WO2000042991A1 - Inorganic shaped bodies and methods for their production and use - Google Patents
Inorganic shaped bodies and methods for their production and use Download PDFInfo
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- WO2000042991A1 WO2000042991A1 PCT/US2000/001629 US0001629W WO0042991A1 WO 2000042991 A1 WO2000042991 A1 WO 2000042991A1 US 0001629 W US0001629 W US 0001629W WO 0042991 A1 WO0042991 A1 WO 0042991A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
- A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
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- 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
- A61F2/28—Bones
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- 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
- A61F2/28—Bones
- A61F2/2875—Skull or cranium
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- 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
- A61F2/32—Joints for the hip
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
- C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B32/00—Artificial stone not provided for in other groups of this subclass
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- C—CHEMISTRY; METALLURGY
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- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
- C04B38/0022—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof obtained by a chemical conversion or reaction other than those relating to the setting or hardening of cement-like material or to the formation of a sol or a gel, e.g. by carbonising or pyrolysing preformed cellular materials based on polymers, organo-metallic or organo-silicon precursors
- C04B38/0025—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof obtained by a chemical conversion or reaction other than those relating to the setting or hardening of cement-like material or to the formation of a sol or a gel, e.g. by carbonising or pyrolysing preformed cellular materials based on polymers, organo-metallic or organo-silicon precursors starting from inorganic materials only, e.g. metal foam; Lanxide type products
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
- C04B38/009—Porous or hollow ceramic granular materials, e.g. microballoons
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- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
- A61B17/72—Intramedullary pins, nails or other devices
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
- A61B17/80—Cortical plates, i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
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- A—HUMAN NECESSITIES
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- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
- A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
- A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
- A61B17/84—Fasteners therefor or fasteners being internal fixation devices
- A61B17/86—Pins or screws or threaded wires; nuts therefor
- A61B17/866—Material or manufacture
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- 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
- A61F2002/30316—The prosthesis having different structural features at different locations within the same prosthesis; Connections between prosthetic parts; Special structural features of bone or joint prostheses not otherwise provided for
- A61F2002/30535—Special structural features of bone or joint prostheses not otherwise provided for
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- 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
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
- C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
- C04B2111/00793—Uses not provided for elsewhere in C04B2111/00 as filters or diaphragms
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
- C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
- C04B2111/0081—Uses not provided for elsewhere in C04B2111/00 as catalysts or catalyst carriers
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
- C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
- C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications
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- 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
- Y10S977/00—Nanotechnology
- Y10S977/902—Specified use of nanostructure
- Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
- Y10S977/906—Drug delivery
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- 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
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Definitions
- This invention relates to methods for the preparation of porous inorganic shaped bodies especially calcium phosphate-containing shaped bodies; to the bodies thus prepared; and to methods for use thereof.
- shaped bodies are provided which are at once, highly porous and uniform in composition. They can be produced in a wide range of geometric configurations through novel, low temperature techniques.
- the shaped bodies of the invention can be highly and uniformly porous while being self-supporting. They can be strengthened further using a variety of techniques, thereby forming porous composite structures.
- Such porous structures are useful as cell growth scaffolds, bone grafting materials, drug delivery vehicles, biological separation/purification media, catalysis and other supports and in a wide range of other uses.
- type-B carbonated hydroxyapatite (Ca5(PO4)3-x(CO3)x(OH) ] is the principal mineral phase found in the body, with variations in protein and organic content determining the ultimate composition, crystal size, morphology, and structure of the body portions formed therefrom.
- This invention overcomes those shortcomings and describes porous calcium phosphate and a wide variety of other inorganic materials which, in the case of calcium phosphates, closely resemble bone, and methods for the fabrication of such materials as shaped bodies for biological, chemical, industrial, and many other applications.
- the prior art also discloses certain methods for fabricating, inorganic shaped bodies using natural, organic objects. These fabrication methods, however, are not without drawbacks which include cracking upon drying the green body and/or upon firing. To alleviate these problems, the fabrication processes typically involve controlled temperature and pressure conditions to achieve the desired end product. In addition, prior fabrication methods may include the additional steps of extensive material preparation to achieve proper purity, particle size distribution and orientation, intermediate drying and radiation steps, and sintering at temperatures above the range desired for employment in the present invention. For example, U.S. Patent 5,298,205 issued to Hayes et. al.
- a further object of the invention is to provide methods for forming such materials with improved yields, lower processing temperatures, greater compositional flexibility, and better control of porosity.
- Yet another object provides materials with micro-, meso-, and macroporosity, as well as the ability to generate shaped porous solids having improved uniformity, biological activity, catalytic activity, and other properties.
- Another object is to provide porous materials which are useful in the repair and/or replacement of bone in orthopaedic and dental procedures.
- An additional object is to prepare a multiplicity of high purity, complex shaped objects, formed at temperatures below those commonly used in traditional firing methods.
- the present invention is directed to new inorganic bodies, especially controllably porous bodies, which can be formed into virtually any geometric shape.
- novel preparative methods of the invention utilize redox precipitation chemistry or aqueous solution chemistry, which is described in pending US Patent Application Serial No.
- the redox precipitation chemistry is utilized in conjunction with a sacrificial, porous cellular support, such as an organic foam or sponge, to produce a porous inorganic product which faithfully replicates both the bulk geometric form as well as the macro-, meso-, and microstructure of the precursor organic support.
- a sacrificial, porous cellular support such as an organic foam or sponge
- the aqueous solution because of its unique chemistry, has a high solids equivalent, yet can essentially be imbibed fully into and infiltrate thoroughly the microstructure of the sacrificial organic precursor material.
- inorganic shaped bodies have been fabricated possessing pore volumes of at least about 30%.
- pore volumes of over 50% have been attained and pore volumes in excess of 70%> or 80%> are more preferred.
- Materials having macro-, meso- and microporosity together with pore volumes of at least about 90% can be made as can those having pore volumes over 92% and even 94%. In some cases, pore volumes approaching 95% have been ascertained in products which, nevertheless, retain their structural integrity and pore structure.
- the phases produced by the methods of this invention [Redox Precipitation Reaction (RPR) and HYdrothermal PRocessing (HYPR)] initially are intermediate or precursor minerals, which can be easily converted to a myriad of pure and multiphasic minerals of previously known and, in some cases, heretofore undefined stoichiometry, generally via a thermal treatment under modest firing regimens compared to known and practiced conventional art.
- RPR Redox Precipitation Reaction
- HYPR HYdrothermal PRocessing
- a block of porous calcium phosphate material can be made to fit the dimensions of the missing or damaged bony tissue and implanted in place by itself or in conjunction with biocompatible bonding material compositions such as those disclosed in U. S. Patent No. 5,681,872 issued in the name of E. M. Erbe on Oct. 28, 1997 and incorporated herein by reference.
- the calcium phosphate material can also be used as a "sleeve" or form for other implants, as a containment vessel for the bone grafting material which is introduced into the sleeve for the repair, and in many other contexts.
- a major advantage of the restoration is that after polymerization, it has a significant, inherent strength, such that restoration of load-bearing bony sites can be achieved. While immobilization of the effected part will likely still be required, the present invention permits the restoration of many additional bony areas than has been achievable heretofore. Further, since the porous calcium phosphate scaffolding material of the present invention is biocompatible and, indeed, bioactive, osteogenesis can occur. This leads to bone infiltration and replacement of the calcium phosphate matrix with autologous bone tissue.
- the calcium phosphate scaffolding material of the present invention may also be made into shaped bodies for a variety of uses.
- orthopaedic appliances such as joints, rods, pins, or screws for orthopaedic surgery, plates, sheets, and a number of other shapes may be formed from the material in and of itself or used in conjunction with conventional appliances that are known in the art.
- Such hardened compositions can be bioactive and can be used, preferably in conjunction with hardenable compositions in accordance with the present invention in the form of gels, pastes, or fluids, in surgical techniques.
- a screw or pin can be inserted into a broken bone in the same way that metal screws and pins are currently inserted, using conventional bone cements or restoratives in accordance with the present invention or otherwise.
- the bioactivity of the present hardenable materials give rise to osteogenesis, with beneficial medical or surgical results.
- the methods of the invention are energy efficient, being performed at relatively low temperature; have high yields; and are amenable to careful control of product shape, macro- and microstructure, porosity, and chemical purity. Employment as bioactive ceramics is a principal, anticipated use for the materials of the invention, with improved properties being extant. Other uses of the porous minerals and processes for making the same are also within the spirit of the invention.
- the present invention also provides exceptionally fine, uniform powders of inorganic materials.
- Such powders have uniform morphology, uniform composition and narrow size distribution. They may be attained through the comminution of shaped bodies in accordance with the invention and have wide utility in chemistry, industry, medicine and otherwise.
- Figure 1 depicts an aggregated physical structure of an RPR generated, multiphasic ⁇ -tricalcium phosphate ( ⁇ -TCP) + type-B carbonated apatite (c-HAp) [ ⁇ - Ca3(PO4)2 + Ca5(PO 4 )3-x(CO3)x(OH)] prepared in accordance with one embodiment of this invention.
- the entire agglomerated particle is approximately 10 ⁇ m, and the individual crystallites are typically less than about 1 ⁇ m and relatively uniform in particle size and shape.
- Figure 3 illustrates a water purification disk that is comprised of the porous inorganic material of the present invention and is contained within an exterior housing for filtration or separation purposes.
- Figure 4 illustrates shaped bodies of porous inorganic material of the present invention used as a catalyst support within a hot gas reactor or diffusor.
- Figure 5 illustrates shaped bodies of porous calcium phosphate material of the present invention implanted at several sites within a human femur for cell seeding, drug delivery, protein adsorption, or growth factor scaffolding purposes.
- Figures 6 A and Figure 6B illustrate one embodiment of porous calcium phosphate scaffolding material of the present invention used as an accommodating sleeve in which a tooth is screwed, bonded, cemented, pinned, anchored, or otherwise attached in place.
- Figures 7 and 7 A illustrate another embodiment of the porous calcium phosphate scaffolding material of the present invention used as a cranio-maxillo facial, zygomatic reconstruction and mandibular implant.
- Figures 8 A and 8B illustrate one embodiment of the porous calcium phosphate scaffolding material of the present invention shaped into a block form and used as a tibial plateau reconstruction that is screwed, bonded, cemented, pinned, anchored, or otherwise attached in place.
- Figure 9 illustrates an embodiment of the porous calcium phosphate scaffolding material of the present invention shaped into a block or sleeve form and used for the repair or replacement of bulk defects in metaphyseal bone, oncology defects or screw augmentation.
- Figures 10A and 10B illustrate an embodiment of the porous calcium phosphate scaffolding material of the present invention shaped into a sleeve form and used for impaction grafting to accommodate an artificial implant said sleeve form being screwed, bonded, pinned or otherwise attached in place.
- Figure 11 is an X-ray diffraction (XRD) plot of a pulverized sample of porous calcium phosphate material fired at 500°C in accordance with one embodiment of this invention. The sample consists of a biphasic mixture of whitlockite Ca 3 (PO 4 ) 2 (PDF 09-0169) and hydroxyapatite Ca 5 (PO 4 ) 3 (OH) (PDF 09-0432).
- XRD X-ray dif
- Figure 12 is a 50X magnification scanning electron micrograph of a virgin cellulose sponge material used to prepare several of the embodiments of this invention.
- Figure 13 is a 100X magnification scanning electron micrograph of porous calcium phosphate material fired at 500°C in accordance with one embodiment of this invention.
- Figure 14 is an X-ray diffraction (XRD) plot of a pulverized sample of porous calcium phosphate material fired at 1100°C in accordance with one embodiment of this invention.
- the sample consists of whitlockite Ca 3 (PO 4 ) 2 (PDF 09-0169).
- Figure 15 is an X-ray diffraction (XRD) plot of a pulverized sample of porous calcium phosphate material fired at 1350°C in accordance with one embodiment of this invention.
- the sample consists of whitlockite Ca 3 (PO 4 ) 2 (PDF 09-0169).
- Figure 16 is an X-ray diffraction (XRD) plot of a pulverized sample of porous calcium phosphate material fired at 800°C in accordance with one embodiment of this invention.
- the sample consists of calcium pyrophosphate, Ca 2 P 2 O 7 (PDF 33-0297).
- Figure 17 is an X-ray diffraction (XRD) plot of a pulverized sample of porous zinc phosphate material fired at 500°C in accordance with one embodiment of this invention.
- the sample consists of zinc phosphate, Zn 3 (PO 4 ) 2 (PDF 30-1490).
- Figure 18 is an X-ray diffraction (XRD) plot of a pulverized sample of porous neodymium phosphate material fired at 500°C in accordance with one embodiment of this invention.
- the sample consists of neodymium phosphate, NdPO 4 (PDF 25-1065).
- Figure 19 is an X-ray diffraction (XRD) plot of a pulverized sample of porous aluminum phosphate material fired at 500°C in accordance with one embodiment of this invention.
- the sample consists of aluminum phosphate, AlPO 4 (PDF 11-0500).
- Figure 20 is a 23X magnification scanning electron micrograph depicting the macro- and meso-porosity of porous calcium phosphate material fired at 500°C and reinforced with gelatin in accordance with one embodiment of this invention.
- Figure 21 is a 25X magnification scanning electron micrograph of sheep trabecular bone for comparative purposes.
- Figure 22 is a 2000X magnification scanning electron micrograph of the air- dried gelatin treated inorganic sponge depicted in Figure 20 which exhibits meso- and microporosity in the calcium phosphate matrix.
- Figure 23 is an X-ray diffraction (XRD) plot of a pulverized sample of the ash remaining after firing at 500°C of the virgin cellulose sponge starting material used to prepare several of the embodiments of this invention.
- the ash sample consists of a biphasic mixture of magnesium oxide, MgO (major) (PDF 45-0946) and sodium chloride, NaCl (minor) (PDF 05-0628).
- Figure 24 is a 20X magnification scanning electron micrograph of a virgin cellulose sponge starting material, expanded from its compressed state, used to prepare several of the embodiments of this invention.
- Figure 25 is a 20X magnification scanning electron micrograph of porous calcium phosphate material fired at 800°C and reinforced with gelatin in accordance with one embodiment of this invention.
- Figure 26 depicts a calcium phosphate porous body, produced in accordance with one embodiment of this invention partially wicked with blood.
- Figure 27 shows a cylinder of calcium phosphate prepared in accordance with one embodiment of this invention, implanted into the metaphyseal bone of a canine.
- Figure 28 is an X-ray diffraction plot of a pulverized sample of a cation substituted hydroxyapatite material processed in accordance with the methods described in this invention.
- methods for preparing shapes comprising an intermediate precursor mineral of at least one metal cation and at least one oxoanion. These methods comprise preparing an aqueous solution of the metal cation and at least one oxidizing agent. The solution is augmented with at least one soluble precursor anion oxidizable by said oxidizing agent to give rise to the precipitant oxoanion.
- the oxidation-reduction reaction thus contemplated is conveniently initiated by heating the solution under conditions of temperature and pressure effective to give rise to said reaction.
- the oxidation- reduction reaction causes at least one gaseous product to evolve and the desired intermediate precursor mineral to precipitate from the solution.
- the intermediate precursor mineral thus prepared can either be used "as is” or can be treated in a number of ways. Thus, it may be heat treated in accordance with one or more paradigms to give rise to a preselected crystal structure or other preselected morphological structures therein.
- the oxidizing agent is nitrate ion and the gaseous product is a nitrogen oxide, generically depicted as NO x (g) . It is preferred that the precursor mineral provided by the present methods be substantially homogeneous. It is also preferred for many embodiments that the temperature reached by the oxidation-reduction reaction not exceed about 150 °C unless the reaction is run under hydrothermal conditions or in a pressure vessel.
- the intermediate precursor mineral provided by the present invention is a calcium phosphate. It is preferred that such mineral precursor comprise, in major proportion, a solid phase which cannot be identified singularly with any conventional crystalline form of calcium phosphate.
- the calcium phosphate mineral precursors of the present invention are substantially homogeneous and do not comprise a physical admixture of naturally occurring or conventional crystal phases.
- the low temperature processes of the invention lead to the homogeneous precipitation of high purity powders from highly concentrated solutions.
- Subsequent modest heat treatments convert the intermediate material to e.g. novel monophasic calcium phosphate minerals or novel biphasic ⁇ -tricalcium phosphate ( ⁇ -TCP) + type-B, carbonated apatite (c-HAp) [ ⁇ -Ca 3 (PO 4 ) 2 + Ca 5 (PO 4 ) 3- ⁇ (CO 3 ) x (OH)] particulates.
- calcium phosphate salts are provided through methods where at least one of the precursor anions is a phosphorus oxoanion, preferably introduced as hypophosphorous acid or a soluble alkali or alkaline-earth hypophosphite salt.
- the initial pH be maintained below about 3, and still more preferably below about 1.
- intermediate precursor minerals prepared in accordance with the present methods are, themselves, novel and not to be expected from prior methodologies. Thus, such precursor minerals can be, at once, non-stoichiometric and possessed of uniform morphology.
- the intermediate precursor minerals produced in accordance with the present methods be heated, or otherwise treated, to change their properties.
- such materials may be heated to temperatures as low as 300°C up to about 800°C to give rise to certain beneficial transformations.
- Such heating will remove extraneous materials from the mineral precursor, will alter its composition and morphology in some cases, and can confer upon the mineral a particular and preselected crystalline structure.
- Such heat treatment can be to temperatures which are considerably less than those used conventionally in accordance with prior methodologies to produce end product mineral phases.
- the heat treatments of the present invention do not, necessarily, give rise to the "common" crystalline morphologies of monetite, dicalcium or tricalcium phosphate, tetracalcium phosphate, etc., but, rather, they can lead to new and unobvious morphologies which have great utility in the practice of the present invention.
- the present invention is directed to the preparation, production and use of shaped bodies of inorganic materials. It will be appreciated that shaped bodies can be elaborated in a number of ways, which shaped bodies comprise an inorganic material. A preferred method for giving rise to the shaped bodies comprising minerals is through the use of subject matter disclosed in United State Serial Number 08/784,439 filed January 16,
- a blend of materials are formed which can react to give rise to the desired mineral, or precursor thereof, at relatively low temperatures and under relatively flexible reaction conditions.
- the reactive blends thus used include oxidizing agents and materials which can be oxidized by the oxidizing agent, especially those which can give rise to a phosphorus oxoanion. Many aspects of this chemistry are described hereinafter in the present specification.
- a principal object of the present invention is to permit such minerals to be formed in the form of shaped bodies.
- preferred compositions of this invention exhibit high degrees of porosity. It is also preferred that the porosity occur in a wide range of effective pore sizes.
- preferred embodiments of the invention have, at once, macroporosity, mesoporosity and microporosity. Macroporosity is characterized by pore diameters greater than about 100 ⁇ m. Mesoporosity is characterized by pore diameters between about 100 and 10 ⁇ m, while microporosity occurs when pores have diameters below about 10 ⁇ m. It is preferred that macro-, meso- and microporosity occur simultaneously in products of the invention. It is not necessary to quantify each type of porosity to a high degree.
- Pore Volume (l-f p ) 100%, where f p is fraction of theoretical density achieved. Pore volumes in excess of about 30% are easily achieved in accordance with this invention while materials having pore volumes in excess of 50 or 60% are also routinely attainable.
- materials of the invention have pore volumes of at least about 75%. More preferred are materials having pore volumes in excess of about 85%, with 90% being still more preferred. Pore volumes greater than about 92% are possible as are volumes greater than about 94%. In some cases, materials with pore volumes approaching 95% can be made in accordance with the invention. In preferred cases, such high pore volumes are attained while also attaining the presence of macro- meso- and microporosity as well as physical stability of the materials produced. It is believed to be a great advantage to be able to prepare inorganic shaped bodies having macro-, meso- and microporosity simultaneously with high pore volumes as described above.
- shaped bodies may be formed from minerals in this way which have remarkable macro- and microstructures.
- bodies can be prepared which are machinable, deformable, or otherwise modifiable into still other, desired states.
- the shaped bodies have sufficient inherent physical strength allowing that such manipulation can be employed.
- the shaped bodies can also be modified in a number of ways to increase or decrease their physical strength and other properties so as to lend those bodies to still further modes of employment.
- the present invention is extraordinarily broad in that shaped mineral bodies may be formed easily, inexpensively, under carefully controllable conditions, and with enormous flexibility.
- the microstructure of the materials that can be formed from the present invention can be controlled as well, such that they may be caused to emulate natural bone, to adopt a uniform microstructure, to be relatively dense, relatively porous, or, in short, to adopt a wide variety of different forms.
- the ability to control in a predictable and reproducible fashion the macrostructure, microstructure, and mineral identity of shaped bodies in accordance with the present invention under relatively benign conditions using inexpensive starting materials lends the technologies of the present invention to great medical, chemical, industrial, laboratory, and other uses.
- a reactive blend in accordance with the invention is caused to be imbibed into a material which is capable of absorbing it.
- the material have significant porosity, be capable of absorbing significant amounts of the reactive blend via capillary action, and that the same be substantially inert to reaction with the blend prior to its autologous oxidation-reduction reaction. It has been found to be convenient to employ sponge materials, especially cellulose sponges of a kind commonly found in household use for this purpose. Other sponges, including those which are available in compressed form such as Normandy sponges, are also preferred in certain embodiments.
- the substrate used to imbibe the reactive blend are not limited to organic materials and can include inorganic materials such as fiberglass.
- the sponges are caused to imbibe the reactive blend in accordance with the invention and are subsequently, preferably blotted to remove excess liquid.
- the reactive blend-laden sponge is then heated to whatever degree may be necessary to initiate the oxidation-reduction reaction of the reactive blend. Provision is generally made for the removal of by-product noxious gases, chiefly nitrogen oxide gases, from the site of the reaction.
- the reaction is exothermic, however the entire reacted body does not generally exceed a few hundred degrees centigrade. In any event, the reaction goes to completion, whereupon what is seen is an object in the shape of the original sponge which is now intimately comprised of the product of the oxidation reduction reaction.
- This material may either be the finished, desired mineral, or may be a precursor from which the desired product may be obtained by subsequent PRocessing.
- the cellulosic component of the sponge is pyrolyzed in a fugitive fashion, leaving behind only the mineral and in some cases, a small amount of ash.
- the resulting shaped body is in the form of the original sponge and is self-supporting. As such, it may be used without further transformation or it may be treated in one or more ways to change its chemical and or physical properties.
- the shaped body following the oxidation-reduction reaction can be heat treated at temperatures of from about 250°C to about 1400°C, preferably from 500°C to about 1000°C, and still more preferably from about 500°C to about 800 °C.
- a precursor mineral formed from the oxidation- reduction reaction may be transformed into the final mineral desired for ultimate use.
- temperatures in excess of 250° C may be employed in initiating the oxidation-reduction reaction and, indeed, any convenient temperature may be so utilized.
- methods of initiating the reaction where the effective temperature is difficult or impossible to determine, such a microwave heating may also be employed.
- the preferred procedures, however, are to employ reaction conditions to initiate, and propagate if necessary, the reaction are below the temperature wherein melting of the products occur. This is in distinction with conventional glass and ceramic processing methods.
- the shaped bodies thus formed may be used in a number of ways directly or may be further modified.
- either the as-formed product of the oxidation-reduction reaction may be modified, or a resulting, transformed mineral structure may be modified, or both.
- Various natural and synthetic polymers, pre-polymers, organic materials, metals and other adjuvants may be added to the inorganic structures thus formed.
- wax, glycerin, gelatin, pre-polymeric materials such as precursors to various nylons, acrylics, epoxies, polyalkylenes, and the like, may be caused to permeate all or part of the shaped bodies formed in accordance with the present invention. These may be used to modify the physical and chemical nature of such bodies.
- the shaped bodies prepared in accordance with the present invention may be formed in a very large variety of shapes and structures. It is very easy to form cellulose sponge material into differing shapes such as rings, rods, screw-like structures, and the like. These shapes, when caused to imbibe a reactive blend, will give rise to products which emulate the original shapes. It is also convenient to prepare blocks, disks, cones, frustrums or other gross shapes in accordance with the present invention which shapes can be machined, cut, or otherwise manipulated into a final desired configuration. Once this has been done, the resulting products may be used as is or may be modified through the addition of gelatin, wax, polymers, and the like, and used in a host of applications.
- the resulting product replicates the shape and morphology of the sponge.
- Modifications in the shape of the sponge, and in its microstructure can give rise to modifications in at least the intermediate structure and gross structures of the resulting products.
- the microstructure of shaped bodies prepared in accordance with the present invention frequently include complex and highly desirable features.
- microstructure of materials produced in accordance with the present invention can show significant microporosity.
- the microstructure can be custom-tailored based upon the absorbent material selected as the fugitive support.
- One particular embodiment which used a kitchen sponge as the absorbent material, exhibited a macro- and microstructure similar to the appearance of ovine trabecular bone. This highly surprising, yet highly desirable result gives rise to obvious benefits in terms of the replication of bony structures and to the use of the present invention in conjunction with the restoration of bony tissues in animals and especially in humans.
- the present invention finds utility in a wide variety of applications.
- the shaped bodies may be used in medicine, for example for the restoration of bony defects and the like.
- the materials may also be used for the delivery of medicaments internal to the body.
- the porosity of a material formed in accordance with the invention may be all or partially filled with another material which either comprises or carries a medicament such as a growth hormone, antibiotic, cell signaling material, or the like.
- the larger porous spaces within some of the products of the present invention may be used for the culturing of cells within the human body.
- the larger spaces are amenable to the growth of cells and can be permeated readily by bodily fluids such as certain blood components.
- growing cells may be implanted in an animal through the aegis of implants in accordance with the present invention. These implants may give rise to important biochemical or therapeutic or other uses.
- Shaped bodies formed from the present invention may be formed to resemble saddles, rings, disks, honeycombs, spheres, tubes, matrixes, and, in short, a huge array of shapes, which shapes may be used for engineering purposes.
- shapes may be made from minerals which incorporate catalytic components such as rare earths, precious and base metals, palladium, platinum, Raney nickel and the like for catalytic use.
- These shapes may also be used for column packing for distillation and other purposes.
- the shapes may be capable of serving a plurality of uses at once, such as being a substrate for refluxing while acting as a catalyst at the same time.
- the bodies of the present invention will also be suitable for chromatography and other separation and purification techniques. Thus, they may serve as substrates for mobile phases in the same way that a capillary suspends a gelatinous material for capillary gel electrophoresis.
- the present invention also provides filtration media.
- the porous structures of the present invention may serve as filters. Due to the ability to formulate these shaped bodies in a wide variety of carefully controlled ways, some unique structures may be attained.
- an anisotropic membrane as known to persons of ordinary skill in the art, and frequently referred to as a "Michaels" membrane may be used for the imbibation of reactive blend in accordance with the invention. Following redox reaction and removal of the membranous material as a fugitive phase, the resulting inorganic structure is also anisotropic. It is thus possible to utilize materials and shaped bodies in accordance with the present invention as an anisotropic but inorganic filtration media.
- the shaped bodies may be coated, such as with a polymer.
- a polymer may be any of the film forming polymers or otherwise and may be used for purposes of activation, conductivity, passivation, protection, or other chemical and physical modification.
- the bodies may also be contacted with a "keying agent" such as a silane, or otherwise to enable the grafting of different materials onto the surface of the polymer.
- the shaped bodies of the invention may also be used for the growth of oligomers on their surfaces. This can be done in a manner analogous to a Merrifield synthesis, an oligonucleotide synthesis or otherwise. Such shaped bodies may find use in conjunction with automated syntheses of such oligomers and may be used to deliver such oligomers to the body of an animal, to an assay, to a synthetic reaction vessel, or otherwise. Since the mineral composition of the shaped bodies of this invention may be varied so • widely, it is quite suitable to the elaboration of oligomers as suggested here and above.
- Grafting of other inorganic materials, silanes, especially silicones and similar materials, is a particular feature of the present invention.
- the grafting reactions, keying reactions, oligomer extension reactions and the like are all known to persons skilled in the art and will not be repeated here. Suffice it to say that all such reactions are included within the scope of the present invention.
- the shaped bodies of the invention may also be coated through surface layer deposition techniques such as plasma coating, electroless plating, chemical vapor deposition (CVD), physical vapor deposition (PVD), or other methods.
- surface layer deposition techniques such as plasma coating, electroless plating, chemical vapor deposition (CVD), physical vapor deposition (PVD), or other methods.
- CVD chemical vapor deposition
- PVD physical vapor deposition
- the surface structure of the shaped bodies may be modified in carefully controlled ways for catalytic, electronic, and other purposes.
- the chemistry and physics of chemical vapor deposition and other coating techniques are known to persons of ordinary skill in the art whose knowledge is hereby assumed.
- the shaped bodies produced hereby may be comminuted to yield highly useful and unique powder materials finding wide utility.
- shaped bodies may be crushed, milled, etc. and preferably classified or measured, such as with a light scattering instrument, to give rise to fine powders.
- Such powders are very small and highly uniform, both in size, shape and chemical composition.
- Particles may be prepared having particle size number means less than about 0.1 ⁇ m or 100 nanometers. Smaller mean sized may also be attained.
- this invention provides highly uniform inorganic materials in powder form having particle sizes, measured by light scattering techniques such that the number mean size is between about 0.1 and 5.0 ⁇ m. Particle sizes between about 0.5 and 2.0 ⁇ m may also be attained.
- the morphology of the particles is highly uniform, deriving, it is thought, from the microporosity of the shaped bodies from which they arise.
- the particles are also highly uniform chemically. Since they arise from a chemical reaction from a fully homogenous solution, such uniformity is much greater than is usually found in glass or. ceramic melts.
- Particle size number means are easily determined with a Horiba LA-910 instrument. Number means refers to the average or mean number of particles having the size or size range in question.
- molded golf ball may easily be made such as via the processes of Bartsch, including a calcium phosphate powder of this invention admixed with a crosslinked acrylic polymer system.
- shaping techniques are employed on the formed, shaped bodies of the present invention.
- such bodies may be machined, pressed, stamped, drilled, lathed, or otherwise mechanically treated to adopt a particular shape both externally and internally.
- preforms may be formed in accordance with the invention from which shapes may be cut or formed.
- an orthopaedic sleeve for a bone screw may be machined from a block of calcium phosphate made hereby, and the same tapped for screw threads or the like. Carefully controllable sculpting is also possible such that precisely-machined shapes may be made for bioimplantation and other uses.
- shaped bodies may be formed through casting, extrusion, foaming, doctor blading, spin molding, spray forming, and a host of other techniques. It is possible to extrude hollow shapes in the way that certain forms of hollow pasta are extruded. Indeed, machinery useful for the preparation of certain food stuffs may also find beneficial use in conjunction with certain embodiments of the present invention. To this end, food extrusion materials such as that used for the extrusion of "cheese puffs" or puffed cereals may be used. These combine controllable temperature and pressure conditions with an extrusion apparatus. Through careful control of the physical conditions of the machinery, essentially finished, oxidation-reduction product may be extruded and used as-is or in subsequently modified form.
- a film of reactive blend may be doctored onto a surface, such as stainless steel or glass, and the film caused to undergo an oxidation-reduction reaction.
- the resulting material can resemble a potato chip in overall structure with variable porosity and other physical properties.
- the present invention is also amenable to the use of other organic material capable of imbibing reactive blend.
- other organic material capable of imbibing reactive blend.
- the resulting oxidation reduction product assumes the form of the gauze.
- a flannel material will give rise to a relatively thick pad of inorganic material from which the organic residue may be removed through the application of heat.
- Cotton or wool may be employed as may be a host of other organic materials. It is also possible to employ inorganic materials and even metals in accordance with the present invention.
- inclusion of conductive mesh, wires, or conductive polymers in materials which form the substrate for the oxidation reduction of the reactive blend can give rise to conductive, mineral-based products.
- the minerals may be formed or modified to include a wide variety of different elements, the same may be caused to be catalytic.
- the combination of a porous, impermeable, catalytic material with conductivity makes the present invention highly amenable to use in fuel cells, catalytic converters, chemical reaction apparatus and the like.
- the ceramics of the invention may be piezoelectric, may be transparent to microwave radiation and, hence, useful in radomes and the like. They may be ion responsive and, therefore, useful as electrochemical sensors, and in many other ways.
- the materials of the invention may be formulated so as to act as pharmaceutical excipients, especially when comminuted, as gas scrubber media, for pharmaceutical drug delivery, in biotechno logical fermentation apparatus, in laboratory apparatus, and in a host of other applications.
- transition metal phosphates including those of scandium, titanium, chromium, manganese, iron, cobalt, nickel, copper, and zinc may be elaborated into pigments, phosphors, catalysts, electromagnetic couplers, microwave couplers, inductive elements, zeolites, glasses, and nuclear waste containment systems and coatings as well as many others.
- Rare earth phosphates can form intercalation complexes, catalysts, glasses, ceramics, radiopharmaceuticals, pigments and phosphors, medical imaging agents, nuclear waste solidification media, electro-optic components, electronic ceramics, surface modification materials and many others.
- Aluminium and zirconium phosphates can give rise to surface protection coatings, abrasive articles, polishing agents, cements, filtration products and otherwise.
- Alkali and alkaline earth metal phosphates are particularly amenable to low temperature glasses, ceramics, biomaterials, cements, glass-metal sealing materials, glass- ceramic materials including porcelains, dental glasses, electro-optical glasses, laser glasses, specific refractive index glasses, optical filters and the like.
- the minerals formed hereby and the shaped bodies comprising them are useful in a wide variety of industrial, medical, and other fields.
- calcium phosphate minerals produced in accordance with preferred embodiments of the present invention may be used in dental and orthopaedic surgery for the restoration of bone, tooth material and the like.
- the present minerals may also be used as precursors in chemical and ceramic processing, and in a number of industrial methodologies, such as crystal growth, ceramic processing, glass making, catalysis, bioseparations, pharmaceutical excipients, gem synthesis, and a host of other uses.
- Uniform microstructures of unique compositions of minerals produced in accordance with the present invention confer upon such minerals wide utility and great "value added.” Indeed, submicron microstructure can be employed by products of the invention with the benefits which accompany such microstructures.
- Improved precursors provided by this invention yield lower formation temperatures, accelerated phase transition kinetics, greater compositional control, homogeneity, and flexibility when used in chemical and ceramic processes. Additionally, these chemically-derived, ceramic precursors have fine crystal size and uniform morphology with subsequent potential for very closely resembling or mimicking natural tissue structures found in the body.
- “acidic” calcium phosphate crystalline phases include dicalcium phosphate dihydrate (brushite -DCPD, CaHPO 4 «H 2 O), dicalcium phosphate anhydrous (monetite-DCPA, CaHPO 4 ), monocalcium phosphate monohydrate (MCPM, Ca(H 2 PO 4 ) 2 -H 2 O), and monocalcium phosphate anhydrous (MCPA, Ca(H 2 PO 4 ) 2 ). These calcium phosphate compounds are of critical importance in the area of bone cements and bone grafting materials.
- these phases are obtained via thermal or hydrothermal conversion of (a) solution-derived precursor calcium phosphate materials, (b) physical blends of calcium salts, or (c) natural coral.
- Thermal transformation of synthetic calcium phosphate precursor compounds to TCP or TTCP is achieved via traditional ceramic processing regimens at high temperature, greater than about 800 °C.
- the "basic" calcium phosphate materials used in the art (Ca/P > 1.5) have generally all been subjected to a high temperature treatment, often for extensive periods of time.
- For other preparations of "basic" calcium phosphate materials see also H. Monma, S. Ueno, and T.
- Kanazawa "Properties of hydroxyapatite prepared by the hydrolysis of tricalcium phosphate," J. Chem. Tech. Biotechnol. 31: 15 (1981); H. Chaair, J.C. Heughebaert, and M. Heughebaert, "Precipitation of stoichiometric apatitic tricalcium phosphate prepared by a continuous process," J. Mater. Chem. 5(6): 895 (1995); R. Famery, N. Richard, and P. Boch, "Preparation of alpha- and beta-tricalcium phosphate ceramics, with and without magnesium addition," Ceram. Int. 20: 327 (1994); Y. Fukase, E.D. Eanes, S. Takagi, L.C. Chow, and W.E. Brown, “Setting reactions and compressive strengths of calcium phosphate cements," J. Dent. Res. 69(12): 1852 (1990).
- the present invention represents a significant departure from prior methods for synthesizing metal phosphate minerals and porous shaped bodies of these materials, particularly calcium phosphate powders and materials, in that the materials are formed from homogeneous solution using a novel Redox Precipitation Reaction (RPR). They can be subsequently converted to TCP , HAp and/or combinations thereof at modest temperatures and short firing schedules. Furthermore, precipitation from homogeneous solution (PFHS) in accordance with this invention, has been found to be a means of producing particulates of uniform size and composition in a form heretofore not observed in the prior art.
- RPR Redox Precipitation Reaction
- hypophosphite [H 2 PO 2 " ] anion as a precursor to phosphate ion generation has been found to be preferred since it circumvents many of the solubility constraints imposed by conventional calcium phosphate precipitation chemistry and, furthermore, it allows for uniform precipitation at high solids levels. For example, reactions can be performed in accordance with the invention giving rise to product slurries having in excess of 30% solids. Nitrate anion is the preferred oxidant, although other oxidizing agents are also useful.
- Nitrate anion under strongly acidic conditions as the oxidant for the hypophosphite to phosphate reaction is beneficial from several viewpoints.
- Nitrate is readily available and is an inexpensive oxidant. It passivates stainless steel (type
- NO x oxidation byproducts
- any residual nitrate will be fugitive, as NO x under the thermal conversion schedule to which the materials are usually subjected, thus leading to exceedingly pure final materials.
- RPR reduction-oxidation precipitation reactions
- the driving force for the RPR is the concurrent reduction and oxidation of anionic species derived from solution precursors.
- Advantages of the starting solutions can be realized by the high initial concentrations of ionic species, especially calcium and phosphorus species. It has been found that the use of reduced phosphorus compounds leads to solution stability at ionic concentrations considerably greater than if fully oxidized [PO 4 ] 3 species were used.
- Conventional processing art uses fully oxidized phosphorus oxoanion compounds and is, consequently, hindered by pH, solubility, and reaction temperature constraints imposed by the phosphate anion.
- Typical reducible species are preferably nitric acid, nitrate salts (e.g. Ca(NO 3 ) 2 4H 2 O), or any other reducible nitrate compound, which is highly soluble in water.
- Other reducible species include nitrous acid (HNO 2 ) or nitrite (NO 2 ) salts.
- hypophosphorous acid or hypophosphite salts [e.g. Ca(H 2 PO 2 ) 2 ] which are highly soluble in water.
- Other oxidizable species which find utility include acids or salts of phosphites (HPO 3 2 ⁇ ), pyrophosphites (H 2 P 2 O 5 2" ), thiosulfate (S 2 O 3 2" ) , tetrathionate (S 4 O 6 2" ), dithionite (S 2 O 4 2' ) trithionate (S 3 O 6 2 ) , sulfite (SO 3 2" ), and dithionate (S 2 O 6 2” )-
- HPO 3 2 ⁇ phosphites
- pyrophosphites H 2 P 2 O 5 2"
- thiosulfate S 2 O 3 2"
- S 4 O 6 2 tetrathionate
- dithionite S 2 O 4 2'
- SO 3 2 sulfite
- the cation introduced into the reaction mixture with either or both of the oxidizing or reducing agents are preferably oxidatively stable (i.e. in their highest oxidation state). However, in certain preparations, or to effect certain reactions, the cations may be introduced in a partially reduced oxidation state. Under these circumstances, adjustment in the amount of the oxidant will be necessary in order to compensate for the electrons liberated during the oxidation of the cations during RPR.
- thermodynamics will determine whether a particular reaction is possible, kinetic effects may be very much more important in explaining the absence or presence of particular calcium phosphate phases during precipitation reactions.
- soluble calcium ion is maintained at concentrations of several molar in the presence of soluble hypophosphite anion which is, itself, also at high molar concentrations.
- the solution is also at a very low pH due to the presence of nitric and hypophosphorous acids.
- such solutions of calcium and hypophosphite ions can be stable indefinitely with respect to precipitation, at room temperature or below.
- the first oxoacid anion undergoes oxidation (increase in chemical oxidation state) to generate the precipitant anionic species along with concurrent reduction (decrease in chemical oxidation state) of the nonmetallic element of a second, dissimilar oxoacid anion, all oxoacid anions initially being present in solution with one or more metal cations known to form insoluble salts with the precipitant anion.
- the metal cations are, preferably, oxidatively stable, but may undergo oxidation state changes themselves under certain conditions.
- RPR is induced preferably by heating a homogeneous solution, so as to promote the onset and continuation of an exothermic redox reaction.
- This exothermic reaction results in the generation of gases, usually various nitrogen oxide gases such as
- reaction yield is high as is the purity of the reaction products.
- the use of alternate heating methods to initiate and complete the RPR reaction may offer utility in the formation of scaffold structures.
- One such power source is microwave energy, as found in conventional 600-1400 W home microwave ovens.
- the benefit of the use of microwaves is the uniformity of the heating throughout the entire reaction mass and volume as opposed to the external-to-internal, thermal gradient created from traditional conduction/convection/radiant heating means.
- the rapid, internal, uniform heating condition created by the use of microwave energy provides for rapid redox reaction initiation and drying.
- the excess RPR liquid is expelled to the outer surface of the cellulose body and flashes off to form an easily removed deposit on the surface.
- the rapid rate of heating and complete removal of the fugitive substructure alters the particulate structure resulting in greater integral strength.
- the speed of heating and initiation of the RPR reaction may also minimize crystal grain growth.
- the nitrate / hypophosphite redox system involves a hypophosphite oxidation to phosphate (P +1 to P +5 , a 4e " oxidation) as depicted in the following equations (E 0 /V from N.N. Greenwood and A. Earnshaw, "Oxoacids of phosphorus and their salts," in Chemistry of the Elements, pp 586-595 (1984), Pergamon Press):
- H 3 PO 3 + 2H + + 2e " H 3 PO 2 + H 2 O -0.499
- Chemical reactions are conveniently expressed as the sum of two (or more) electrochemical half-reactions in which electrons are transferred from one chemical species to another. According to electrochemical convention, the overall reaction is represented as an equilibrium in which the forward reaction is stated as a reduction (addition of electrons), i.e.:
- Oxidized species + ne ⁇ Reduced species
- the reaction is spontaneous from left to right if E 0 (the reduction potential) is greater than 0, and spontaneous in the reverse direction if E 0 is less than 0.
- nitrate is a strong oxidant capable of oxidizing hypophosphite (P +1 ) to phosphite (P +3 ) or to phosphate (P +5 ) regardless of the reduction reaction pathway, i.e., whether the reduction process occurs according to Equation 4, 5, or 6.
- Eq.3 oxidation reaction
- Eq.6 reduction reaction
- the invention generally allows for the in situ homogeneous production of simple or complex oxoacid anions in aqueous solution in which one or more nonmetallic elements such as Group 5B and 6B
- chalcogenides and 7B (halides) comprising the first oxoacid anion undergoes oxidation to generate the precipitant anionic species along with concurrent reduction of the nonmetallic element of a second, dissimilar oxoacid anion.
- the remodeling behavior of a calcium phosphate bioceramic to bone is dictated by the energetics of the surface of the ceramic and the resultant interactions with osteoclastic cells on approach to the interface.
- Unique microstructures can yield accelerated reactivity and, ultimately, faster remodeling in vivo.
- the compositional flexibility in the fine particles of this invention offers adjustable reactivity in vivo.
- the crystallite size and surface properties of the resultant embodiments of this invention are more similar to the scale expected and familiar to the cells found in the body. Mixtures of powders derived from the processes of this invention have tremendous utility as calcium phosphate cements (CPCs).
- An aqueous solution can be prepared in accordance with the present invention and can be imbibed into a sacrificial organic substrate of desired shape and porosity, such as a cellulose sponge.
- the solution-soaked substrate is subjected to controlled temperature conditions to initiate the redox precipitation reaction.
- a subsequent heating step is employed to combust any remaining organic material and/or promote phase changes.
- the resultant product is a porous, inorganic material which mimics the shape, porosity and other aspects of the morphology of the organic substrate.
- FIG. 3 depicts a discoidal filter scaffold
- discoidal filter scaffold 16 which is prepared in accordance with the present invention, and enclosed within an exterior filter housing 18 for filtration or bioseparation applications.
- discoidal filter scaffold 16 can be a biologically active, impregnated porous scaffold.
- Arrow 20 represents the inlet flow stream.
- Arrow 22 represents the process outlet stream after passing through discoidal filter scaffold 16.
- Figure 4 illustrates a block of the porous inorganic material that is used as a catalyst support within a two stage, three way hot gas reactor or diffusor.
- Items 30 and 32 illustrate blocks of the porous material used as catalytically impregnated scaffolds. Items 30 and 32 may be composed of the same or different material. Both 30 and 32, however, are prepared in accordance with an embodiment of the present invention.
- Item 34 depicts the first stage catalyst housing, which may be comprised of a ferrous-containing material, and encloses item 30.
- Item 36 depicts the second stage catalyst housing, which may be comprised of a ferrous-containing material, and encloses item 32.
- Item 38 represents the connector pipe, which is comprised of the same material as the housings 34 and 36, and connects both 34 and 36.
- Arrow 40 represents the raw gas inlet stream prior to passing through both blocks of catalytically impregnated scaffold (items 30 and 32).
- Arrow 42 lastly, represents the processed exhaust gas stream.
- the inorganic porous material is a calcium phosphate scaffolding material that may be employed for a variety of uses.
- Figure 5 illustrates a block of the calcium phosphate scaffolding material 55 that may be inserted into a human femur and used for cell seeding, drug delivery, protein adsorption, growth factor introduction or other biomedical applications.
- Femoral bone 51 is comprised of metaphysis 52, Haversian canal 53, diaphysis 54 and cortical bone 56.
- the calcium phosphate scaffolding material 55 is inserted into an excavation of the femoral bone as shown and ties into the Haversian canal allowing cell seeding, drug delivery, or other applications. Scaffolding material 55 can be used in the same manner in a variety of human or mammalian bones.
- Figure 6 A shows the calcium phosphate material of the present invention formed into the shape of a calcium phosphate sleeve 60.
- Item 62 depicts the excavated cavity which can be formed via machining or other means.
- Item 64 presents a plurality of threads which can be coated with bioactive bone cement.
- Figure 6B shows the calcium phosphate sleeve 60 inserted into the jaw bone 66 and gum 67.
- the calcium phosphate sleeve 60 may be fixed in place via pins, bone cement, or other mechanical means of adhesion.
- An artificial tooth or dental implant 68 can then be screwed into sleeve 60 by engaging threads 64.
- Figure 7A shows the porous, calcium phosphate scaffolding material 70, prepared in accordance with an embodiment of the present invention, which is machined or molded to patient specific dimensions.
- Figure 7B depicts the use of the material 70 that is formed into the shape of craniomaxiUofacial implant 76, a zygomatic reconstruction 72, or a mandibular implant 74.
- Figure 8 A depicts a plug of the porous, calcium phosphate scaffolding material 80.
- Figure 8B illustrates plug 80 which is inserted into an excavation site 83 within a human knee, below the femur 81 and above the tibia 82, for use in a tibial plateau reconstruction.
- Plug 80 is held in place or stabilized via a bone cement layer 84.
- Figure 9 shows the calcium phosphate scaffolding material within a human femur that is used as a block 92 for bulk restoration or repair of bulk defects in metaphyseal bone or oncology defects, or as a sleeve 94 for an orthopaedic screw, rod or pin 98 augmentation.
- Item 99 depicts an orthopaedic plate anchored by the orthopaedic device item 98. Bone cement layer 96 surrounds and supports sleeve 94 in place.
- Figures 10A and 10B depict the use of the calcium phosphate scaffolding material as a receptacle sleeve 100 that is inserted into the body to facilitate a bipolar hip replacement. Cavity 102 is machined to accommodate the insertion of a metallic ball joint implant or prosthesis 103. An orthopaedic surgeon drills a cavity or furrow into the bone 101 to receive sleeve 100. Sleeve 100 is then affixed to the surrounding bone via a bioactive or biocompatible bone cement layer 104 or other means.
- a femoral head articulation surface 106 is cemented to a bone cement layer 104 that resides within a prepared cavity with material of the present invention, 100.
- a high molecular weight polyethylene cup, 105 is used to facilitate articulation with the head of the prosthesis 103.
- the metallic ball joint implant or prosthesis 103 is thus inserted into a high molecular weight polyethylene cup 105 to facilitate joint movement.
- Orthopaedic appliances such as joints, rods, pins, sleeves or screws for orthopaedic surgery, plates, sheets, and a number of other shapes may be formed from the calcium phosphate scaffolding material in and of itself or used in conjunction with conventional appliances that are known in the art.
- Such porous inorganic bodies can be bioactive and can be used, preferably, in conjunction with biocompatible gels, pastes, cements or fluids and surgical techniques that are known in the art.
- a screw or pin can be inserted into a broken bone in the same way that metal screws and pins are currently inserted, using conventional bone cements or restoratives in accordance with the present invention or otherwise.
- the bioactivity of the calcium phosphate scaffolding material will give rise to osteogenesis with beneficial medical or surgical results.
- calcium phosphate particles and/or shaped bodies prepared in accordance with this invention can be used in any of the orthopaedic or dental procedures known for the use of calcium phosphate; the procedures of bone filling defect repair, oncological defect filling, craniomaxiUofacial void filling and reconstruction, dental extraction site filling, and potential drug delivery applications.
- the scaffold structures of this invention can be imbibed with blood, cells (e.g. fibroblasts, mesenchymal, stromal, marrow and stem cells), protein rich plasma other biological fluids and any combination of the above.
- cells e.g. fibroblasts, mesenchymal, stromal, marrow and stem cells
- protein rich plasma other biological fluids e.g. ovine and canine blood (37 °C) showing the ability of the scaffold to maintain its integrity while absorbing the blood into its pores.
- ovine and canine blood 37 °C
- This capability has utility in cell-seeding, drug delivery, and delivery of biologic molecules as well as in the application of bone tissue engineering, orthopaedics, and carriers of pharmaceuticals.
- the scaffold structures can be imbibed with any bioabsorbable polymer or film-forming agent such as polycaprolactones (PCL), polyglycolic acid (PGA), poly-L-Lactic acid (PL-LA), polysulfones, polyolefins, polyvinyl alcohol (PVA), polyalkenoics, polyacrylic acids (PAA), polyesters and the like.
- PCL polycaprolactones
- PGA polyglycolic acid
- PL-LA poly-L-Lactic acid
- PVA polysulfones
- polyolefins polyvinyl alcohol
- PAA polyalkenoics
- polyesters polyesters and the like.
- Transition metal phosphates (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) and shaped, porous articles thereof have numerous potential uses as pigments, phosphors, catalysts, electromagnetic couplers, microwave couplers, inductive elements, zeolites, glasses, nuclear waste containment systems, radomes and coatings. Addition of rare-earths phosphates can lead to uses as intercalation compounds, catalysts, catalyst support material, glasses and ceramics, radiopharmaceuticals, pigments and phosphors, medical imaging agents, nuclear waste solidification, electro-optics, electronic ceramics, and surface modifications.
- Aluminum and zirconium phosphates and shaped, porous articles thereof are ideal candidates for surface protective coatings, abrasive particles, polishing agents, cements, and filtration products in either granular form or as coatings.
- the alkali Na, K,
- Rb, Cs) and alkaline-earth (Be, Mg, Ca, Sr, Ba) phosphates and shaped, porous articles thereof would generate ideal low temperature glasses, ceramics, biomaterials, cements, glass to metal seals, and other numerous glass-ceramic materials, such as porcelains, dental glasses, electro-optic glasses, laser glasses, specific refractive index glasses and optical filters.
- Example 1 Low Temperature Calcium Phosphate Powders An aqueous solution of 8.51 g 50 wt% hypophosphorous acid, H 3 PO 2
- the molar ratio of Ca/phosphate in this mixture was 3/2 and the equivalent solids level [as Ca 3 (PO 4 ) 2 ] was 25.4 w ⁇ %.
- Endothermic dissolution of the calcium nitrate tetrahydrate proceeded under ambient temperature conditions, eventually forming a homogeneous solution. Warming of this solution above 25 °C initiated a reaction in which the solution vigorously bubbled while evolving red-brown acrid fumes characteristic of NO x (g) .
- the sample turned into a white, pasty mass which foamed and pulsed with periodic expulsion of NO x (g) . After approximately two minutes, the reaction was essentially complete, leaving a white, pasty mass which was warm to the touch.
- the solid (A) was stored in a polyethylene vial.
- 700 °C was comprised of whitlockite and hydroxyapatite.
- Example 1 was repeated using five times the indicated weights of reagents.
- the reactants were contained in a 5-1/2" diameter Pyrex crystallizing dish on a hotplate with no agitation. Warming of the homogeneous reactant solution above 25 °C initiated an exothermic reaction which evolved red-brown acrid fumes characteristic of NO x (g) . Within a few seconds following onset of the reaction, the sample turned into a white, pasty mass which continued to expel NO x (g) for several minutes. After approximately five minutes, the reaction was essentially complete leaving a damp solid mass which was hot to the touch. This solid was cooled to room temperature under ambient conditions for approximately 20 minutes and divided into two portions prior to heat treatment.
- Example 3 Low Temperature Calcium Phosphate Powders An aqueous solution of 8.51 g 50 wt% H 3 PO 2 was combined with 8.00 g of
- Example 1 >25 °C on a hotplate initiated a reaction which proceeded as described in Example 1. After approximately three minutes, the reaction was essentially complete leaving a moist, white, crumbly solid which was hot to the touch and which smelled of acetic acid. After cooling to room temperature, the solid was stored in a polyethylene vial. Heat treatment and X-ray diffraction analysis of this solid were conducted as described in Example 1. Following heat treatment in air at 500 °C for either 0.5 or 1 hour, XRD indicated the solid to be composed of whitlockite as the primary phase along with hydroxylapatite as the secondary phase. XRD results indicate that the relative ratio of the two calcium phosphate phases was dependent on the duration of the heat treatment and the presence of the acetate anion, but no attempts were made to quantify the dependence.
- Example 1 shows the difference in the amount of HAp- Ca 5 (PO ) 3 _ x (CO 3 ) x (OH) phase present for each minor phase.
- the samples in Example 1 exhibited no acetate whereas the samples in Example 3 showed acetate present. This is indicative of the counteranion effect on crystal formation.
- FTIR Fourier Transform Infrared
- Example 4 Colloidal SiO 2 added to calcium phosphate mixtures via RPR.
- the colloidal SiO 2 was not flocculated despite the high acidity and ionic strength in the sample. Warming of the sample on a hotplate to >25 °C initiated a reaction as described in Example 1. The resultant white, pasty solid was stored in a polyethylene vial.
- Example 1 was repeated with the addition of lO.OOg dicalcium phosphate dihydrate, DCPD, CaHPO42H 2 O (Aldrich Chemical Co., Inc. #30,765-3, CAS #7789-77- 7) to the homogeneous solution following endothermic dissolution of the calcium nitrate salt.
- the DCPD was present both as suspended solids and as precipitated material (no agitation used).
- Warming of the sample to >25 °C initiated an exothermic reaction as described in Example 1, resulting in the formation of a white, pasty solid.
- Heat treatment and X-ray diffraction of this solid were conducted as described in Example 1. Following heat treatment in air at 500 °C for 1 hour, XRD indicated the solid to be composed of whitlockite as the primary phase along with calcium pyrophosphate (Ca 2 P 2 O 7 ) as the secondary phase.
- reaction continued for approximately 10 minutes while the sample remained a clear, colorless solution, abated somewhat for a period of five minutes, then vigorously resumed finally resulting in the formation of a mass of moist white solid, some of which was very adherent to the walls of the Pyrex beaker used as a reaction vessel.
- the hot solid was allowed to cool to room temperature and was stored in a polyethylene vial.
- Example 7 Low Temperature Iron Phosphate Powders An aqueous solution of 17.50 g 50 wt% H 3 PO 2 was combined with 15.00 g distilled water to form a clear, colorless solution contained in a 250 ml Pyrex beaker on a hotplate/stirrer. To this solution was added 53.59 g ferric nitrate nonahydrate salt, Fe(NO 3 ) 3 -9H 2 O (ACS reagent, Alfa Aesar reagent #33315, CAS #7782-61-8), equivalent to 13.82 wt% Fe. The molar ratio of Fe/phosphate in this mixture was 1/1 and the equivalent solids level [as FePO 4 ] was 23.2 wt%.
- Example 8 Low Temperature Calcium Phosphate Powders An aqueous solution of 19.41 g 50 wt% H 3 PO 2 was combined with 5.00 g distilled water to form a clear, colorless solution contained in a 250 ml Pyrex beaker. To this solution was added 34.72 g Ca(NO 3 ) 2 .4H 2 O. The molar ratio of Ca/phosphate in this mixture was 1/1 and the equivalent solids level [as CaHPO 4 ] was 33.8 wt%. Endothermic dissolution of the calcium nitrate tetrahydrate proceeded under ambient temperature conditions, eventually forming a homogeneous solution once the sample warmed to room temperature. Warming of this solution above 25 °C initiated a vigorous exothermic reaction which resulted in the evolution of NO x (g) , rapid temperature increase of the sample to
- Example 3 was repeated using ten times the indicated weights of reagents.
- the reactants were contained in a 5-1/2" diameter Pyrex crystallizing dish on a hotplate/stirrer. The reactants were stirred continuously during the dissolution and reaction stages.
- the chemical reaction initiated by heating the solution to >25 °C resulted in the evolution of NO x (g) for several minutes with no apparent effect on the stability of the system, i.e. the solution remained clear and colorless with no evidence of solid formation.
- the reaction resumed with increased intensity resulting in the voluminous generation of NO x (g) and the rapid appearance of a pasty white solid material.
- the reaction vessel and product were both hot from the reaction exotherm. The product was cooled in air to a white crumbly solid which was stored in a polyethylene vial.
- Example 1 Warming of the solution above 25 °C initiated a vigorous exothermic reaction as described in Example 1. After approximately three minutes, the reaction was essentially complete leaving a moist, white, pasty solid.. Heat treatment and X-ray diffraction of this solid were conducted as described in Example 1. Following heat treatment in air at 500 °C for 0.5 hour, XRD indicated the solid to be composed of whitlockite as the primary phase along with hydroxyapatite as the secondary phase. There was no evidence for the formation of octacalcium phosphate (OCP), despite the initial sample stoichiometry. This result suggests that (a) alternate heat treatments are necessary to crystallize OCP and/or (b) excess Ca is present in the intermediate powder.
- OCP octacalcium phosphate
- Example 12 Low Temperature Calcium Phosphate Powders Example 11 was repeated except that no distilled water was used in preparation of the reaction mixture. Warming of the homogeneous solution above 25 °C initiated an exothermic reaction as described in Example 11. After approximately three minutes, the reaction was essentially complete leaving a moist, pasty, white solid. Heat treatment and X-ray diffraction of this solid were conducted as described in Example 1. Following heat treatment in air at 500 °C for 0.5 hour, XRD indicated the solid to be composed of calcium pyrophosphate (Ca 2 P 2 O 7 ).
- a total of 47.0 g of this solution was added, with rapid agitation, to an aqueous solution of 50 wt% sodium hypophosphite monohydrate, NaH 2 PO 2 -H 2 O (Alfa/Aesar reagent #14104, CAS #10039-56-2) also prepared by dissolving 250.0 g of the salt in 250.0 g distilled water.
- the sodium hypophosphite solution was equivalent to 44.80 wt% [PO 4 ] '3 .
- the clear, colorless solution of calcium nitrate and sodium hypophosphite was then diluted with 40.3 g distilled water .
- the molar ratio of Ca/phosphate in this mixture was 5/3, and the equivalent solids level [as Ca 5 (PO 4 ) 3 (OH) (hydroxyapatite)] was 10.0 wt%.
- the sample was hydrothermally treated using a 300 cc volume stirred high pressure bench reactor (Model no. 4561 Mini Reactor, Parr Instrument Co., Mo line, IL 61265) equipped with a temperature controller / digital tachometer unit (Model no. 4842, Parr Instrument Co.) and dial pressure gauge. All wetted parts of the reactor were fabricated from type 316 stainless steel.
- type 316SS is not the material of choice for inorganic acid systems such as the solution precursors used in this invention, since phosphoric acid can attack stainless steel at elevated temperatures and pressures.
- direct contact i.e. wetting
- the stirrer and thermocouple sheath were immersed in the reactant solutions and no corrosion was observed.
- the high nitrate ion concentration in the reactant mixture provided a passivating environment for the type 316SS.
- Example 1 A white precipitate was present in the glass liner.
- the solid was collected by vacuum filtration on a 0.45 micron membrane filter (Millipore, Inc., Bedford, MA, 01730), washed several times with distilled water, and dried at approximately 55 °C in a forced convection oven. X-ray diffraction of this solid was conducted as described in Example 1.
- Example 13 was repeated except that 40.3 g of 1.0 M NaOH solution was added with rapid stirring to the homogeneous solution of calcium nitrate and sodium hypophosphite instead of the distilled water. This base addition resulted in the formation of a milk white dispersion, presumably due to precipitation of Ca(OH) 2 .
- Example 13 The sample was hydrothermally processed as described in Example 13 with the temperature set point at 207 °C. The temperature ramp to 160 °C (25 minutes) was as indicated for Example 13. At 30 minutes into the run, an exotherm occurred causing the temperature of the reaction mixture to rise to a maximum of 221 °C within five minutes with a corresponding pressure increase to 370 psi. At 38 minutes into the experiment, the reactor was quenched to room temperature.
- the reaction product consisted of a small amount of white precipitate.
- the material was collected as described in Example 13.
- X-ray diffraction of the dried sample was conducted as described in Example 1.
- XRD results indicated the solid to be comprised of the same unidentifiable pattern (crystal phase) found in Example 13 and minor amounts of HAp - [Ca 5 (PO 4 ) 3 (OH)].
- a total of 47.0 g of a 50 wt% aqueous solution of calcium nitrate tetrahydrate was diluted with 53.0 g distilled water. Then, 6.00 g calcium hypophosphite salt, Ca(H 2 PO 2 ) 2 (Alfa/Aesar reagent #56168, CAS #7789-79-9), equivalent to 23.57 wt% Ca and 111.7 wt% [PO ] " ⁇ was slurried into the Ca(NO 3 ) 2 solution using rapid agitation. An unknown amount of the calcium hypophosphite remained undissolved in the room temperature sample. The solubility behavior of Ca(H 2 PO 2 ) 2 in the Ca(NO 3 ) 2 solution at elevated temperatures is unknown. The molar ratio of Ca/phosphate in this system was 1.91.
- Example 13 This sample was hydrothermally processed as described in Example 13 with the temperature set point at 212 °C. The temperature ramp to 200 °C was as indicated for Example 13. At 39 minutes into the run, an exotherm occurred causing the temperature of the reaction mixture to rise to a maximum of 252 °C within three minutes with a corresponding pressure increase to 640 psi. At 44 minutes into the experiment, the reactor was quenched to room temperature.
- the reaction product appeared as a voluminous white precipitate plus some suspended solids.
- the material was collected as described in Example 13.
- X-ray diffraction of the dried solid was conducted as described in Example 1.
- XRD showed the major peak at position 30.2° (2-theta) which indicated the solid to be monetite, CaHPO 4 .
- the unique crystal mo ⁇ hology is depicted in the scanning electron micrograph representation in Figure 2.
- RPR and HYPR powders are useful in the formation of self-setting calcium phosphate cements for the repair of dental and orthopaedic defects.
- specific components and solubilizing liquids can also be added to form the precursor bone mineral constructs of this invention.
- Example 17 - Cement Compositions A stock solution was formed with the approximately 7 M NaOH solution used in Example 1 and 1.0%> polyacrylic acid (PAA). PAA is used as a chelating setting additive and wetting agent. The above solution was used with several powder combinations to form setting cements. A 50/50 powder mix of HYPR monetite [Example 15] and RPR ⁇ -TCP -HAp(CO 3 ) [Example 3], approximately 0.7 g, was mixed with a glass spatula on a glass plate with 0.39 g of the 1% PAA-NaOH solution (powder to liquid ratio
- HYPR monetite HYdrothermally PRocessed monetite (CaHPO 4 ).
- RPR Reduction-oxidation Precipitation Reaction.
- Example 37 Low Temperature Yttrium Phosphate Powders An aqueous solution of 14.36 g of 50 wt.% H 3 PO 2 was diluted with 5.00 g distilled water to form a clear, colorless solution contained in a 250 ml fluoropolymer resin beaker on a hotplate/magnetic stirrer. Added to this solution was 41.66 g yttrium nitrate hexahydrate salt, Y(NO 3 ) 3 -6H 2 O (Alfa Aesar reagent #12898, CAS # 13494-98-9), equivalent to 23.21 wt% Y.
- oxidizing and reducing agents are listed. Any of the listed oxidants can be reacted with any of the listed reducing agents and, indeed, blends, of each may be employed. Appropriate stoichiometry will be employed such that the aforementioned reaction is caused to proceed. Also specified are possible additives and fillers to the reactions.
- the expected products are given as are some of the expected fields of application for the products. All of the following are expected generally to follow the methodology of some or all of the foregoing Examples.
- the minerals prepared above may be used in a wide variety of applications. Examples of these applications may include, but are not limited to, use as pigments, phosphors, fluorescing agents, paint additives, synthetic gems, chromatography media, gas scrubber media, filtration media, bioseparation media, zeolites, catalysts, catalytic supports, ceramics, glasses, glass-ceramics, cements, electronic ceramics, piezoelectric ' ceramics, bioceramics, roofing granules, protective coatings, barnacle retardant coating, waste' solidification, nuclear waste solidification, abrasives, polishing agents, polishing pastes, radiopharmaceuticals, medical imaging and diagnostics agents, drug delivery, excipients, tabletting excipients, bioactive dental and orthopaedic materials and bioactive coatings, composite fillers, composite additives, viscosity adjustment additives, paper finishing additives, optical coatings, glass coatings, optical filters, fertilizers, soil nutrient(s) additives.
- a piece of damp (as removed from the packaging) cellulose sponge (O-Cel-O TM , 3M Home and Commercial Care Division, P.O. Box 33068, St. Paul. MN 55133), trimmed to a block approximately 1.5"xl.5"x2.0", was immersed in the calcium nitrate + hypophosphorous acid solution and kneaded (alternately compressed and decompressed) to fully imbibe the reactant solution into the sponge.
- the approximately 4.5 cubic inch sponge block (approximately 3.5 g), thoroughly saturated with reactant solution (liquid uptake approximately 7 to 8 times the virgin sponge weight), was placed on a platinum plate in a laboratory furnace (Vulcan model 3-550, NEYTECH, Inc., 1280 Blue Hills Ave., Bloomfield, CT 06002) that was preheated to 500°C. After several seconds, a reaction commenced at the surface of the sponge with the evolution of red-brown fumes characteristic of NO x(g) . As the reaction proceeded from the surface to the interior of the sponge block, NO x(g) evolution continued and some reactant liquid exuded from the sponge and accumulated at the bottom of the Pt plate as a crusty white mass of solid.
- the cellulose sponge itself was consumed as the reaction progressed and the reactant mass attained the oven temperature. After thermal treatment at 500°C for 45 minutes, the sample was removed from the lab furnace. The sample had been converted to an inorganic replica of the original organic sponge structure.
- the vestigial structure represented a positive version of the original sponge structure with faithful replication of the cellular elements, porosity, and macrostructure.
- the vestigial mass was mottled gray suggesting the presence of some residual carbon in the structure due to incomplete burnout of the combustion products from the cellulose sponge matrix.
- the vestigial mass was fragile with very low apparent density, but it was robust enough to be handled as a coherent block of highly porous solid once it was removed from the exudate material.
- XRD X-ray diffraction
- Example 39 The material from Example 39 was fired under a variety of conditions in order to (1) eliminate residual carbon from the structure and (2) attempt to promote sintering reactions in order to strengthen the inorganic sponge matrix.
- the samples were fired on Pt plates in a Lindberg model 51333 box furnace (Lindberg/Blue M, Inc., 304 Hart St., Watertown, WI 53094) equipped with a Lindberg series 59000 control console.
- the following table summarizes these results:
- a solution was prepared as described in Example 39 using 9.70 g 50wt% H 3 PO 2 , no deionized water, and 17.38 g Ca(NO 3 ) 2 4H 2 O to obtain a molar ratio of [Ca] 2 7[PO 4 ] "3 of 1.0 and an equivalent solids level [as CaHPO 4 ] of 36.92 wt%.
- a small block of damp O-Cel-OTM sponge (as removed from the packaging) was fully imbibed with the reactant solution, set in a porcelain crucible, and placed into a Vulcan lab oven preheated to 500°C. After 1 hour at 500°C, the mottled gray sample was refired at 800°C (Vulcan furnace) for 15 minutes.
- the inorganic sponge mass was very fragile, but it was robust enough to be handled as a coherent block of low density, highly porous material.
- An XRD pattern (Figure 18) was obtained from a packed powder sample prepared as described in Example 39. Peak analysis indicated the solid to consist of neodymium phosphate, NdPO 4 (PDF 25-1065).
- the sample was first fired at 500°C for 1 hour and then at 800°C for 15 minutes.
- the inorganic sponge sample was white at the outside of the inorganic sponge mass and light gray in the interior (due to residual carbon).
- the inorganic sponge mass could be handled as a coherent block of low density, highly porous material.
- An XRD pattern ( Figure 19) was obtained from a packed powder sample prepared as described in Example 39. Peak analysis indicated the solid to consist of aluminum phosphate, AlPO 4 (PDF 11-0500).
- a piece of the inorganic sponge material from Example 39 was immersed in molten paraffin wax (CAS #8002-74-2) (Northland Canning Wax, Conros Co ⁇ ., Detroit, MI 48209) maintained at >80°C so as to imbibe the porous structure.
- the inorganic sponge, wetted with molten wax, was removed from the molten wax and allowed to cool at room temperature.
- Most of the formerly open porosity of the inorganic sponge material was filled with solidified paraffin wax.
- a piece of the inorganic sponge material from Example 39 was immersed in a solution prepared by dissolving 7.1 g food-grade gelatin (CAS # 9000-70-0) (Knox Unflavored Gelatin, Nabisco Inc., East Hanover, NJ 07936) in 100.0 g deionized water at approximately 90°C.
- the inorganic sponge material readily imbibed the warm gelatin solution and, after several minutes, the largely intact piece of inorganic sponge material was carefully removed from the solution and allowed to cool and dry overnight at room temperature.
- the gelatin solution gelled on cooling (bloom strength unknown) and imparted additional strength and improved handling properties to the inorganic sponge material.
- the material exhibited considerable improvement in compression strength and a dramatically reduced tendency to shed particulate debris when cut with a knife or fine-toothed saw. It is presumed that the film- forming tendency of the gelatin on drying induced compressive forces on the internal cellular elements of the inorganic sponge material, thereby strengthening the overall structure.
- Cylindrical plugs could be cored from pieces of the air dried gelatin-treated inorganic sponge material using hollow punch tools ranging from 1/2 inch down to 1/8 inch in diameter.
- Figure 20 is a SEM of the air-dried gelatin treated inorganic sponge, which was prepared as described in Example 39. A comparison of this SEM with that of the initial cellulose sponge material ( Figure 12) shows how faithfully the sponge micro- and macrostructure has been replicated in the inorganic sponge material.
- Figure 21 is a SEM of sheep trabecular bone. The highly porous macrostructure of sheep trabecular bone is representative of the anatomical structure of cancellous bone of higher mammals, including humans.
- the sample of sheep trabecular bone was prepared for SEM analysis by sputter coating (as described in Example 39) a cross-sectional cut from a desiccated sheep humerus.
- Figure 22 is a higher magnification SEM of the air-dried gelatin treated inorganic sponge depicted in Figure 20. From this SEM micrograph, the presence of meso- and microporosity in the calcium phosphate matrix is readily apparent.
- a rectangular block approximately 1/4 inch x 1/2 inch x 3/4 inch was cut from a piece of damp (as removed from the packaging) O-Cel-OTM cellulose sponge. This sponge piece was trimmed as necessary so to completely fill the internal cavity of a titanium nitride (TiN)-coated box-like spinal implant cage (Stratech Medical, Inc.). The sponge insert was intentionally made slightly oversized to ensure good fit and retention in the cage assembly. The cellulose sponge block was fully imbibed with a reactant solution prepared as described in Example 39. The solution-saturated sponge insert was then inserted through the open side of the spinal cage assembly and manipulated to completely fill the interior cavity of the implant assembly.
- TiN titanium nitride
- the sponge-filled cage assembly sitting on a Pt plate, was placed in a laboratory oven preheated to 500°C and held at that temperature for 1 hour. After cooling to room temperature, the implant assembly was removed from the small amount of crusty white solid resulting from reactant solution which had exuded from the sponge insert and coated the surface of the implant.
- the TiN coating on the cage appeared unaffected by the treatment, and the internal chamber was filled with inorganic sponge material having a mottled gray appearance.
- the filled cage assembly was refired at 800°C for 30 minutes in an attempt to eliminate residual carbon from the inorganic sponge material. After cooling, examination of the implant assembly revealed that the TiN coating had been lost via oxidation, while the inorganic sponge material was completely white. There was excellent retention of the inorganic sponge material in the chamber of the spinal cage assembly.
- the plugs were intentionally made slightly oversized to ensure good fit and retention in the two chambers of the titanium spinal fusion cage assembly.
- the cylindrical sponge plugs were fully imbibed with a reactant solution prepared as described in Example 39 and the solution saturated sponge plugs were inserted through the open ends of the spinal cage assembly and manipulated to completely fill both of the internal chambers of the implant assembly. Despite the compliance of the solution- saturated sponge, there was almost no penetration of the sponge into the fenestrations of the implant.
- the sponge-filled cage assembly sitting on a Pt plate was placed in a laboratory oven preheated to 200°C. Immediately, a temperature ramp to 500°C was begun (duration of 16 minutes) followed by a 30 minute hold at 500°.
- the implant assembly was removed from the small amount of crusty white solid resulting from reactant solution which had exuded from the sponge pieces and coated the surface of the implant.
- the titanium cage appeared unaffected by the treatment, and the chambers were filled with inorganic sponge material having a mottled gray appearance.
- the filled cage assembly was refired at 700°C for 10 minutes in an attempt to eliminate residual carbon from the inorganic sponge material.
- examination of the implant assembly revealed that the surface of the titanium cage appeared to have undergone some oxidation as evidenced by its roughened texture, while the inorganic sponge material was white at the surface but still gray at the center of the mass.
- Example 51 Alternative Templates A reactant solution was prepared as described in Example 39. A variety of shapes, including disks, squares, and triangles, were cut from a sheet of 3/32 inch thick "Normandy compressed sponge" (Spontex, Inc., P.O. Box 561, Santa Fe Pike, Columbia, TN 38402) using either scissors or hollow punches. This compressed cellulose sponge is manufactured to have a smaller median pore size and a narrower pore size distribution than either of the commercially available household sponges (O-Cel-OTM or MarquisTM) used in Examples 39-50. This compressed sponge also has low ash levels ( ⁇ 0.1 wt% when burned out according to the procedure mentioned in Example 50) indicating that it is washed essentially free of salts during fabrication.
- Normal compressed sponge Spontex, Inc., P.O. Box 561, Santa Fe Pike, Columbia, TN 38402
- This compressed cellulose sponge is manufactured to have a smaller median pore size and a narrower pore size distribution than either of the commercially
- the sponge is compressed into a sheet which, upon rewetting, expands to restore the original cellular sponge structure which, in the case of this particular example, is approximately 1 inch thick. Imbibation of water into the compressed sponge to saturation levels results in a weight increase of approximately 28 times over the dry sponge weight.
- the cut pieces of compressed sponge were fully imbibed with the reactant solution after which they swelled to form cylinders, cubes, and wedges. These solution saturated sponge articles, setting on Pt plates, were placed into a Vulcan model 3-550 oven preheated to 500°C and held at that temperature for 1 hour. After cooling, the inorganic sponge pieces were carefully removed from the considerable amount of crusty white solid resulting from the exudate material.
- the vestigial structures represented positive versions of the original sponge structures with faithful replication of the cellular elements and porosity.
- the vestigial masses were fragile with very low apparent density, but they were robust enough to be handled as coherent blocks of highly porous solid once they were removed from the exudate material.
- the inorganic sponge material was mottled gray, suggesting the presence of some residual carbon in the structure. After refiring the samples at 800°C (Vulcan furnace) for 15 minutes, the final inorganic sponge samples were completely white. The integrity of the various samples made from the controlled porosity cellulose sponge was improved over corresponding samples prepared from the commercial cellulose sponge materials.
- Figure 24 is a SEM of the Normandy compressed sponge expanded in deionized water and prepared for microscopy as described in Example 39.
- Pieces of the inorganic sponge material from Example 51 were immersed in a gelatin solution prepared as described in Example 46 except that 7.1 g of Knox gelatin was dissolved in 200 g deionized water rather than 100 g of deionized water.
- the inorganic sponge material readily imbibed the warm gelatin solution and, after several minutes, the largely intact pieces of inorganic sponge material were carefully removed from the solution and allowed to cool and dry at room temperature.
- Significant additional strength and improved handling properties were noted in the gelatin-treated inorganic sponge material after the gelatin was allowed to thoroughly dry for several days. The material exhibited considerable improvement in compression strength and a dramatically reduced tendency to shed particulate debris when cut with a knife or fine-toothed saw.
- Figure 25 is a SEM of the air-dried gelatin treated inorganic sponge which was prepared as described above. A comparison of this SEM with that of the initial cellulose sponge material ( Figure 24) shows how faithfully the sponge micro- and macrostructure has been replicated in the polymer coated inorganic sponge material.
- Example 39 Several pieces of the inorganic sponge material from Example 39 were immersed in a 50 wt% solution of disodium glycerophosphate hydrate prepared by dissolving 10.0 g C 3 H 7 O 6 PNa 2 (Sigma Chemical Co. reagent G-6501, CAS # 154804-51- 0), equivalent to 65.25 wt% as "Na 2 PO 4 ", in 10.0 g deionized water.
- the inorganic sponge material readily imbibed the disodium glycerophosphate solution and, after several minutes, the largely intact pieces of saturated inorganic sponge material were carefully removed from the solution.
- the wetted pieces, setting on a Pt plate, were placed in a Vulcan model 3-550 oven preheated to 150°C.
- a reactant solution was prepared as described in Example 39. Disks were cut from a sheet of 3/32 inch thick Normandy compressed sponge using a 3/8 inch diameter hollow punch and a model no. 3393 Carver hydraulic press (Carver Inc., 1569 Morris St.,
- the pieces were very robust at this point, there was little or no warpage or slumping, and they could be handled and even abraded to shape the pieces and to remove asperities and any adherent solid resulting from the exuded liquid.
- the dried, solid-filled cylindrical sponge pieces were arrayed in a rectangular alumina crucible (2-1/2" W x 6" L x 1/2" D) and placed in a furnace preheated to 500 °C. The furnace temperature was ramped at 40°C/minute to 800°C and held at 800°C for 45 minutes.
- the resultant cylindrical white porous inorganic sponge samples were robust and exhibited strengths qualitatively similar to those attained from the fully dried gelatin-treated samples prepared as described in Example 52.
- porous calcium phosphate scaffolds prepared as described in Example 55, are instantly wetted by water, aqueous solutions, alcohols, and other hydrophilic liquids in distinct contrast to the gradual rewetting of the gelatin-treated scaffold structure (Example 53). Blood readily wicks into the porous calcium phosphate bodies without obvious detrimental effects. It is believed that cells, e.g., fibroblasts, mesenchymal, stromal, marrow, and stem cells, as well as protein-rich plasma and combinations of the aforementioned cells can also be imbibed into the porous structures.
- cells e.g., fibroblasts, mesenchymal, stromal, marrow, and stem cells, as well as protein-rich plasma and combinations of the aforementioned cells can also be imbibed into the porous structures.
- Highly porous calcium phosphate cylindrical plugs were prepared as described in Example 55 starting with 10 mm discs punched from Normandy compressed sponge.
- the cylindrical porous bodies were dry heat sterilized in DualPeelTM self seal pouches (distributed by Allegiance Healthcare Corp., McGaw Park, IL 60085) at 125 °C for 8 hours.
- Figure 27 depicts implantation of the cylinder into the canine bone.
- the mineral phase of human bone consists primarily of compositionally modified, poorly crystalline hydroxyapatite, Ca 5 (PO 4 ) 3 (OH).
- the hydroxyapatite crystallographic structure is partially substituted by carbonate anions (7.4 wt.%) as well as by metal cations present at fractional wt.% levels.
- a reactant solution was prepared by combining 7.88 g 50 wt.% hypophosphorous acid, H 3 PO 2 , with 5.00 g deionized water in a 250 ml Pyrex beaker. To this solution was added 22.51 g calcium nitrate tetrahydrate salt, Ca(NO 3 ) 2 4H 2 O; plus 0.33 g sodium nitrate salt, NaNO 3 (Fisher Certified ACS reagent #S343-500, CAS #7631-99-4), equivalent to 27.05 wt.% Na; plus 0.74 g magnesium nitrate hexahydrate salt,
- the equivalent solids level (as cation substituted hydroxyapatite) was 27.39 wt.% and the target solid composition was 38.19 wt.% Ca, 0.90 wt.% Na, 0.70 wt.% Mg, 0.10 wt.% Zn, 56.72 wt.% PO 4 , and 3.39 wt.% OH.
- the inorganic porous material prepared in Examples 39 through 57 can be utilized in a variety of applications. These applications include, but are not limited to: bone or teeth replacement, filters, catalytic converters, catalytic substrates, bioseparations media, pharmaceutical excipients, gas scrubber media, piezoelectric ceramics, pharmaceutical drug delivery systems, or aerators. As the examples illustrate, the composition can be easily tailored to accommodate the particular end use without the concerns of extensive material preparation such as purification or particle size treatment. Further, the porous inorganic material can be formed into a variety of practical shapes without elaborate tools or machining.
- the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof and, accordingly, reference should be made to the appended claims rather than to the foregoing specifications, as indicating the scope of the invention.
Abstract
Description
Claims
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MXPA01007552A MXPA01007552A (en) | 1999-01-26 | 2000-01-26 | Inorganic shaped bodies and methods for their production and use. |
AU26245/00A AU767685B2 (en) | 1999-01-26 | 2000-01-26 | Inorganic shaped bodies and methods for their production and use |
CA002359488A CA2359488C (en) | 1999-01-26 | 2000-01-26 | Inorganic shaped bodies and methods for their production and use |
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Cited By (19)
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---|---|---|---|---|
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WO2005074614A2 (en) | 2004-02-03 | 2005-08-18 | Vita Special Purpose Corporation | Bone graft substitute |
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WO2008002682A2 (en) * | 2006-06-29 | 2008-01-03 | Orthovita, Inc. | Bioactive bone graft substitute |
WO2009001318A1 (en) * | 2007-06-27 | 2008-12-31 | Alma Mater Studiorum - Universita' Di Bologna | Porous support of calcium phosphate cementitious material and its use in fluidic instruments |
WO2009095700A1 (en) * | 2008-02-01 | 2009-08-06 | Apatech Ltd. | Porous biomaterial |
US7910124B2 (en) | 2004-02-06 | 2011-03-22 | Georgia Tech Research Corporation | Load bearing biocompatible device |
WO2011084731A1 (en) * | 2009-12-21 | 2011-07-14 | Orthovita, Inc. | Strontium-doped calcium phosphate bone graft materials |
US8002830B2 (en) | 2004-02-06 | 2011-08-23 | Georgia Tech Research Corporation | Surface directed cellular attachment |
US8163032B2 (en) | 2002-06-13 | 2012-04-24 | Kensey Nash Bvf Technology, Llc | Devices and methods for treating defects in the tissue of a living being |
US9155543B2 (en) | 2011-05-26 | 2015-10-13 | Cartiva, Inc. | Tapered joint implant and related tools |
US9220595B2 (en) | 2004-06-23 | 2015-12-29 | Orthovita, Inc. | Shapeable bone graft substitute and instruments for delivery thereof |
US9907663B2 (en) | 2015-03-31 | 2018-03-06 | Cartiva, Inc. | Hydrogel implants with porous materials and methods |
US10350072B2 (en) | 2012-05-24 | 2019-07-16 | Cartiva, Inc. | Tooling for creating tapered opening in tissue and related methods |
US10758374B2 (en) | 2015-03-31 | 2020-09-01 | Cartiva, Inc. | Carpometacarpal (CMC) implants and methods |
CN111721630A (en) * | 2020-07-08 | 2020-09-29 | 中建四局第三建设有限公司 | Piezoelectric solidified soil for in-situ detection of sludge solidification and preparation method thereof |
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Families Citing this family (162)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040081704A1 (en) * | 1998-02-13 | 2004-04-29 | Centerpulse Biologics Inc. | Implantable putty material |
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
DE19940717A1 (en) * | 1999-08-26 | 2001-03-01 | Gerontocare Gmbh | Resorbable bone replacement and bone augmentation material |
AU2001231264A1 (en) | 2000-01-31 | 2001-08-07 | Advanced Research And Technology Institute, Inc. | Composite biomaterial including anisometric calcium phosphate reinforcement particles and related methods |
US8545786B2 (en) * | 2000-09-22 | 2013-10-01 | Colorado School Of Mines | Manufacture of porous net-shaped materials comprising alpha or beta tricalcium phosphate or mixtures thereof |
US6736799B1 (en) * | 2000-10-24 | 2004-05-18 | Vita Licensing, Inc. | Delivery device for biological composites and method of preparation thereof |
US7045125B2 (en) * | 2000-10-24 | 2006-05-16 | Vita Special Purpose Corporation | Biologically active composites and methods for their production and use |
US7052517B2 (en) * | 2000-10-24 | 2006-05-30 | Vita Special Purpose Corporation | Delivery device for biological composites and method of preparation thereof |
US20020114795A1 (en) | 2000-12-22 | 2002-08-22 | Thorne Kevin J. | Composition and process for bone growth and repair |
US6949251B2 (en) * | 2001-03-02 | 2005-09-27 | Stryker Corporation | Porous β-tricalcium phosphate granules for regeneration of bone tissue |
US6478822B1 (en) * | 2001-03-20 | 2002-11-12 | Spineco, Inc. | Spherical spinal implant |
AU2002245979A1 (en) * | 2001-04-05 | 2002-10-21 | Universite Laval | Process for making protein delivery matrix and uses thereof |
WO2002083194A1 (en) * | 2001-04-12 | 2002-10-24 | Therics, Inc. | Method and apparatus for engineered regenerative biostructures |
US6913844B2 (en) * | 2001-06-29 | 2005-07-05 | Porvair Corporation | Method for humidifying reactant gases for use in a fuel cell |
US7238203B2 (en) * | 2001-12-12 | 2007-07-03 | Vita Special Purpose Corporation | Bioactive spinal implants and method of manufacture thereof |
US20040127563A1 (en) * | 2002-03-22 | 2004-07-01 | Deslauriers Richard J. | Methods of performing medical procedures which promote bone growth, compositions which promote bone growth, and methods of making such compositions |
TW200400062A (en) | 2002-04-03 | 2004-01-01 | Mathys Medizinaltechnik Ag | Kneadable, pliable bone replacement material |
US20040002770A1 (en) * | 2002-06-28 | 2004-01-01 | King Richard S. | Polymer-bioceramic composite for orthopaedic applications and method of manufacture thereof |
DE10243132B4 (en) * | 2002-09-17 | 2006-09-14 | Biocer Entwicklungs Gmbh | Anti-infective, biocompatible titanium oxide coatings for implants and methods of making them |
FR2850282B1 (en) | 2003-01-27 | 2007-04-06 | Jerome Asius | INJECTABLE IMPLANT BASED ON CERAMIC FOR THE FILLING OF WRINKLES, CUTANEOUS DEPRESSIONS AND SCARS, AND ITS PREPARATION |
US20040180091A1 (en) * | 2003-03-13 | 2004-09-16 | Chang-Yi Lin | Carbonated hydroxyapatite-based microspherical composites for biomedical uses |
US7824444B2 (en) * | 2003-03-20 | 2010-11-02 | Spineco, Inc. | Expandable spherical spinal implant |
WO2004098457A1 (en) * | 2003-04-30 | 2004-11-18 | Therics, Inc. | Bone void filler and method of manufacture |
US20050046067A1 (en) * | 2003-08-27 | 2005-03-03 | Christopher Oriakhi | Inorganic phosphate cement compositions for solid freeform fabrication |
US20050085922A1 (en) * | 2003-10-17 | 2005-04-21 | Shappley Ben R. | Shaped filler for implantation into a bone void and methods of manufacture and use thereof |
WO2005057165A2 (en) * | 2003-12-05 | 2005-06-23 | The Regents Of The University Of Michigan | Biodegradable/bioresorbable tissue augmentation/reconstruction device |
AU2012244219B2 (en) * | 2004-02-03 | 2014-07-24 | Stryker Corporation | Bone graft substitute |
WO2005094553A2 (en) | 2004-03-24 | 2005-10-13 | Doctor's Research Group, Inc. | Compositions for promoting bone growth and methods thereof |
US20050234545A1 (en) * | 2004-04-19 | 2005-10-20 | Yea-Yang Su | Amorphous oxide surface film for metallic implantable devices and method for production thereof |
US7785615B2 (en) * | 2004-05-28 | 2010-08-31 | Cordis Corporation | Biodegradable medical implant with encapsulated buffering agent |
US7803182B2 (en) * | 2004-05-28 | 2010-09-28 | Cordis Corporation | Biodegradable vascular device with buffering agent |
WO2006050493A2 (en) | 2004-11-03 | 2006-05-11 | The Regents Of The University Of Michigan | Biodegradable implant for intertransverse process fusion |
US20060110422A1 (en) * | 2004-11-19 | 2006-05-25 | Tas Ahmet C | Conversion of calcite powders into macro- and microporous calcium phosphate scaffolds for medical applications |
US20060129215A1 (en) * | 2004-12-09 | 2006-06-15 | Helmus Michael N | Medical devices having nanostructured regions for controlled tissue biocompatibility and drug delivery |
US20060198863A1 (en) * | 2005-03-03 | 2006-09-07 | Musculoskeletal Transplant Foundation | Ceramic composition for filling bone defects |
US7621963B2 (en) * | 2005-04-13 | 2009-11-24 | Ebi, Llc | Composite bone graft material |
US20060233849A1 (en) * | 2005-04-13 | 2006-10-19 | Simon Bruce J | Composite bone graft material |
DE102005019000A1 (en) * | 2005-04-22 | 2006-10-26 | Degussa Ag | Catalytically coated support, process for its preparation and thus equipped reactor and its use |
US9101436B2 (en) * | 2005-10-21 | 2015-08-11 | Ada Foundation | Dental and endodontic filling materials and methods |
US9259439B2 (en) * | 2005-10-21 | 2016-02-16 | Ada Foundation | Dual-phase cement precursor systems for bone repair |
EP1945233B1 (en) * | 2005-10-21 | 2017-03-29 | Ada Foundation | Dual-phase cement precursor systems for bone repair |
JP5523709B2 (en) * | 2005-11-14 | 2014-06-18 | バイオメット・3アイ・エルエルシー | Method of depositing discrete nanoparticles on an implant surface |
US8690957B2 (en) | 2005-12-21 | 2014-04-08 | Warsaw Orthopedic, Inc. | Bone graft composition, method and implant |
US7941875B1 (en) * | 2006-02-27 | 2011-05-17 | Brown Medical Industries | Trabecular matrix like protectors and method |
DE102006013854B4 (en) * | 2006-03-23 | 2010-08-19 | Heraeus Kulzer Gmbh | Use of a hydroxyapatite-forming material having a bioactive effect as a dental material |
US20070224235A1 (en) | 2006-03-24 | 2007-09-27 | Barron Tenney | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
CN101495065B (en) * | 2006-04-25 | 2014-07-23 | 泰里福来克斯医学公司 | Calcium phosphate polymer composite and method |
BRPI0601618A (en) * | 2006-05-08 | 2008-01-08 | Ct Brasileiro De Pesquisa Fisi | process for covering interconnected porous substrate, synthesis intermediate and porous product obtained |
BRPI0712442A8 (en) * | 2006-05-31 | 2017-10-24 | Unifrax I Llc | SPARE THERMAL INSULATION PLATE |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
WO2008002778A2 (en) | 2006-06-29 | 2008-01-03 | Boston Scientific Limited | Medical devices with selective coating |
US20080112874A1 (en) * | 2006-08-31 | 2008-05-15 | Burkes Douglas E | Method for producing calcium phosphate powders using an auto-ignition combustion synthesis reaction |
WO2008033711A2 (en) | 2006-09-14 | 2008-03-20 | Boston Scientific Limited | Medical devices with drug-eluting coating |
US8968797B2 (en) | 2006-09-25 | 2015-03-03 | Orthovita, Inc. | Bioactive load-bearing composites |
US8602780B2 (en) * | 2006-10-16 | 2013-12-10 | Natural Dental Implants, Ag | Customized dental prosthesis for periodontal or osseointegration and related systems and methods |
US9539062B2 (en) | 2006-10-16 | 2017-01-10 | Natural Dental Implants, Ag | Methods of designing and manufacturing customized dental prosthesis for periodontal or osseointegration and related systems |
US8454362B2 (en) * | 2006-10-16 | 2013-06-04 | Natural Dental Implants Ag | Customized dental prosthesis for periodontal- or osseointegration, and related systems and methods |
US10426578B2 (en) | 2006-10-16 | 2019-10-01 | Natural Dental Implants, Ag | Customized dental prosthesis for periodontal or osseointegration and related systems |
US7708557B2 (en) * | 2006-10-16 | 2010-05-04 | Natural Dental Implants Ag | Customized dental prosthesis for periodontal- or osseointegration, and related systems and methods |
ES2729425T3 (en) | 2006-10-24 | 2019-11-04 | Biomet 3I Llc | Deposition of discrete nanoparticles on a nanostructured surface of an implant |
US9943410B2 (en) | 2011-02-28 | 2018-04-17 | DePuy Synthes Products, Inc. | Modular tissue scaffolds |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US7718616B2 (en) | 2006-12-21 | 2010-05-18 | Zimmer Orthobiologics, Inc. | Bone growth particles and osteoinductive composition thereof |
US20080206562A1 (en) * | 2007-01-12 | 2008-08-28 | The Regents Of The University Of California | Methods of generating supported nanocatalysts and compositions thereof |
US7713897B2 (en) * | 2007-02-27 | 2010-05-11 | Corning Incorporated | Ceramic materials for 4-way and NOx adsorber and method for making same |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
DE102007030585A1 (en) | 2007-06-27 | 2009-01-02 | Siemens Ag | Method for producing a ceramic layer on a component |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
EP2014256A1 (en) * | 2007-07-12 | 2009-01-14 | Straumann Holding AG | Composite bone repair material |
JP2010533563A (en) | 2007-07-19 | 2010-10-28 | ボストン サイエンティフィック リミテッド | Endoprosthesis with adsorption inhibiting surface |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US8221822B2 (en) | 2007-07-31 | 2012-07-17 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
JP2010535541A (en) | 2007-08-03 | 2010-11-25 | ボストン サイエンティフィック リミテッド | Coating for medical devices with large surface area |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
EP2222348B1 (en) | 2007-12-21 | 2013-07-03 | RTI Biologics, Inc. | Osteoinductive putties and methods of making and using such putties |
EP2234559A1 (en) * | 2008-01-09 | 2010-10-06 | Innovative Health Technologies, Llc | Implant pellets and methods for performing bone augmentation and preservation |
WO2009097218A1 (en) | 2008-01-28 | 2009-08-06 | Biomet 3I, Llc | Implant surface with increased hydrophilicity |
KR101530671B1 (en) * | 2008-01-29 | 2015-06-23 | 삼성전기 주식회사 | Method for preparing oxide nano phosphors |
US20090227503A1 (en) * | 2008-02-07 | 2009-09-10 | University Of Rochester | Parathyroid hormone treatment for enhanced allograft and tissue-engineered reconstruction of bone defects |
US8119057B2 (en) * | 2008-02-19 | 2012-02-21 | University Of Central Florida Research Foundation, Inc. | Method for synthesizing bulk ceramics and structures from polymeric ceramic precursors |
US20140031944A1 (en) * | 2008-03-18 | 2014-01-30 | Yoh Sawatari | Cylindrical graft and method for preparing a recipient site and implanting a cylindrical graft into alveolar jaw bone |
JP5581311B2 (en) | 2008-04-22 | 2014-08-27 | ボストン サイエンティフィック サイムド,インコーポレイテッド | MEDICAL DEVICE HAVING INORGANIC MATERIAL COATING AND MANUFACTURING METHOD THEREOF |
WO2009132176A2 (en) | 2008-04-24 | 2009-10-29 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
WO2009155328A2 (en) | 2008-06-18 | 2009-12-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8293048B2 (en) * | 2008-09-02 | 2012-10-23 | Weifeng Fei | Methods for synthesizing bulk, composite and hybrid structures from polymeric ceramic precursors as well as other polymeric substances and compounds |
WO2010036520A1 (en) * | 2008-09-26 | 2010-04-01 | Wisconsin Alumni Research Foundation | Mesoporous metal oxide materials for phosphoproteomics |
US8709149B2 (en) | 2008-11-12 | 2014-04-29 | Ossdsign Ab | Hydraulic cements, methods and products |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US20100168798A1 (en) | 2008-12-30 | 2010-07-01 | Clineff Theodore D | Bioactive composites of polymer and glass and method for making same |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8609127B2 (en) | 2009-04-03 | 2013-12-17 | Warsaw Orthopedic, Inc. | Medical implant with bioactive material and method of making the medical implant |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US9399086B2 (en) * | 2009-07-24 | 2016-07-26 | Warsaw Orthopedic, Inc | Implantable medical devices |
WO2011075580A1 (en) | 2009-12-18 | 2011-06-23 | Howmedica Osteonics Corp. | Post irradiation shelf-stable dual paste direct injectable bone cement precursor systems and methods of making same |
US8778378B2 (en) | 2009-12-21 | 2014-07-15 | Orthovita, Inc. | Bioactive antibacterial bone graft materials |
US8994666B2 (en) * | 2009-12-23 | 2015-03-31 | Colin J. Karpfinger | Tactile touch-sensing interface system |
WO2015147923A1 (en) | 2010-03-03 | 2015-10-01 | Novabone Products, Llc | Kit for delivering bone grafting materials |
WO2011109581A1 (en) | 2010-03-03 | 2011-09-09 | Novabone Products, Llc | Devices and methods for the regeneration of bony defects |
US9144629B2 (en) | 2010-03-03 | 2015-09-29 | Novabone Products, Llc | Ionically crosslinked materials and methods for production |
EP2544627B1 (en) | 2010-03-10 | 2018-05-02 | OssDsign AB | Implants for correcting tissue defects |
US8641418B2 (en) | 2010-03-29 | 2014-02-04 | Biomet 3I, Llc | Titanium nano-scale etching on an implant surface |
US9265857B2 (en) | 2010-05-11 | 2016-02-23 | Howmedica Osteonics Corp. | Organophosphorous, multivalent metal compounds, and polymer adhesive interpenetrating network compositions and methods |
US8251837B2 (en) | 2010-08-11 | 2012-08-28 | Nike, Inc. | Floating golf ball |
EP2637983B1 (en) | 2010-11-10 | 2018-12-26 | Stryker European Holdings I, LLC | Process for the preparation of a polymeric bone foam |
JP2013542837A (en) | 2010-11-15 | 2013-11-28 | ジンマー オーソバイオロジクス,インコーポレイティド | Bone void filler |
US8551525B2 (en) | 2010-12-23 | 2013-10-08 | Biostructures, Llc | Bone graft materials and methods |
US8765189B2 (en) | 2011-05-13 | 2014-07-01 | Howmedica Osteonic Corp. | Organophosphorous and multivalent metal compound compositions and methods |
US9463046B2 (en) | 2011-08-22 | 2016-10-11 | Ossdsign Ab | Implants and methods for using such implants to fill holes in bone tissue |
US20130066327A1 (en) | 2011-09-09 | 2013-03-14 | Håkan Engqvist | Hydraulic cement compositions with low ph methods, articles and kits |
US8591645B2 (en) | 2011-09-09 | 2013-11-26 | Ossdsign Ab | Hydraulic cements with optimized grain size distribution, methods, articles and kits |
KR101213355B1 (en) * | 2011-12-27 | 2012-12-18 | 오스템임플란트 주식회사 | Dental implant improving initial stability and the method for manufacturing the same |
US20130202670A1 (en) | 2012-02-03 | 2013-08-08 | Orthovita, Inc. | Bioactive antibacterial bone graft materials containing silver |
US10399907B2 (en) | 2012-03-02 | 2019-09-03 | Dynamic Material Systems, LLC | Ceramic composite structures and processing technologies |
US9764987B2 (en) | 2012-03-02 | 2017-09-19 | Dynamic Material Systems, LLC | Composite ceramics and ceramic particles and method for producing ceramic particles and bulk ceramic particles |
US9944021B2 (en) | 2012-03-02 | 2018-04-17 | Dynamic Material Systems, LLC | Additive manufacturing 3D printing of advanced ceramics |
ES2671740T3 (en) | 2012-03-20 | 2018-06-08 | Biomet 3I, Llc | Treatment surface for an implant surface |
US9539069B2 (en) | 2012-04-26 | 2017-01-10 | Zimmer Dental, Inc. | Dental implant wedges |
WO2014019083A1 (en) * | 2012-07-30 | 2014-02-06 | Sunnybrook Health Sciences Centre | Bone stabilization device and method of production |
ES2399000B1 (en) * | 2012-12-12 | 2014-01-28 | Biotechnology Institute I Mas D S.L. | Method to produce a porous structure of calcium polysphosphate |
US9913931B2 (en) | 2012-12-14 | 2018-03-13 | Ossdsign Ab | Cement-forming compositions, monetite cements, implants and methods for correcting bone defects |
US10076416B2 (en) | 2013-02-12 | 2018-09-18 | Ossdsign Ab | Mosaic implants, kits and methods for correcting bone defects |
US9220597B2 (en) | 2013-02-12 | 2015-12-29 | Ossdsign Ab | Mosaic implants, kits and methods for correcting bone defects |
US9604184B2 (en) | 2013-03-06 | 2017-03-28 | Orthovita, Inc. | Mixing system and valve assembly |
US9040093B2 (en) | 2013-03-13 | 2015-05-26 | Orthovita, Inc. | Bone graft materials containing calcium phosphate and chitosan |
US10118827B2 (en) | 2013-05-10 | 2018-11-06 | Reed A. Ayers | Combustion synthesis of calcium phosphate constructs and powders doped with atoms, molecules, ions, or compounds |
US9799883B2 (en) * | 2013-06-10 | 2017-10-24 | Shailesh Upreti | Bio-mineralized cathode and anode materials for electrochemical cell |
US9579205B2 (en) * | 2013-09-12 | 2017-02-28 | Ronen Shavit | Liners for medical joint implants with improved wear-resistance |
EP3305252B1 (en) | 2013-10-23 | 2019-05-15 | Stryker European Holdings I, LLC | Percutaneous bone graft delivery system |
US10188770B2 (en) * | 2014-06-26 | 2019-01-29 | Osstemimplant Co., Ltd. | Dental implant having enhanced early stability and method for manufacturing same |
WO2016024248A1 (en) | 2014-08-14 | 2016-02-18 | Ossdsign Ab | Bone implants for correcting bone defects |
EP3034033A1 (en) | 2014-12-16 | 2016-06-22 | Nobel Biocare Services AG | Dental implant |
WO2016127522A1 (en) * | 2015-02-09 | 2016-08-18 | 张英泽 | Porous bionic internal fixation apparatus for promoting fracture healing |
US10195305B2 (en) | 2015-03-24 | 2019-02-05 | Orthovita, Inc. | Bioactive flowable wash-out resistant bone graft material and method for production thereof |
US11331191B2 (en) | 2015-08-12 | 2022-05-17 | Howmedica Osteonics Corp. | Bioactive soft tissue implant and methods of manufacture and use thereof |
CA2938576A1 (en) | 2015-08-12 | 2017-02-12 | Howmedica Osteonics Corp. | Methods for forming scaffolds |
US10729548B2 (en) | 2016-05-02 | 2020-08-04 | Howmedica Osteonics Corp. | Bioactive soft tissue implant and methods of manufacture and use thereof |
WO2017089973A1 (en) | 2015-11-24 | 2017-06-01 | Ossdsign Ab | Bone implants and methods for correcting bone defects |
CN109642097A (en) | 2016-06-06 | 2019-04-16 | 尤尼弗瑞克斯 I 有限责任公司 | Fire resistant covering material and its manufacturing method containing low biopersistence fiber |
AU2017204355B2 (en) | 2016-07-08 | 2021-09-09 | Mako Surgical Corp. | Scaffold for alloprosthetic composite implant |
GB201614171D0 (en) * | 2016-08-18 | 2016-10-05 | Fitzbionics Ltd | An implant for repair of bone defects |
US10231846B2 (en) | 2016-08-19 | 2019-03-19 | Stryker European Holdings I, Llc | Bone graft delivery loading assembly |
US11540866B2 (en) * | 2017-03-29 | 2023-01-03 | Bone Solutions, Inc. | Implant of osteostimulative material |
US10722280B2 (en) * | 2017-03-29 | 2020-07-28 | Bone Solutions, Inc. | Implant of osteostimulative material |
DE102017106912A1 (en) * | 2017-03-30 | 2018-10-04 | Chemische Fabrik Budenheim Kg | Process for the preparation of Fe (II) P / Fe (II) MetP compounds |
DE102017106913A1 (en) | 2017-03-30 | 2018-10-04 | Chemische Fabrik Budenheim Kg | Process for the production of electrically conductive structures on a carrier material |
DE102017106911A1 (en) | 2017-03-30 | 2018-10-04 | Chemische Fabrik Budenheim Kg | Use of water-free Fe (II) compounds as radiation absorbers |
US10492839B2 (en) * | 2017-04-30 | 2019-12-03 | Felasfa Wodajo | Expandable osseointegration bone fixation apparatus for use in a variety of settings |
CN108404853A (en) * | 2018-04-13 | 2018-08-17 | 安徽瑞瑶环保科技有限公司 | A kind of rural scattered domestic sewage denitrogenation dephosphorizing composite filtering material and device |
CN109052358B (en) * | 2018-10-09 | 2020-10-27 | 湖南雅城新材料有限公司 | Preparation method of mesoporous-macroporous iron phosphate |
US11851772B2 (en) * | 2019-05-14 | 2023-12-26 | Tech Met, Inc. | Composition and method for creating nanoscale surface geometry on an implantable device |
CN110590351B (en) * | 2019-08-23 | 2021-05-25 | 中国科学院上海硅酸盐研究所 | Black bioactive ceramic powder and application thereof |
CN115996766A (en) * | 2020-06-02 | 2023-04-21 | 蒙诺苏尔有限公司 | Water-soluble fiber with post-processing modification and articles containing the same |
CN113813452B (en) * | 2021-09-22 | 2022-06-14 | 河南科技大学 | Construction method of 3D printing titanium alloy support with photo-thermal and temperature control warning functions |
USD955582S1 (en) | 2021-11-02 | 2022-06-21 | CraniUS LLC | Cranial implant |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2260538A (en) | 1991-10-15 | 1993-04-21 | Peter Gant | Porous ceramics |
US5296261A (en) | 1991-07-01 | 1994-03-22 | Saft | Method of manufacturing a sponge-type support for an electrode in an electrochemical cell |
US5338334A (en) | 1992-01-16 | 1994-08-16 | Institute Of Gas Technology | Process for preparing submicron/nanosize ceramic powders from precursors incorporated within a polymeric foam |
US5681872A (en) * | 1995-12-07 | 1997-10-28 | Orthovita, Inc. | Bioactive load bearing bone graft compositions |
WO1998031630A1 (en) | 1997-01-16 | 1998-07-23 | Orthovita, Inc. | Novel minerals and methods for their production and use |
Family Cites Families (177)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US390094A (en) * | 1888-09-25 | Device for hardening felt goods | ||
BE557975A (en) | 1956-06-04 | 1957-11-30 | ||
US3090094A (en) | 1961-02-21 | 1963-05-21 | Gen Motors Corp | Method of making porous ceramic articles |
US3443261A (en) | 1967-09-01 | 1969-05-13 | Fmc Corp | Prosthetic structures from microcrystalline collagen |
US4007020A (en) | 1970-02-02 | 1977-02-22 | Kaman Sciences Corporation | Refractory abrasive body containing chromium oxide and method of producing it |
US3679360A (en) | 1970-06-26 | 1972-07-25 | Nasa | Process for the preparation of brushite crystals |
US3732087A (en) | 1971-02-24 | 1973-05-08 | Corning Glass Works | Tetrasilicic mica glass-ceramic method |
BE793983A (en) | 1972-01-14 | 1973-05-02 | Foseco Int | MANUFACTURE OF NEW POROUS CERAMIC PRODUCTS |
BE793985A (en) | 1972-01-14 | 1973-05-02 | Foseco Int | TREATMENT OF PERMEABLE MATERIALS |
BE793984A (en) | 1972-01-14 | 1973-05-02 | Foseco Int | NEW MANUFACTURING OF POROUS CERAMIC PRODUCTS |
US3833386A (en) | 1972-07-07 | 1974-09-03 | Grace W R & Co | Method of prepairing porous ceramic structures by firing a polyurethane foam that is impregnated with inorganic material |
US3981736A (en) | 1973-05-23 | 1976-09-21 | Ernst Leitz G.M.B.H. | Biocompatible glass ceramic material |
US4045238A (en) | 1974-05-20 | 1977-08-30 | Avicon, Inc. | Regenerated cellulose sponge |
JPS5264199A (en) | 1975-11-21 | 1977-05-27 | Tokyo Ika Shika Daigakuchiyou | Artificial bone and dental root with sintered apatite and method of producing same |
US4149983A (en) | 1978-04-03 | 1979-04-17 | Merck & Co., Inc. | Antimicrobial additive for metal working fluids |
DE2917446A1 (en) | 1979-04-28 | 1980-11-06 | Merck Patent Gmbh | SURGICAL MATERIAL |
US4273131A (en) | 1979-06-18 | 1981-06-16 | Auburn Enterprises, Inc. | Surgical stylet |
US4328034A (en) | 1980-05-27 | 1982-05-04 | Ferguson Charles N | Foam composition and process |
US4491453A (en) | 1980-08-29 | 1985-01-01 | Dentsply Research & Development Corp. | Process for restoring teeth with visible light curable compositions |
DE8105177U1 (en) | 1981-02-25 | 1984-01-12 | Schuett Und Grundei Gmbh Medizintechnische Fabrikation, 2400 Luebeck | Implant as a replacement for cancellous bones |
US4673355A (en) | 1982-10-25 | 1987-06-16 | Farris Edward T | Solid calcium phosphate materials |
DE3241589A1 (en) | 1982-11-10 | 1984-05-17 | Pfaudler-Werke Ag, 6830 Schwetzingen | IMPLANTS AND METHOD FOR THE PRODUCTION THEREOF |
US4613627A (en) | 1982-12-13 | 1986-09-23 | Usg Acoustical Products Company | Process for the manufacture of shaped fibrous products and the resultant product |
US4609923A (en) | 1983-09-09 | 1986-09-02 | Harris Corporation | Gold-plated tungsten knit RF reflective surface |
US4612053A (en) | 1983-10-06 | 1986-09-16 | American Dental Association Health Foundation | Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements |
US4491517A (en) | 1983-12-23 | 1985-01-01 | W. S. Tyler Incorporated | Multi-dimensional screen |
US4619655A (en) | 1984-01-26 | 1986-10-28 | University Of North Carolina | Plaster of Paris as a bioresorbable scaffold in implants for bone repair |
US4775646A (en) | 1984-04-27 | 1988-10-04 | University Of Florida | Fluoride-containing Bioglass™ compositions |
DE3421157A1 (en) | 1984-06-07 | 1985-12-12 | Ernst Leitz Wetzlar Gmbh, 6330 Wetzlar | PLASTIC-BASED COMPOSITE FOR PROSTHETIC PURPOSES |
CA1264674A (en) | 1984-10-17 | 1990-01-23 | Paul Ducheyne | Porous flexible metal fiber material for surgical implantation |
US4888366A (en) | 1984-10-24 | 1989-12-19 | Collagen Corporation | Inductive collagen-based bone repair preparations |
US4563350A (en) | 1984-10-24 | 1986-01-07 | Collagen Corporation | Inductive collagen based bone repair preparations |
US4643982A (en) | 1984-12-05 | 1987-02-17 | Hoya Corporation | High-strength glass-ceramic containing anorthite crystals and process for producing the same |
JPS61201612A (en) | 1985-03-01 | 1986-09-06 | Kanto Kagaku Kk | Production of calcium-phosphorous series apatite |
US4711769A (en) | 1984-12-18 | 1987-12-08 | Kanto Kagaku Kabushiki Kaisha | Calcium-phosphorus-apatite having novel properties and process for preparing the same |
JPS6267451A (en) | 1985-09-20 | 1987-03-27 | Kanto Kagaku Kk | Packing agent for chromatography |
US4604097A (en) | 1985-02-19 | 1986-08-05 | University Of Dayton | Bioabsorbable glass fibers for use in the reinforcement of bioabsorbable polymers for bone fixation devices and artificial ligaments |
US5276068A (en) | 1985-03-29 | 1994-01-04 | Jeneric/Pentron, Inc. | Dental resin materials |
US4648124A (en) | 1985-04-04 | 1987-03-03 | The United States Of America As Represented By The Secretary Of The Air Force | Apparatus for locating passive intermodulation interference sources |
US4652534A (en) | 1985-04-30 | 1987-03-24 | Hoya Corporation | High-strength glass ceramic containing apatite crystals and a large quantity of wollastonite crystals and process for producing same |
US4851046A (en) | 1985-06-19 | 1989-07-25 | University Of Florida | Periodontal osseous defect repair |
US5034352A (en) | 1985-06-25 | 1991-07-23 | Lifecore Biomedical, Inc. | Calcium phosphate materials |
FR2583985B1 (en) | 1985-06-27 | 1988-08-05 | Nivarox Sa | STYLET FOR ELECTRODE IMPLANTABLE IN THE BODY |
JPS6210939A (en) | 1985-07-08 | 1987-01-19 | Nec Corp | Gain control system for avalanche photodiode |
JPS6239219A (en) | 1985-08-14 | 1987-02-20 | Tokuyama Soda Co Ltd | Oriented polyolefin film |
US4725234A (en) | 1985-08-15 | 1988-02-16 | Ethridge Edwin C | Alveolar bone grafting process with controlled surface active ceramics |
US4776890A (en) | 1985-12-18 | 1988-10-11 | Collagen Corporation | Preparation of collagen hydroxyapatite matrix for bone repair |
US4780450A (en) | 1985-12-20 | 1988-10-25 | The University Of Maryland At Baltimore | Physically stable composition and method of use thereof for osseous repair |
JPH0762674B2 (en) | 1986-03-07 | 1995-07-05 | 株式会社高研 | Chromatographic adsorbent, method for producing the same, and chromatographic column using the adsorbent |
US5236786A (en) | 1986-05-08 | 1993-08-17 | Lanxide Technology Company, Lp | Shaped ceramic composites with a barrier |
EP0269745B1 (en) | 1986-05-15 | 1993-08-18 | Sumitomo Cement Co. Ltd. | Bone prosthesis |
US4803075A (en) | 1986-06-25 | 1989-02-07 | Collagen Corporation | Injectable implant composition having improved intrudability |
US4891164A (en) | 1986-08-28 | 1990-01-02 | The Standard Oil Company | Method for separating and immobilizing radioactive materials |
US4889833A (en) | 1986-10-06 | 1989-12-26 | Kuraray Co., Ltd. | Granular inorganic moldings and a process for production thereof |
JP2543685B2 (en) | 1986-10-31 | 1996-10-16 | 旭光学工業株式会社 | Method for producing calcium phosphate |
US4737411A (en) | 1986-11-25 | 1988-04-12 | University Of Dayton | Controlled pore size ceramics particularly for orthopaedic and dental applications |
US4861733A (en) * | 1987-02-13 | 1989-08-29 | Interpore International | Calcium phosphate bone substitute materials |
US4812854A (en) | 1987-05-05 | 1989-03-14 | Harris Corp. | Mesh-configured rf antenna formed of knit graphite fibers |
US4859383A (en) | 1987-06-01 | 1989-08-22 | Bio Med Sciences, Inc. | Process of producing a composite macrostructure of organic and inorganic materials |
US4983573A (en) | 1987-06-09 | 1991-01-08 | E. I. Du Pont De Nemours And Company | Process for making 90° K. superconductors by impregnating cellulosic article with precursor solution |
US4868580A (en) | 1987-11-23 | 1989-09-19 | Lockheed Missiles & Space Company, Inc. | Radio-frequency reflective fabric |
DE3806448A1 (en) | 1988-02-29 | 1989-09-07 | Espe Stiftung | COMPATIBLE MATERIAL AND MATERIALS AVAILABLE THEREFROM |
GB2215209B (en) | 1988-03-14 | 1992-08-26 | Osmed Inc | Method and apparatus for biodegradable, osteogenic, bone graft substitute device |
JPH062154B2 (en) | 1988-03-30 | 1994-01-12 | 工業技術院長 | Powder for coating calcium phosphate-based substance, coating method and composite bioceramics |
US4880610A (en) | 1988-04-20 | 1989-11-14 | Norian Corporation | In situ calcium phosphate minerals--method and composition |
US5047031A (en) | 1988-04-20 | 1991-09-10 | Norian Corporation | In situ calcium phosphate minerals method |
US5053212A (en) | 1988-04-20 | 1991-10-01 | Norian Corporation | Intimate mixture of calcium and phosphate sources as precursor to hydroxyapatite |
US5129905A (en) | 1988-04-20 | 1992-07-14 | Norian Corporation | Methods for in situ prepared calcium phosphate minerals |
US4849193A (en) | 1988-05-02 | 1989-07-18 | United States Gypsum Company | Process of preparing hydroxylapatite |
JPH0773602B2 (en) | 1988-07-23 | 1995-08-09 | 新田ゼラチン株式会社 | Medical and dental curable materials |
US5573771A (en) | 1988-08-19 | 1996-11-12 | Osteomedical Limited | Medicinal bone mineral products |
JPH085712B2 (en) | 1988-09-15 | 1996-01-24 | 旭光学工業株式会社 | Oriented calcium phosphate compound moldings and sintered bodies, and methods for producing the same |
US5108436A (en) | 1988-09-29 | 1992-04-28 | Collagen Corporation | Implant fixation |
US5207710A (en) | 1988-09-29 | 1993-05-04 | Collagen Corporation | Method for improving implant fixation |
FR2646084B1 (en) | 1989-04-20 | 1994-09-16 | Fbfc International Sa | BIOREACTIVE MATERIAL FOR FILLING BONE CAVITES |
US5534244A (en) | 1989-05-24 | 1996-07-09 | Tung; Ming S. | Methods and compositions for mineralizing and/or fluoridating calcified tissues with amorphous strontium compounds |
US5324519A (en) | 1989-07-24 | 1994-06-28 | Atrix Laboratories, Inc. | Biodegradable polymer composition |
EP0417493A3 (en) | 1989-08-14 | 1991-04-03 | Aluminum Company Of America | Fiber reinforced composite having an aluminum phosphate bonded matrix |
US5236458A (en) | 1989-09-06 | 1993-08-17 | S.A. Fbfc International | Bioreactive material for a prosthesis or composite implants |
CA2027921C (en) | 1989-10-19 | 1997-12-09 | Nobuo Nakabayashi | Bone cement composition, cured product thereof, implant material and process for the preparation of the same |
US5112354A (en) | 1989-11-16 | 1992-05-12 | Northwestern University | Bone allograft material and method |
US5322675A (en) | 1990-11-09 | 1994-06-21 | Director-General Of Agency Of Industrial Science And Technology | Method of preparing calcium phosphate |
US5221558A (en) | 1990-01-12 | 1993-06-22 | Lanxide Technology Company, Lp | Method of making ceramic composite bodies |
US5290289A (en) | 1990-05-22 | 1994-03-01 | Sanders Albert E | Nitinol spinal instrumentation and method for surgically treating scoliosis |
US5129009A (en) * | 1990-06-04 | 1992-07-07 | Motorola, Inc. | Method for automatic semiconductor wafer inspection |
FR2664501B1 (en) | 1990-07-16 | 1995-05-12 | Osteal Medical Laboratoires | COMPOSITE MATERIAL FOR BONE IMPLANT AND METHOD FOR IMPLEMENTING SAME. |
GB2246770B (en) | 1990-07-27 | 1995-03-29 | Osaka Cement | Tetracalcium phosphate-based hardening materials |
DE4034786A1 (en) | 1990-11-02 | 1992-05-07 | Merck Patent Gmbh | METHOD AND DEVICE FOR THE PRODUCTION OF POWDER-SHAPED METAL OXIDES FOR CERAMIC MASSES |
EP0511868B1 (en) * | 1991-05-01 | 1996-09-25 | Chichibu Onoda Cement Corporation | Medical or dental hardening compositions |
US5306307A (en) | 1991-07-22 | 1994-04-26 | Calcitek, Inc. | Spinal disk implant |
US5338356A (en) | 1991-10-29 | 1994-08-16 | Mitsubishi Materials Corporation | Calcium phosphate granular cement and method for producing same |
US5170243A (en) | 1991-11-04 | 1992-12-08 | International Business Machines Corporation | Bit line configuration for semiconductor memory |
SE469653B (en) * | 1992-01-13 | 1993-08-16 | Lucocer Ab | POROEST IMPLANT |
US5211664A (en) | 1992-01-14 | 1993-05-18 | Forschungsinstitut, Davos Laboratorium Fur Experimentelle Chirugie | Shell structure for bone replacement |
DE69331096T2 (en) | 1992-02-28 | 2002-08-14 | Cohesion Tech Inc | INJECTABLE, CERAMIC COMPOUNDS AND METHOD FOR THE PRODUCTION AND USE THEREOF |
US5204382A (en) | 1992-02-28 | 1993-04-20 | Collagen Corporation | Injectable ceramic compositions and methods for their preparation and use |
US5320844A (en) | 1992-03-12 | 1994-06-14 | Liu Sung Tsuen | Composite materials for hard tissue replacement |
US5346492A (en) | 1992-03-30 | 1994-09-13 | Timesh, Inc. | Perforated metallic panels and strips for internal fixation of bone fractures and for reconstructive surgery |
US5302362A (en) | 1992-04-10 | 1994-04-12 | Uop | Crystalline microporous metallo-zinc phosphate compositions |
US5256292A (en) | 1992-04-16 | 1993-10-26 | Cagle William S | Screen for filtering undesirable particles from a liquid |
US5298205A (en) | 1992-05-11 | 1994-03-29 | Polyceramics, Inc. | Ceramic filter process |
JP2692026B2 (en) | 1992-09-08 | 1997-12-17 | 日本開発銀行 | Cellulose sponge made of non-wood material and method for producing the same |
JPH0798650B2 (en) | 1993-01-11 | 1995-10-25 | 工業技術院長 | Method for producing plate-shaped hydroxyapatite |
US5849813A (en) | 1993-02-05 | 1998-12-15 | Minnesota Mining And Manufacturing Company | Oxidative pretreatment for improved adhesion |
US5522893A (en) | 1993-03-12 | 1996-06-04 | American Dental Association Health Foundation | Calcium phosphate hydroxyapatite precursor and methods for making and using the same |
US5336642A (en) | 1993-09-01 | 1994-08-09 | Corning Incorporated | Canasite-apatite glass-ceramics |
US5531794A (en) * | 1993-09-13 | 1996-07-02 | Asahi Kogaku Kogyo Kabushiki Kaisha | Ceramic device providing an environment for the promotion and formation of new bone |
US5525148A (en) | 1993-09-24 | 1996-06-11 | American Dental Association Health Foundation | Self-setting calcium phosphate cements and methods for preparing and using them |
US5468544A (en) | 1993-11-15 | 1995-11-21 | The Trustees Of The University Of Pennsylvania | Composite materials using bone bioactive glass and ceramic fibers |
US5503164A (en) | 1994-01-28 | 1996-04-02 | Osteogenics, Inc. | Device and method for repair of craniomaxillofacial bone defects including burr holes |
US5626861A (en) | 1994-04-01 | 1997-05-06 | Massachusetts Institute Of Technology | Polymeric-hydroxyapatite bone composite |
US5591453A (en) | 1994-07-27 | 1997-01-07 | The Trustees Of The University Of Pennsylvania | Incorporation of biologically active molecules into bioactive glasses |
US5496399A (en) | 1994-08-23 | 1996-03-05 | Norian Corporation | Storage stable calcium phosphate cements |
US5707962A (en) | 1994-09-28 | 1998-01-13 | Gensci Regeneration Sciences Inc. | Compositions with enhanced osteogenic potential, method for making the same and therapeutic uses thereof |
US6180606B1 (en) | 1994-09-28 | 2001-01-30 | Gensci Orthobiologics, Inc. | Compositions with enhanced osteogenic potential, methods for making the same and uses thereof |
US7404967B2 (en) | 1994-12-21 | 2008-07-29 | Cosmederm, Inc. | Topical product formulations containing strontium for reducing skin irritation |
US5804203A (en) | 1994-12-21 | 1998-09-08 | Cosmederm Technologies | Topical product formulations containing strontium for reducing skin irritation |
US6139850A (en) | 1994-12-21 | 2000-10-31 | Cosmederm Technologies | Formulations and methods for reducing skin irritation |
US5716625A (en) | 1994-12-21 | 1998-02-10 | Cosmederm Technologies | Formulations and methods for reducing skin irritation |
US5573537A (en) | 1995-02-10 | 1996-11-12 | Rogozinski; Chaim | Instrument for probing and reaming a pedicle |
US6027742A (en) | 1995-05-19 | 2000-02-22 | Etex Corporation | Bioresorbable ceramic composites |
US5676976A (en) | 1995-05-19 | 1997-10-14 | Etex Corporation | Synthesis of reactive amorphous calcium phosphates |
US6287341B1 (en) | 1995-05-19 | 2001-09-11 | Etex Corporation | Orthopedic and dental ceramic implants |
US5984969A (en) | 1995-06-01 | 1999-11-16 | Johnson & Johnson Professional, Inc. | Joint prosthesis augmentation system |
US5702449A (en) * | 1995-06-07 | 1997-12-30 | Danek Medical, Inc. | Reinforced porous spinal implants |
US5660778A (en) | 1995-06-26 | 1997-08-26 | Corning Incorporated | Method of making a cross-flow honeycomb structure |
NZ315995A (en) | 1995-09-01 | 1999-09-29 | Millenium Biologix Inc | Artificial sintered composition comprising stabilised calcium phosphate phases capable of supporting bone cell activity |
US5984968A (en) | 1995-09-29 | 1999-11-16 | Park; Joon B. | Reinforcement for an orthopedic implant |
US5776193A (en) | 1995-10-16 | 1998-07-07 | Orquest, Inc. | Bone grafting matrix |
JPH09132406A (en) * | 1995-11-07 | 1997-05-20 | Mitsubishi Heavy Ind Ltd | Fine particles of phosphate of rare earth element and their production |
US5728753A (en) | 1995-11-09 | 1998-03-17 | University Of London | Bioactive composite material for repair of hard and soft tissues |
US6391286B1 (en) | 1995-11-17 | 2002-05-21 | 3M Innovative Properties Company | Use of metallofluorocomplexes for dental compositions |
CZ239598A3 (en) | 1996-01-29 | 1999-01-13 | University Of Maryland, Baltimore | Biologically active composition and treatment process in which the composition is employed |
US5782930A (en) | 1996-02-13 | 1998-07-21 | Hommedica Inc. | Polyetheretherketone (PEEK) retaining ring for an acetabular cup assembly |
EP0906128A1 (en) * | 1996-05-28 | 1999-04-07 | 1218122 Ontario Inc. | Resorbable implant biomaterial made of condensed calcium phosphate particles |
US6051247A (en) | 1996-05-30 | 2000-04-18 | University Of Florida Research Foundation, Inc. | Moldable bioactive compositions |
US5814682A (en) | 1996-06-14 | 1998-09-29 | Rusin; Richard P. | Method of luting a provisional prosthetic device using a glass ionomer cement system and kit therefor |
US6136885A (en) | 1996-06-14 | 2000-10-24 | 3M Innovative Proprerties Company | Glass ionomer cement |
US5824084A (en) | 1996-07-03 | 1998-10-20 | The Cleveland Clinic Foundation | Method of preparing a composite bone graft |
US6383159B1 (en) | 1998-11-10 | 2002-05-07 | Eunoe, Inc. | Devices and method for removing cerebrospinal fluids from a patient's CSF space |
US5834008A (en) | 1996-09-19 | 1998-11-10 | U.S. Biomaterials Corp. | Composition and method for acceleration of wound and burn healing |
US5914356A (en) | 1996-12-06 | 1999-06-22 | Orthovita, Inc. | Bioactive load bearing bone bonding compositions |
JP2001508436A (en) | 1997-01-13 | 2001-06-26 | デイビス・ショットランダー・アンド・デイビス・リミテッド | Improvements in or relating to the polymerizable cement composition |
US6013591A (en) * | 1997-01-16 | 2000-01-11 | Massachusetts Institute Of Technology | Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production |
FR2758988B1 (en) * | 1997-02-05 | 2000-01-21 | S H Ind | PROCESS FOR THE PREPARATION OF SYNTHETIC BONE SUBSTITUTES OF PERFECTLY MASTERED POROUS ARCHITECTURE |
US5977204A (en) | 1997-04-11 | 1999-11-02 | Osteobiologics, Inc. | Biodegradable implant material comprising bioactive ceramic |
US5928243A (en) | 1997-07-16 | 1999-07-27 | Spinal Concepts, Inc. | Pedicle probe and depth gage |
US6017346A (en) | 1997-07-18 | 2000-01-25 | Ultraortho, Inc. | Wedge for fastening tissue to bone |
US6281321B1 (en) | 1997-11-27 | 2001-08-28 | Akzo Nobel N.V. | Coating compositions |
US6019765A (en) | 1998-05-06 | 2000-02-01 | Johnson & Johnson Professional, Inc. | Morsellized bone allograft applicator device |
CN1293148C (en) | 1998-11-13 | 2007-01-03 | 三井化学株式会社 | Organic polymer/fine inorganic particle aqueous dispersion with excellent dispersion stability and use thereof |
US6328765B1 (en) | 1998-12-03 | 2001-12-11 | Gore Enterprise Holdings, Inc. | Methods and articles for regenerating living tissue |
US6383519B1 (en) * | 1999-01-26 | 2002-05-07 | Vita Special Purpose Corporation | Inorganic shaped bodies and methods for their production and use |
US6294187B1 (en) | 1999-02-23 | 2001-09-25 | Osteotech, Inc. | Load-bearing osteoimplant, method for its manufacture and method of repairing bone using same |
US6190643B1 (en) | 1999-03-02 | 2001-02-20 | Patricia Stoor | Method for reducing the viability of detrimental oral microorganisms in an individual, and for prevention and/or treatment of diseases caused by such microorganisms; and whitening and/or cleaning of an individual's teeth |
US6482427B2 (en) | 1999-04-23 | 2002-11-19 | Unicare Biomedical, Inc. | Compositions and methods for repair of osseous defects and accelerated wound healing |
US6288043B1 (en) | 1999-06-18 | 2001-09-11 | Orquest, Inc. | Injectable hyaluronate-sulfated polysaccharide conjugates |
US6458162B1 (en) * | 1999-08-13 | 2002-10-01 | Vita Special Purpose Corporation | Composite shaped bodies and methods for their production and use |
US6451059B1 (en) | 1999-11-12 | 2002-09-17 | Ethicon, Inc. | Viscous suspension spinning process for producing resorbable ceramic fibers and scaffolds |
US6593394B1 (en) | 2000-01-03 | 2003-07-15 | Prosperous Kingdom Limited | Bioactive and osteoporotic bone cement |
PT1250163E (en) | 2000-01-28 | 2005-04-29 | Dot Gmbh | INORGANIC REABSORVIVEL OSSEO REPLACEMENT MATERIAL AND PRODUCTION METHOD |
US6630153B2 (en) | 2001-02-23 | 2003-10-07 | Smith & Nephew, Inc. | Manufacture of bone graft substitutes |
US6372198B1 (en) | 2000-09-14 | 2002-04-16 | Joseph M. Abbate | Dentifrice for the mineralization and remineralization of teeth |
US7045125B2 (en) | 2000-10-24 | 2006-05-16 | Vita Special Purpose Corporation | Biologically active composites and methods for their production and use |
US20020193883A1 (en) | 2001-01-25 | 2002-12-19 | Wironen John F. | Injectable porous bone graft materials |
US6818682B2 (en) | 2001-04-20 | 2004-11-16 | 3M Innovative Properties Co | Multi-part dental compositions and kits |
NO20014746D0 (en) | 2001-09-28 | 2001-09-28 | Clas M Kjoelberg | Pain reliever |
US7173074B2 (en) | 2001-12-29 | 2007-02-06 | 3M Innovative Properties Company | Composition containing a polymerizable reducing agent, kit, and method |
US7514249B2 (en) | 2002-04-18 | 2009-04-07 | The University Of Florida Research Foundation, Inc. | Biomimetic organic/inorganic composites |
US7455854B2 (en) | 2002-04-18 | 2008-11-25 | University Of Florida Research Foundation, Inc. | Method for producing a mineral fiber |
AU2003228587A1 (en) | 2002-04-18 | 2003-11-03 | University Of Florida | Biomimetic organic/inorganic composites, processes for their production, and methods of use |
US7273523B2 (en) | 2002-06-07 | 2007-09-25 | Kyphon Inc. | Strontium-apatite-cement-preparations, cements formed therefrom, and uses thereof |
US7166133B2 (en) | 2002-06-13 | 2007-01-23 | Kensey Nash Corporation | Devices and methods for treating defects in the tissue of a living being |
US7189263B2 (en) | 2004-02-03 | 2007-03-13 | Vita Special Purpose Corporation | Biocompatible bone graft material |
GB0612028D0 (en) | 2006-06-16 | 2006-07-26 | Imp Innovations Ltd | Bioactive glass |
WO2008002682A2 (en) | 2006-06-29 | 2008-01-03 | Orthovita, Inc. | Bioactive bone graft substitute |
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 |
-
1999
- 1999-02-19 US US09/253,556 patent/US6383519B1/en not_active Expired - Lifetime
-
2000
- 2000-01-26 EP EP00904497A patent/EP1150659A4/en not_active Withdrawn
- 2000-01-26 AU AU26245/00A patent/AU767685B2/en not_active Ceased
- 2000-01-26 CA CA002359488A patent/CA2359488C/en not_active Expired - Fee Related
- 2000-01-26 MX MXPA01007552A patent/MXPA01007552A/en not_active IP Right Cessation
- 2000-01-26 IL IL14444800A patent/IL144448A0/en active IP Right Grant
- 2000-01-26 JP JP2000594448A patent/JP2002535225A/en active Pending
- 2000-01-26 WO PCT/US2000/001629 patent/WO2000042991A1/en active IP Right Grant
-
2001
- 2001-11-15 US US09/999,506 patent/US6521246B2/en not_active Expired - Lifetime
-
2002
- 2002-10-02 US US10/263,399 patent/US6991803B2/en not_active Expired - Lifetime
-
2003
- 2003-10-02 MX MXPA05003455A patent/MXPA05003455A/en active IP Right Grant
- 2003-10-02 AU AU2003277270A patent/AU2003277270B2/en not_active Ceased
- 2003-10-02 CA CA002500722A patent/CA2500722A1/en not_active Abandoned
- 2003-10-02 WO PCT/US2003/031370 patent/WO2004030655A1/en not_active Application Discontinuation
- 2003-10-02 EP EP03799403A patent/EP1545466B1/en not_active Revoked
-
2005
- 2005-05-24 US US11/136,317 patent/US20060039951A1/en not_active Abandoned
-
2010
- 2010-08-23 US US12/861,080 patent/US8303976B2/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5296261A (en) | 1991-07-01 | 1994-03-22 | Saft | Method of manufacturing a sponge-type support for an electrode in an electrochemical cell |
GB2260538A (en) | 1991-10-15 | 1993-04-21 | Peter Gant | Porous ceramics |
US5338334A (en) | 1992-01-16 | 1994-08-16 | Institute Of Gas Technology | Process for preparing submicron/nanosize ceramic powders from precursors incorporated within a polymeric foam |
US5681872A (en) * | 1995-12-07 | 1997-10-28 | Orthovita, Inc. | Bioactive load bearing bone graft compositions |
WO1998031630A1 (en) | 1997-01-16 | 1998-07-23 | Orthovita, Inc. | Novel minerals and methods for their production and use |
Non-Patent Citations (5)
Title |
---|
F. ABBONA; M. FRANCHINI-ANGELA; R. BOISTELLE: "Crystallization of calcium and magnesium phosphates from solutions of medium and low concentrations", CRYST. RES. TECHNOL., vol. 27, 1992, pages 41 |
G.H. NANCOLLAS: "The involvement of calcium phosphates in biological mineralization and demineralization processes", PURE APPL. CHEM., vol. 64, no. 11, 1992, pages 1673 |
G.H. NANCOLLAS; J. ZHANG: "Hydroxyapatite and Related Materials", 1994, CRC PRESS, INC., article "Formation and dissolution mechanisms of calcium phosphates in aqueous systems", pages: 73 - 81 |
S.J. POWELL; J.R.G. EVANS: "The structure of ceramic foams prepared from polyurethane-ceramic suspensions", MATERIALS & MANUFACTURING PROCESSES, vol. 10, no. 4, 1995, pages 757 |
See also references of EP1150659A4 |
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Also Published As
Publication number | Publication date |
---|---|
US20020140137A1 (en) | 2002-10-03 |
MXPA05003455A (en) | 2006-02-10 |
AU2003277270A1 (en) | 2004-04-23 |
CA2500722A1 (en) | 2004-04-15 |
AU2624500A (en) | 2000-08-07 |
CA2359488A1 (en) | 2000-07-27 |
US6991803B2 (en) | 2006-01-31 |
US20060039951A1 (en) | 2006-02-23 |
MXPA01007552A (en) | 2003-06-24 |
US20030175321A1 (en) | 2003-09-18 |
EP1545466B1 (en) | 2012-04-11 |
EP1545466A1 (en) | 2005-06-29 |
IL144448A0 (en) | 2002-05-23 |
EP1150659A1 (en) | 2001-11-07 |
AU767685B2 (en) | 2003-11-20 |
US8303976B2 (en) | 2012-11-06 |
EP1150659A4 (en) | 2005-03-30 |
WO2004030655A1 (en) | 2004-04-15 |
US20110014244A1 (en) | 2011-01-20 |
EP1545466A4 (en) | 2007-12-19 |
AU2003277270B2 (en) | 2009-05-07 |
US6521246B2 (en) | 2003-02-18 |
JP2002535225A (en) | 2002-10-22 |
US6383519B1 (en) | 2002-05-07 |
CA2359488C (en) | 2008-10-21 |
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