and 100 V/cm and time of deposition from 10 to 60 sec. Before applying the voltage, the suspensions were ultrasonically stirred in
order to break the powder particle clusters. All metal substrates were weighed prior to and subsequent to the deposition process.
Any thermal treatment of the CPC subsequent to electrophoresis, was carried out in vacuum and at
relatively low temperatures, in order to minimize the effect on the mechanical properties of the underlying metal. Typical parameters were 925ºC, 2 hours, 10-6 to 10-7 torr and FTIR characterization studies subsequent to deposition and sintering, if any, were made on either the deposited coatings or scraped off powders respectively.
In view of their intended in vivo use, the assessment of stability in simulated physiological
solutions was determined first. Specifically, a solution devoid of calcium and phosphate ions, i.e., a 0.05 M tris- (hydroxy)methylaminomethane - HCl buffered solution (pH-7.3 at 37ºC), was chosen and both the dissolved calcium and the weight loss due to debonding of the coating as a function of immersion time were measured. The CPC coatings were obtained starting from HA-1 powder exclusively. The coatings were deposited at 90 V for 60 sec. A 1 mg/1 ml coating weight to solution volume was used, i.e., specimens with a 10 mg coating were immersed in 10 ml of solution contained in 23 mm diameter polystyrene vials. The vials were placed onto a shaker in a water-jacketed incubator. For each time of immersion four separate specimens were used. As controls, solutions without specimens and
solutions with as received HA-1 powder were used.
Similarly, four samples were used for each immersion time. At the end of each immersion time, the specimens were dried and weighed immediately.
The amount of calcium eluted from each of the specimens was measured in triplicate by flame atomic absorption spectroscopy (AAS). Standard solutions of 0.1, 0.5, 1, 2, 5, and 10 × 10-3 mg/ml of calcium were made from a 1,000 mg/ml stock solution of calcium with 1% by weight of lanthanum chloride.
The specific areas of the powders and CPC
coatings on porous Ti used were measured by the B.E.T.
technique on a Quantasorb, Quantachrome instrument
(Greenvale, NY). The morphology of the powders, and the coatings prior to and as a result of the immersion tests was analyzed using scanning electron microscopy (Philips SEM 500, Eindhoven, The Netherlands). All powders,
including those used for comparative purposes only and which are not an object of the present invention were prepared for S.E.M. analysis by suspending them
ultrasonically in the isopropanol solution (5 mg/30 ml isopropanlol). A droplet of the suspension subsequently was dripped onto the polished aluminum SEM-specimen holder. This technique allowed the powders to be visualized as particles the way they were in solution, and not as
clusters that these particles usually form.
The characteristics of the various powders, some of which were only used for comparative purposes, are summarized in Table 1. The Ca/P atomic ratio was
determined by X-Ray diffraction. The specific surface area values were either measured before or determined for other syntheses using identical synthesizing procedures.
As indicated in Table 1, the Ca/P ratios of HA-1, HAP-1 and -2, and TCP were 1.61, 1.67, 1.67 and 1.47 respectively. Thus HA-1 is a Ca-deficient, non- stoichiometric apatite, corresponding to the formula Ca10-x (HPO4)6 (OH)2-2x. The HAp-1 and -2 has a perfect
hydroxyapatitic stoichiometry and therefore is used to assess the effects of a departure from stoichiometry associated with HA-1. The Ap-TCP powders were used in view of the combination of an apatitic structure with a TCP stoichiometry. The infrared spectra prior to and after calcination of HA-1, HAp-1 and TCP further support the X- Ray diffraction identifications. A broad band is observed in the 3000 - 3600 cm-1 range which is indicative of the stretching vibration of the hydroxyl ions in the adsorbed water, and peaks seen at 875, 1412 and 1455 cm-1 are due to
the presence of carbonate groups. Prior to calcination, the hydroxyl peaks at 630 and 3570 cm-1 observed are small; however, they are considerably more intense after
calcination. Furthermore, subsequent to calcination of HA-1, two characteristic peaks for beta-TCP were observed: 940 and 970 cm-1. Thus the calcination produces a full
crystallization of the hydroxyapatite and a partial
transformation to beta-TCP in HA-1.
The infrared spectra of HAp-1 indicate that it is a poorly crystallized apatite with a considerable amount of adsorbed water prior to, but a pure hydroxyapatite
subsequent to, calcination. The IR spectrum prior to calcination shows a very small OH peak at 3570 cm-1, a very strong NO3- band at 1390 cm-1 and a broad band indicative of adsorbed water in the 3000 - 3600 cm-1 range. Subsequent to calcination, the OH-peak appears larger, the N03 peak disappeared and the two bands at 1040 and 1090 cm-1 specific for the nu-3 stretching vibrations of the PO4 group in hydroxyapatite have become distinct. Thus, in conjunction with the X-Ray diffraction data, the infrared results indicate that HAp-1, calcined, is a well crystallized stoichiometric anhydrous hydroxyapatite.
The infrared spectrum of the TCP shows it is a poorly crystallized apatic structure prior to heating.
There is a broad band indicative of adsorbed water in the 3000 to 3600 cm-1 range. The subsequent calcination step produces the strong peaks at 940 and 970 cm-1 characteristic of beta-TCP. Yet, there are also traces of beta-C2P2O7 as revealed by the small peaks or shoulders at 570, 725, 1026, 1106, 1187 and 1212 cm-1.
A comparative analysis of the electrophoretic yield, i.e., whether or not CPC powders can be
electrophoretically deposited follows from Table 2. This table summarizes the coating weight for one condition of
electrophoresis (100 V/cm for 60 sec.)1 for all dissimilar powders of the study, i.e., HA-1, HAp-1 and Ap- or beta- TCP. Table 2 also represents the water content and the current density during the electrophoresis. It follows from this table that both HAp-1, non calcined and Ap-TCP, which is also a non-calcined powder, cannot be deposited. The weight of the deposit is virtually zero. Calcination produces, among other effects, the elimination of the adsorbed water. Subsequent to this heat treatment both powders can be deposited, as is indicated by the coating weight. Since irrespective of composition or crystal structure, deposition is both possible or excluded, it would therefore follow from these data that the adsorbed water interferes with the electrophoretic transport. Yet the HA-1 powder contains some adsorbed water and, as shown in Table 1, it does electrophorectically deposit. Thus, there is a critical concentration of adsorbed water above which electrophoretic deposition is not possible. This critical value is probably about 5%, considering that the non-stoichiometric HA-1 powder can still be deposited with a 4.8% water content. With too high a water content the adsorbed water becomes sufficiently accessible at the particle surface immersed in the alcohol solution and the electric energy is consumed in a hydrolysis reaction and no longer in particle transport.
Specific surface areas varied by an order of magnitude among the powders that can be deposited (see Table 1). Therefore, this parameter does not appear to exert a predominant effect. Neither does the morphology of the particles affect the outcome of the electrophoretic deposition process substantially.
HA-1 powder was used to establish the
relationship between the electrophoretic deposition
parameters (time, voltage) and the coating thickness. A 1 The electrical field used was chosen at the time of this experiment, prior to the determination of the optimal ranges disclosed elsewhere.
given thicknesses can be obtained in a shorter time when a higher voltage is applied. Obviously, porous coated surfaces required longer deposition times than smooth titanium specimens for similar deposit thicknesses. A uniform thickness of the deposit in the porous coating cannot be achieved with thin coatings (<5 × 10-3 mm) and with higher voltage gradients (>105 V/cm).
Table 3 summarizes the chemical compositions and crystal structures of the CPC powders and coatings for which HA-1 and HAp-1 were the starting powders. For the sake of convenience, some of the as-received
characteristics reported above also are included in this table. The following symbols are used:
AR: as received
C: Calcination (900ºC, 1 hour, air, furnace cooling)
ED: electrophoretic deposition (90 V/cm, 60 sec.)
VT: heat treatment in vacuum (10-7 torr) without underlying Ti substrate (925ºC, furnace cooling under vacuum); the subscript
indicates the hours at temperature.
VS.: sintering in vacuum (10-7 torr) with an
underlying Ti substrate (925ºC, 2 hours, furnace cooling under vacuum)
When the pure hydroxyapatite is vacuum treated at 925ºC without an underlying Ti substrate the XRD pattern indicates it is a highly crystalline apatic structure. The analysis of the FTIR spectrum then indicates it is an oxyhydroxyapatite material. Specifically the nu-4
vibration of PO4 in the 550-600 cm-1 interval, and the absence of the weak presence of the 3570 cm-1 and 630 cm-1 OH-absorption bands provide strong evidence for the
presence of a partially, if not nearly fully dehydroxylated apatitic structure Ca10 (PO4)6 (OH)2-2y Oy []y with the symbol [] representing a vacancy.
The time of vacuum treatment, i.e., 8 or 24 hours, does not yield a meaningful difference;
qualitatively, the same structures are identified.
When the pure HAp (i.e., HAp1-C) is
electrophoretically deposited onto the titanium substrate, removed from it, and heat treated (without an underlying Ti substrate) the structural findings do not change. That is, the electrophoretic deposition in isopropanol does not affect the structure of the CPC powder.
When the pure HAp (i.e., HAp1-C) is, however, deposited and vacuum sintered onto the underlying titanium substrate, it transforms to a mixture of oxyhydroxyapatite and tetracalcium phosphate. The latter phase is formed because the underlying titanium substrate easily attracts phosphorous. Therefore, with a reduced concentration of P, the Ca to P ratio increases from its initial value of 1.67, eventually resulting in a partial transformation to
tetracalcium phosphate.
The structural and compositional changes that occur in CPC that are not pure hydroxyapatite do not necessarily differ from those occurring in the pure
hydroxyapatite. This is in particular true when as the starting compound for electrophoresis, vacuum treatment or vacuum sintering a mixture of pure hydroxyapatite and some other compound is used. This can be done by using HA-1 in the calcined condition (HA-1 - C), since this powder is a mixture of pure hydroxyapatite and beta-tricalcium
phosphate. Subjecting this powder to the same treatment, i.e., electrophoretic deposition and vacuum sintering, as the pure hydroxyapatite (HAp-1, C), produces the same qualitative transformations: that is, the hydroxyapatite transforms to a mixture of oxyhydroxyapatite and
tetracalcium phosphate. In addition, however, the presence of beta-tricalciumphosphate must be considered; and this compound partially transforms to alpha-tricalciumphosphate.
The ceramics and coatings of the present invention are generally unstable, do not have substantial
amounts of tetracalciumphosphate, and exhibit high
dissolution rates. They consist essentially of
oxyhydroxyapitite, alpha-TCP and beta-TCP. Whereas
sintering the commercially obtained CPC powder HA-1 in the calcined condition on titanium does not produce principally different results from the experimentation with pure hydroxyapatite (HAp-1), the eventual structure with the non-calcined commercial powder HA-1 diverge markedly, however, the mechanisms are still the same. HA-1, non-calcined, is a Ca-deficient hydroxyapatite. When vacuum treated on a titanium substrate, four concurrent effects take place. First, the effect of calcination itself, i.e., transformation of the Calcium deficient hydroxyapatite to a pure hydroxyapatite and beta-tricalcium phosphate mixture; second, the partial dehydroxylation of the hydroxyapatite to form oxyhydroxyapatite; third, the partial
transformation of beta-TCP to alpha-TCP; and fourth, the preferential diffusion of P to the Ti substrate, thereby increasing the Ca to P ratio in the mixture. The first three effects are present in HA-1, AR, VT (i.e., without the underlying metal substrate) and thus the net effect is a transformation to a mixture of oxyhydroxyapatite, beta-and alpha-TCP, as follows from the XRD pattern and FTIR spectrum. Such phase transformation can also be achieved with other processes which subject calcium deficient hydroxyapatite to high temperature and to an atmosphere provoking full or partial dehydroxylation.
With the underlying Ti substrate the average Ca to P ratio of the coating increases from its original value of 1.61. Based upon the experimental observations, the ratio never reaches 1.67 or higher during sintering, since only oxyhydroxyapatite, and beta- and alpha-TCP is
observed. Thus, when the CPC coating has a Ca/P ratio prior to sintering of 1.67, the loss of P leads to a mixture of compounds, with a ratio of 1.67 and 2; when the ratio before sintering is below 1.67, e.g., 1.61 it is possible to still obtain a mixture of compounds with
respective atomic ratios of 1.5 and 1.67 subsequent to vacuum sintering on titanium. One of ordinary skill in the art will realize that the effect of the underlying titanium on the desired phase transformation in the ceramic will occur regardless of the deposition process used, so long as the reaction time is sufficient and no other substances interfere with the phosphorous diffusion.
As was the case for the pure hydroxyapatite, the electrophoretic deposition does not change the
characteristics of the powder: the XRD patterns of HA-1, AR prior to and/or after electrophoretic are identical.
IN VIVO EXPERIMENTS
In order to determine the effects of the various coatings described above on actual bone ingrowth, certain experiments were conducted. The experiments are best understood by referring to the data contained in Tables 4- 6. The process of the present invention was carried out using a starting powder, HA1, which is a calcium deficient hydroxyapatite (Merck). CAP 1 is formed by making a composite of 75% HA1 and 25% poly(lactic acid) (% by weight). The composite is deposited by making a suspension in an easily vaporizable solvent (methylene chloride) and dipping a porous metallic specimen into it. CAP 2 is a film formed by electrophoretic deposition. The film is 75 × 10-6 meters thick; the deposition process occurred at a potential of 90 V/cm for 60 seconds. CAP 3, a sintered material, was formed using CAP 2 material. The sintering occurred in a vacuum (10-6 torr, at 925ºC for 2 hours. The type, thickness and other parameters associated with each coating is contained in Table 6, as well as the initial in vitro dissolution rate for each coating.
The results illustrated in Tables 4-6, were obtained using rectangular plugs 10 × 5 × 5 mm, possessing an orderly oriented cp (commercial purity) Ti mesh surface coated with the three calcium phosphate films described above: CAP 1, CAP 2, and CAP 3; an uncoated plug served as a control. In vitro dissolution rates were determined by
immersion in 0.05M tris physiologic solutions for periods of time ranging from 5 minutes to 24 hours. Table 4 reports the dissolution rates observed. In accordance with the present invention, the coating formed should be
relatively unstable. Dissolution rates are an indication of that instability when exposed to physiologic solutions. Coatings of the present invention should exhibit initial dissolution rates under the experimental conditions
described above in excess of 15 × 10-7 mg/cm2.sec,
preferably about 60 × 10-7 mg/cm2. sec, as indicated for CAP 3 coating described in Table 5.
Thirty adult beagle dogs were equally divided into study periods of 2, 4 and 6 weeks. One of each type plug was press fit into the medial and lateral
supracondylar region of both hind limbs. Each specimen was pull tested at sacrifice to determine the interfacial bonding. The decohesion and shear strengths and the levels of statistical significance among the various material types are contained in Tables 4 and 5. One of each type plug was press fit into the medial and lateral
supracondylar region of both hind limbs according to a predetermined randomized order. Radiographs were taken pre- and post-operatively and at sacrifice. Each implant underwent mechanical pullout testing to determine ultimate shear strength. A randomized block ANOVA followed by a
Student-Newman-Keuls test compared the groups. No implants became infected. On radiographic review, no lucencies were present at the bond/coating interface. Initial dissolution rates for CAP 1, CAP 2, and CAP 3 were 2.7 × 10-7, 5.5 × 10 -7 and 6 × 10-6 mg/cm2s respectively. Ultimate shear strength increased both over time and with increasing dissolution rates (see Table 4) . The uncoated mesh
strengths were 2.7, 3.3. and 3.6 MPA for the 2, 4 and 6 week time periods. CAP 1 strengths were 2.1, 2.8 and 4.2 MPA which were not statistically different from the uncoated mesh. CAP 2 strengths were 3.6, 4.8 and 5.2 MPA.
CAP 3 strengths were 4.1, 5.6 and 6.6 MPA. At 6 weeks, the CAP 3 mesh was significantly stronger than the CAP 2 mesh.
As seen from Tables 4-6, the CAP 3 coating, which has the highest dissolution rate, also promotes the best mechanical bond. This dissolution of the coating acts by providing a local source of ions essential for tissue calcification. The CAP 3 coating is also quite uniform and complete, having been deposited in accordance with the preferred processing parameters discussed above (and used for the comparative coatings as well). The CAP 1 coating is not acceptable, since it results in lower initial bonding strength compared to the porous metal coating without the ceramic used as a control. The CAP 2 coating is acceptable and demonstrates the advantages of using the preferred embodiment coating method.
As seen from the above, superior prosthetic surfaces are achieved by using porous titanium coatings which are uniformly coated with ceramic films of specific composition, under controlled deposition procedures. The resulting CAP 3 films are relatively unstable, having higher dissolution rates which result from the fact that they are essentially free of tetracalcium phosphate, and instead consist essentially of alpha and beta tricalcium phosphate, and oxyhydroxyapatite.
While the present invention has been described in connection with prothesis implantation, other major
applications of the calcification enhancement materials of the present invention is bone augmentation. A press fit prosthesis needs to attract calcified tissue as quickly as possible in those areas where bone is not present. This absence of bone can be the result of surgical destruction or of prior bone trauma. In the mandibula or the maxilla, loss of bone mass follows from full or partial loss of dentition. The bone can be rebuilt with calcification promoting substances. Such rebuilding can be undertaken without, or alteratively with proteins that are derived from bone tissue. Such proteins can be made in larger
quantities by genetic engineering techniques if necessary. Such proteins may trigger the formation of the organic matrix of bone in non bone-tissue sites. Thus, when the underlying pathology is such that the bone metabolism is seriously affected, a trigger is needed, supplemented with a substance that enhances the calcification and the overall rate of bone formation. These instances can be situations of larger mandibular or maxillar bone loss, due either to pathology (cysts), absence of dentition, filling of
extracted tooth root sites or periodontal lesions.
Additional applications for the combined use of biological growth factors and calcium phosphate ceramics are
conditions of traumatic bone loss and the absence of normal healing processes like in non-unions. Yet another
application could be the surgical repair of osteoporotic bone loss and concomitant bone collapse. Thus, those of ordinary skill in the art will recognize that the ceramic coatings of the present invention can be removed from the underlying metallic substrate on which they are formed, and be injected in powdered form or otherwise introduced into proximity with bony tissue, to promote its growth.
Claims
1. A device for implantation in bone tissue, at least a portion of said device having a coating which promotes bone growth, said coating consisting essentially of oxy-hydroxyapatite, and at least one of alpha-tricalcium phosphate and beta-tricalcium phosphate said coating being substantially free of tetracalcium phosphate.
2. The device of claim 1, wherein said device is comprised of a metal.
3. The device of claim 2, wherein said metal is titanium.
4. The device of claim 1, wherein said portion is comprised of a wire mesh.
5. A method of depositing a highly soluble bone tissue activation material upon the porous metallic
substrate surface of a bone implant device, comprising the steps of:
(a) combining a calcium phosphate powder which contains approximately less than about 5% by weight of adsorbed water and a non-aqueous liquid to form a suspension;
(b) agitating said suspension to deglomerate said powder;
(c) immersing the substrate into said suspension;
(d) depositing a calcium phosphate film on said substrate by low voltage gradient electrophoresis to form a uniform coating having a thickness of at least 5 microns which, after implantation, enhances bone tissue growth into said device.
6. The method of claim 5, further comprising the step of:
(e) sintering the calcium phosphate coated porous substrate in a vacuum.
7. The method of claim 6, said sintering being conducted at a vacuum of less than about 10-4 torr and at temperatures between about 800 and 1300 C.
8. The method of claim 7, wherein said porous metallic substrate is comprised of titanium and said sintering is conducted at temperatures below about 975 C.
9. The method of claim 6, wherein said powder is selected and agitated to provide said calcium phosphate powder particles in suspension having diameters between about 0.5 × 10-6 and 10 × 10-6 meters.
10. The method of claim 6, wherein said powder is selected and agitated to provide said calcium phosphate powder particles in suspension having diameters between about 1 × 10-6 and 7 × 10-6 meters.
11. The method of claim 6, wherein said powder is selected and agitated to provide said calcium phosphate powder particles in suspension having diameters between about 1 × 10-6 and 5 × 10-6 meters.
12. The method of claim 6, wherein said electrophoresis is carried out using a voltage gradient between about 45 and 90 volts/cm.
13. The method of claim 6, wherein said film is greater than about 5 × 10-6 meters and less than about 150 × 10-6 meters in thickness.
14. The method of claim 6, wherein said film is greater than about 20 × 10~6 meters and less than about 80 × 10-6 meters in thickness.
15. The method of claim 5, wherein said powder consists essentially of one or more of a powder selected from the group consisting of calcium deficient
hydroxyapatite, hydroxyapatite, and tricalcium phosphate.
16. The method of claim 5, wherein said powder has not been calcinated.
17. The method of claim 6, wherein said porous substrate is comprised of a woven mesh.
18. The method of claim 6, wherein said
agitation is carried out at a frequency greater than about 20,000 Hz.
19. The product of the process of claim 5.
20. The product of the process of claim 6.
21. A method of enhancing the bioactivity of a calcium phosphate ceramic material by avoiding the
formation of tetracalcium phosphate, comprising the steps of:
(a) combining a calcium deficient
hydroxyapatite which has a limited amount of adsorbed water with a non-aqueous liquid to form a suspension;
(b) electrophoretically depositing a calcium phosphate layer on an object; and
(c) sintering said layer.
22. The method of claim 21, wherein said
hydroxyapatite has an adsorbed water content of less than about 5% by weight.
23. A ceramic consisting essentially of oxyhydroxyapatite, and at least one of alpha-tricalcium phosphate and beta-tricalcium phosphate, said ceramic powder being substantially free of tetracalcium phosphate.
24. The ceramic of claim 23, wherein the
diameters of the particles of said powder are between about 1 × 10-6 and 10 × 10-6 meters.
25. A prosthetic surface for promoting bone tissue growth comprised of the ceramic of claim 23.
26. A method to promote bone ingrowth by placing a prosthesis and a bone in close proximity with a ceramic consisting essentially of oxy-hydroxyapatite, and at least one of alpha-tricalcium phosphate and beta-tricalcium phosphate.
27. A calcium phosphate ceramic material for enhancing bone growth, having a dissolution rate when immersed in a tris-physiologic solution of greater than 15 mg/cm2.sec.
Applications Claiming Priority (2)
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US07/307,326 US4990163A (en) | 1989-02-06 | 1989-02-06 | Method of depositing calcium phosphate cermamics for bone tissue calcification enhancement |
US307,326 | 1989-02-06 |
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US5205921A (en) * | 1991-02-04 | 1993-04-27 | Queen's University At Kingston | Method for depositing bioactive coatings on conductive substrates |
JP3007903B2 (en) * | 1991-03-29 | 2000-02-14 | 京セラ株式会社 | Artificial disc |
JP3064470B2 (en) * | 1991-04-19 | 2000-07-12 | 杉郎 大谷 | Artificial prosthetic materials |
JPH0751209B2 (en) * | 1991-06-06 | 1995-06-05 | ベステクス株式会社 | Filter material manufacturing method |
US5242706A (en) * | 1991-07-31 | 1993-09-07 | The United States Of America As Represented By The Secretary Of The Navy | Laser-deposited biocompatible films and methods and apparatuses for producing same |
US5211664A (en) * | 1992-01-14 | 1993-05-18 | Forschungsinstitut, Davos Laboratorium Fur Experimentelle Chirugie | Shell structure for bone replacement |
US5258044A (en) * | 1992-01-30 | 1993-11-02 | Etex Corporation | Electrophoretic deposition of calcium phosphate material on implants |
FR2688139B1 (en) * | 1992-03-06 | 1995-06-23 | Zimmer Sa | NEW COATING FOR PROSTHETIC SYSTEM. |
US5338433A (en) * | 1993-06-17 | 1994-08-16 | Mcdonnell Douglas Corporation | Chromium alloy electrodeposition and surface fixation of calcium phosphate ceramics |
US5482731A (en) * | 1994-04-29 | 1996-01-09 | Centro De Investigacion Y De Estudios Avanzados Del Ipn | Method for bonding a calcium phosphate coating to stainless steels and cobalt base alloys for bioactive fixation of artificial implants |
JP3450920B2 (en) * | 1994-12-26 | 2003-09-29 | 京セラ株式会社 | Method for manufacturing bioprosthesis member |
JPH0956805A (en) * | 1995-08-24 | 1997-03-04 | Millennium Biologics Inc | Improved sintering method for thin film manufacturing of calcium phosphate material |
EP0847376B1 (en) | 1995-09-01 | 2005-02-23 | Millenium Biologix Inc. | An artificial stabilized composition of calcium phosphate phases particularly adapted for supporting bone cell activity |
US6846493B2 (en) * | 1995-09-01 | 2005-01-25 | Millenium Biologix Inc. | Synthetic biomaterial compound of calcium phosphate phases particularly adapted for supporting bone cell activity |
AU3069997A (en) * | 1996-05-01 | 1997-11-19 | Us Biomaterials Corporation | Bioactive ceramics and method of preparing bioactive ceramics |
US6280478B1 (en) * | 1997-03-04 | 2001-08-28 | Implico B.V. | Artefact suitable for use as a bone implant |
AU6946198A (en) * | 1997-04-01 | 1998-10-22 | Cap Biotechnology, Inc. | Calcium phosphate microcarriers and microspheres |
US5990380A (en) * | 1997-10-10 | 1999-11-23 | University Of Florida Research Foundation, Inc. | Percutaneous biofixed medical implants |
ATE427751T1 (en) | 1999-07-08 | 2009-04-15 | Cap Biotechnology Inc | CALCIUM-CONTAINING STRUCTURE AND METHOD FOR THE PRODUCTION AND USE THEREOF |
US6893462B2 (en) * | 2000-01-11 | 2005-05-17 | Regeneration Technologies, Inc. | Soft and calcified tissue implants |
GB2366738B (en) * | 2000-03-10 | 2004-03-03 | Technology Finance Corp | Implant including a body of non-resorbable bioactive material |
US7820191B2 (en) | 2000-04-28 | 2010-10-26 | Skeletal Kinetics, Llc | Calcium phosphate cements prepared from silicate solutions |
US6375935B1 (en) | 2000-04-28 | 2002-04-23 | Brent R. Constantz | Calcium phosphate cements prepared from silicate solutions |
US7713305B2 (en) * | 2000-05-01 | 2010-05-11 | Arthrosurface, Inc. | Articular surface implant |
EP2314257B9 (en) * | 2000-05-01 | 2013-02-27 | ArthroSurface, Inc. | System for joint resurface repair |
US6610067B2 (en) * | 2000-05-01 | 2003-08-26 | Arthrosurface, Incorporated | System and method for joint resurface repair |
US20040230315A1 (en) * | 2000-05-01 | 2004-11-18 | Ek Steven W. | Articular surface implant |
US7163541B2 (en) | 2002-12-03 | 2007-01-16 | Arthrosurface Incorporated | Tibial resurfacing system |
US7678151B2 (en) | 2000-05-01 | 2010-03-16 | Ek Steven W | System and method for joint resurface repair |
US8177841B2 (en) | 2000-05-01 | 2012-05-15 | Arthrosurface Inc. | System and method for joint resurface repair |
US7618462B2 (en) | 2000-05-01 | 2009-11-17 | Arthrosurface Incorporated | System and method for joint resurface repair |
CA2308092C (en) | 2000-05-10 | 2008-10-21 | Partho Sarkar | Production of hollow ceramic membranes by electrophoretic deposition |
US6510694B2 (en) | 2000-07-10 | 2003-01-28 | Lockheed Corp | Net molded tantalum carbide rocket nozzle throat |
CA2429246C (en) * | 2000-08-08 | 2011-06-07 | Vincent Bryan | Implantable joint prosthesis |
US7601174B2 (en) | 2000-08-08 | 2009-10-13 | Warsaw Orthopedic, Inc. | Wear-resistant endoprosthetic devices |
US6558426B1 (en) | 2000-11-28 | 2003-05-06 | Medidea, Llc | Multiple-cam, posterior-stabilized knee prosthesis |
US6827743B2 (en) * | 2001-02-28 | 2004-12-07 | Sdgi Holdings, Inc. | Woven orthopedic implants |
GB0126467D0 (en) * | 2001-11-03 | 2002-01-02 | Accentus Plc | Deposition of coatings on substrates |
US20030220692A1 (en) * | 2002-02-09 | 2003-11-27 | Shapiro Irving M. | Preparations of nucleus pulposus cells and methods for their generation, identification, and use |
US20040053197A1 (en) * | 2002-09-16 | 2004-03-18 | Zoran Minevski | Biocompatible implants |
US20060147332A1 (en) | 2004-12-30 | 2006-07-06 | Howmedica Osteonics Corp. | Laser-produced porous structure |
DE60300277T2 (en) | 2002-11-08 | 2006-01-12 | Howmedica Osteonics Corp. | Laser generated porous surface |
US7901408B2 (en) * | 2002-12-03 | 2011-03-08 | Arthrosurface, Inc. | System and method for retrograde procedure |
US8388624B2 (en) | 2003-02-24 | 2013-03-05 | Arthrosurface Incorporated | Trochlear resurfacing system and method |
US7067169B2 (en) * | 2003-06-04 | 2006-06-27 | Chemat Technology Inc. | Coated implants and methods of coating |
US20040250730A1 (en) * | 2003-06-12 | 2004-12-16 | David Delaney | Calcium phosphate cements prepared from silicate-phosphate solutions |
US7306786B2 (en) * | 2003-07-28 | 2007-12-11 | Skeletal Kinetics, Llc | Calcium phosphate cements comprising a water-soluble contrast agent |
US7261718B2 (en) * | 2003-09-11 | 2007-08-28 | Skeletal Kinetics Llc | Use of vibration with polymeric bone cements |
US7261717B2 (en) * | 2003-09-11 | 2007-08-28 | Skeletal Kinetics Llc | Methods and devices for delivering orthopedic cements to a target bone site |
US7252833B2 (en) | 2003-11-18 | 2007-08-07 | Skeletal Kinetics, Llc | Calcium phosphate cements comprising an osteoclastogenic agent |
AU2004293042A1 (en) | 2003-11-20 | 2005-06-09 | Arthrosurface, Inc. | Retrograde delivery of resurfacing devices |
US7951163B2 (en) | 2003-11-20 | 2011-05-31 | Arthrosurface, Inc. | Retrograde excision system and apparatus |
EP1845890A4 (en) * | 2003-11-20 | 2010-06-09 | Arthrosurface Inc | System and method for retrograde procedure |
US9707024B2 (en) | 2004-03-09 | 2017-07-18 | Skeletal Kinetics, Llc | Use of vibration in composite fixation |
US8118812B2 (en) | 2004-03-09 | 2012-02-21 | Skeletal Kinetics, Llc | Use of vibration in composite fixation |
US20050257714A1 (en) * | 2004-05-20 | 2005-11-24 | Constantz Brent R | Orthopedic cements comprising a barium apatite contrast agent |
US7252841B2 (en) * | 2004-05-20 | 2007-08-07 | Skeletal Kinetics, Llc | Rapid setting calcium phosphate cements |
EP1765201A4 (en) | 2004-06-28 | 2013-01-23 | Arthrosurface Inc | System for articular surface replacement |
US7175858B2 (en) | 2004-07-26 | 2007-02-13 | Skeletal Kinetics Llc | Calcium phosphate cements and methods for using the same |
US7828853B2 (en) * | 2004-11-22 | 2010-11-09 | Arthrosurface, Inc. | Articular surface implant and delivery system |
US8470038B2 (en) * | 2005-03-04 | 2013-06-25 | Rti Biologics, Inc. | Adjustable and fixed assembled bone-tendon-bone graft |
US7727278B2 (en) * | 2005-03-04 | 2010-06-01 | Rti Biologics, Inc. | Self fixing assembled bone-tendon-bone graft |
US7763071B2 (en) | 2005-03-04 | 2010-07-27 | Rti Biologics, Inc. | Bone block assemblies and their use in assembled bone-tendon-bone grafts |
US7763072B2 (en) | 2005-03-04 | 2010-07-27 | Rti Biologics, Inc. | Intermediate bone block and its use in bone block assemblies and assembled bone-tendon-bone grafts |
CA2617217A1 (en) * | 2005-07-29 | 2007-02-08 | Arthrosurface, Inc. | System and method for articular surface repair |
CN103349793B (en) | 2005-09-09 | 2016-02-10 | 阿格诺沃斯健康关爱公司 | Composite bone graft substitute cement and the goods obtained by it |
US8025903B2 (en) * | 2005-09-09 | 2011-09-27 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
EP1962914B1 (en) * | 2005-11-14 | 2019-02-27 | Biomet 3i, LLC | Deposition of discrete nanoparticles on an implant surface |
US8728387B2 (en) | 2005-12-06 | 2014-05-20 | Howmedica Osteonics Corp. | Laser-produced porous surface |
CA2572095C (en) | 2005-12-30 | 2009-12-08 | Howmedica Osteonics Corp. | Laser-produced implants |
US8486073B2 (en) * | 2006-02-23 | 2013-07-16 | Picodeon Ltd Oy | Coating on a medical substrate and a coated medical product |
US20090092943A1 (en) * | 2006-03-06 | 2009-04-09 | Shoshana Tamir | Method for manufacturing metal with ceramic coating |
AU2007275343A1 (en) * | 2006-07-17 | 2008-01-24 | Arthrosurface Incorporated | System and method for tissue resection |
US8147861B2 (en) | 2006-08-15 | 2012-04-03 | Howmedica Osteonics Corp. | Antimicrobial implant |
DE102006047663A1 (en) * | 2006-09-29 | 2008-04-03 | Aesculap Ag & Co. Kg | Augmentation component for bone implant is constructed on bone implant from connected bridges that form cavities between them of dimensions between 0.5 and 6 mm |
AU2007332787A1 (en) | 2006-12-11 | 2008-06-19 | Arthrosurface Incorporated | Retrograde resection apparatus and method |
US20080317807A1 (en) * | 2007-06-22 | 2008-12-25 | The University Of Hong Kong | Strontium fortified calcium nano-and microparticle compositions and methods of making and using thereof |
JP5509073B2 (en) | 2007-07-12 | 2014-06-04 | ディスクジェニクス | Human disc tissue |
WO2009014718A1 (en) * | 2007-07-24 | 2009-01-29 | Porex Corporation | Porous laser sintered articles |
US20110035018A1 (en) * | 2007-09-25 | 2011-02-10 | Depuy Products, Inc. | Prosthesis with composite component |
US8632600B2 (en) * | 2007-09-25 | 2014-01-21 | Depuy (Ireland) | Prosthesis with modular extensions |
US8128703B2 (en) * | 2007-09-28 | 2012-03-06 | Depuy Products, Inc. | Fixed-bearing knee prosthesis having interchangeable components |
US8715359B2 (en) | 2009-10-30 | 2014-05-06 | Depuy (Ireland) | Prosthesis for cemented fixation and method for making the prosthesis |
US20110035017A1 (en) * | 2007-09-25 | 2011-02-10 | Depuy Products, Inc. | Prosthesis with cut-off pegs and surgical method |
US9204967B2 (en) | 2007-09-28 | 2015-12-08 | Depuy (Ireland) | Fixed-bearing knee prosthesis having interchangeable components |
EP2240116B1 (en) * | 2008-01-28 | 2015-07-01 | Biomet 3I, LLC | Implant surface with increased hydrophilicity |
EP2262448A4 (en) | 2008-03-03 | 2014-03-26 | Arthrosurface Inc | Bone resurfacing system and method |
US8828086B2 (en) | 2008-06-30 | 2014-09-09 | Depuy (Ireland) | Orthopaedic femoral component having controlled condylar curvature |
US8187335B2 (en) | 2008-06-30 | 2012-05-29 | Depuy Products, Inc. | Posterior stabilized orthopaedic knee prosthesis having controlled condylar curvature |
US9119723B2 (en) | 2008-06-30 | 2015-09-01 | Depuy (Ireland) | Posterior stabilized orthopaedic prosthesis assembly |
US8236061B2 (en) * | 2008-06-30 | 2012-08-07 | Depuy Products, Inc. | Orthopaedic knee prosthesis having controlled condylar curvature |
US8192498B2 (en) | 2008-06-30 | 2012-06-05 | Depuy Products, Inc. | Posterior cructiate-retaining orthopaedic knee prosthesis having controlled condylar curvature |
US8206451B2 (en) | 2008-06-30 | 2012-06-26 | Depuy Products, Inc. | Posterior stabilized orthopaedic prosthesis |
US9168145B2 (en) | 2008-06-30 | 2015-10-27 | Depuy (Ireland) | Posterior stabilized orthopaedic knee prosthesis having controlled condylar curvature |
US8268383B2 (en) * | 2008-09-22 | 2012-09-18 | Depuy Products, Inc. | Medical implant and production thereof |
GB0821927D0 (en) * | 2008-12-01 | 2009-01-07 | Ucl Business Plc | Article and method of surface treatment of an article |
US20100268227A1 (en) * | 2009-04-15 | 2010-10-21 | Depuy Products, Inc. | Methods and Devices for Bone Attachment |
US8696759B2 (en) * | 2009-04-15 | 2014-04-15 | DePuy Synthes Products, LLC | Methods and devices for implants with calcium phosphate |
US10945743B2 (en) | 2009-04-17 | 2021-03-16 | Arthrosurface Incorporated | Glenoid repair system and methods of use thereof |
CA3064646C (en) * | 2009-04-17 | 2023-01-03 | Arthrosurface Incorporated | Glenoid resurfacing system and method |
US9662126B2 (en) * | 2009-04-17 | 2017-05-30 | Arthrosurface Incorporated | Glenoid resurfacing system and method |
US20120093909A1 (en) * | 2009-06-17 | 2012-04-19 | Ahmed El-Ghannam | Ceramic Coatings and Applications Thereof |
US9011547B2 (en) * | 2010-01-21 | 2015-04-21 | Depuy (Ireland) | Knee prosthesis system |
US8475536B2 (en) * | 2010-01-29 | 2013-07-02 | DePuy Synthes Products, LLC | Methods and devices for implants with improved cement adhesion |
US8673018B2 (en) * | 2010-02-05 | 2014-03-18 | AMx Tek LLC | Methods of using water-soluble inorganic compounds for implants |
BR112012022482A2 (en) | 2010-03-05 | 2016-07-19 | Arthrosurface Inc | tibial surface recomposition system and method. |
US8641418B2 (en) | 2010-03-29 | 2014-02-04 | Biomet 3I, Llc | Titanium nano-scale etching on an implant surface |
CN103221000A (en) | 2010-11-18 | 2013-07-24 | 捷迈有限公司 | Resistance welding a porous metal layer to a metal substrate |
US10427235B2 (en) | 2010-11-18 | 2019-10-01 | Zimmer, Inc. | Resistance welding a porous metal layer to a metal substrate |
US9066716B2 (en) | 2011-03-30 | 2015-06-30 | Arthrosurface Incorporated | Suture coil and suture sheath for tissue repair |
US20130165982A1 (en) | 2011-12-22 | 2013-06-27 | Arthrosurface Incorporated | System and Method for Bone Fixation |
US9364896B2 (en) | 2012-02-07 | 2016-06-14 | Medical Modeling Inc. | Fabrication of hybrid solid-porous medical implantable devices with electron beam melting technology |
ES2671740T3 (en) | 2012-03-20 | 2018-06-08 | Biomet 3I, Llc | Treatment surface for an implant surface |
US9135374B2 (en) | 2012-04-06 | 2015-09-15 | Howmedica Osteonics Corp. | Surface modified unit cell lattice structures for optimized secure freeform fabrication |
US9180010B2 (en) | 2012-04-06 | 2015-11-10 | Howmedica Osteonics Corp. | Surface modified unit cell lattice structures for optimized secure freeform fabrication |
DE112013003358T5 (en) | 2012-07-03 | 2015-03-19 | Arthrosurface, Inc. | System and procedure for joint surface replacement and repair |
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US9492200B2 (en) | 2013-04-16 | 2016-11-15 | Arthrosurface Incorporated | Suture system and method |
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US11298747B2 (en) | 2017-05-18 | 2022-04-12 | Howmedica Osteonics Corp. | High fatigue strength porous structure |
US11628517B2 (en) | 2017-06-15 | 2023-04-18 | Howmedica Osteonics Corp. | Porous structures produced by additive layer manufacturing |
CA3108761A1 (en) | 2017-08-04 | 2019-02-07 | Arthrosurface Incorporated | Multicomponent articular surface implant |
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WO2020186099A1 (en) | 2019-03-12 | 2020-09-17 | Arthrosurface Incorporated | Humeral and glenoid articular surface implant systems and methods |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4308064A (en) * | 1978-10-19 | 1981-12-29 | Ngk Spark Plugs Co., Ltd. | Phosphate of calcium ceramics |
US4863475A (en) * | 1984-08-31 | 1989-09-05 | Zimmer, Inc. | Implant and method for production thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2484246A1 (en) * | 1980-06-17 | 1981-12-18 | Europ Propulsion | PROCESS FOR PRODUCING BIOACTIVE COATINGS ON BONE PROSTHESES, AND PROSTHESES THUS OBTAINED |
EP0328041B1 (en) * | 1988-02-08 | 1994-09-07 | Mitsubishi Chemical Corporation | Ceramic implant and process for its production |
US5053212A (en) * | 1988-04-20 | 1991-10-01 | Norian Corporation | Intimate mixture of calcium and phosphate sources as precursor to hydroxyapatite |
-
1989
- 1989-02-06 US US07/307,326 patent/US4990163A/en not_active Expired - Fee Related
-
1990
- 1990-02-05 WO PCT/US1990/000663 patent/WO1990008520A1/en unknown
-
1992
- 1992-02-20 US US07/840,604 patent/US5171326A/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4308064A (en) * | 1978-10-19 | 1981-12-29 | Ngk Spark Plugs Co., Ltd. | Phosphate of calcium ceramics |
US4863475A (en) * | 1984-08-31 | 1989-09-05 | Zimmer, Inc. | Implant and method for production thereof |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5120340A (en) * | 1989-09-06 | 1992-06-09 | S.A. Fbfc International | Bioreactive material for a prosthesis or composite implants |
US5262166A (en) * | 1991-04-17 | 1993-11-16 | Lty Medical Inc | Resorbable bioactive phosphate containing cements |
EP0526682A1 (en) * | 1991-08-07 | 1993-02-10 | Oscobal Ag | Endoprosthesis with a metal wire mesh |
US5397359A (en) * | 1991-08-07 | 1995-03-14 | Oscobal Ag | Metal wire structure for endoprosthetics |
DE4128425A1 (en) * | 1991-08-27 | 1992-03-19 | Eska Medical Gmbh & Co | Medical implant prodn. with open-structured metallic surfaces - by lost-wax process where open-meshed surface element is reinforced with sprayed-osilicone@ or resin material |
WO1999062438A1 (en) * | 1998-06-03 | 1999-12-09 | Mathys Medizinaltechnik Ag | Plastic implant with metal netting |
WO2002049548A1 (en) * | 2000-12-21 | 2002-06-27 | Yuichi Mori | Indwelling instrument |
Also Published As
Publication number | Publication date |
---|---|
US5171326A (en) | 1992-12-15 |
US4990163A (en) | 1991-02-05 |
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