EP1727570A1 - Methods for preparing medical implants from calcium phosphate cement and medical implants - Google Patents
Methods for preparing medical implants from calcium phosphate cement and medical implantsInfo
- Publication number
- EP1727570A1 EP1727570A1 EP05723806A EP05723806A EP1727570A1 EP 1727570 A1 EP1727570 A1 EP 1727570A1 EP 05723806 A EP05723806 A EP 05723806A EP 05723806 A EP05723806 A EP 05723806A EP 1727570 A1 EP1727570 A1 EP 1727570A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- phosphate
- calcium
- calcium phosphate
- article
- hardened
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
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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
- 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
- A61F2/30—Joints
- A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
- A61F2/4644—Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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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
- C04B18/00—Use of agglomerated or waste materials or refuse as fillers for mortars, concrete or artificial stone; Treatment of agglomerated or waste materials or refuse, specially adapted to enhance their filling properties in mortars, concrete or artificial stone
- C04B18/02—Agglomerated materials, e.g. artificial aggregates
- C04B18/021—Agglomerated materials, e.g. artificial aggregates agglomerated by a mineral binder, e.g. cement
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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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- 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
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/30004—Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
- A61F2002/30011—Material related properties of the prosthesis or of a coating on the prosthesis the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis differing in porosity
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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
- A61F2002/30003—Material related properties of the prosthesis or of a coating on the prosthesis
- A61F2002/3006—Properties of materials and coating materials
- A61F2002/30062—(bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
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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
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
- A61F2002/30224—Three-dimensional shapes cylindrical
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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
- A61F2002/30108—Shapes
- A61F2002/30199—Three-dimensional shapes
- A61F2002/30224—Three-dimensional shapes cylindrical
- A61F2002/30235—Three-dimensional shapes cylindrical tubular, e.g. sleeves
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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
- A61F2/3094—Designing or manufacturing processes
- A61F2/30942—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques
- A61F2002/30957—Designing or manufacturing processes for designing or making customized prostheses, e.g. using templates, CT or NMR scans, finite-element analysis or CAD-CAM techniques using a positive or a negative model, e.g. moulds
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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
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0063—Three-dimensional shapes
- A61F2230/0069—Three-dimensional shapes cylindrical
-
- 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
- A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
- A61F2250/0023—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in porosity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00293—Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
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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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00353—Bone cement, e.g. polymethylmethacrylate or PMMA
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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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
- C04B2103/00—Function or property of ingredients for mortars, concrete or artificial stone
- C04B2103/0099—Aspecific ingredients, i.e. high number of alternative specific compounds mentioned for the same function or property
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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
Definitions
- TITLE METHODS FOR PREPARING MEDICAL IMPLANTS FROM CALCIUM PHOSPHATE CEMENT AND MEDICAL IMPLANTS
- the present invention is related to a medical implant made from calcium phosphate cement, and in particular to a method of preparing a molded and hardened calcium phosphate cement article having a superior compressive strength for use as medical implant.
- the molded and hardened calcium phosphate cement block may be in the forms of a dense block, a porous block for use as tissue-engineered scaffold, or a dual function block comprising a dense cortical portion bearing the majority of load and a porous cancellous portion allowing a rapid blood/body fluid penetration and tissue ingrowth.
- a prosthetic bone implant is bioresorbable and is supportive at the same time. Accordingly, an article made of calcium phosphate will be preferable than that made of a metal, if the former has strength which is comparable to a human cortical bone.
- One way of making such a bone implant is by sintering a calcium phosphate powder, particularly a hydroxyapatite (HA) powder, into a block material at a temperature generally greater than 1000°C.
- HA hydroxyapatite
- the conventional spinal fusing device is composed of a metallic cage and a bioresorbable material disposed in the metal cage, for example the one disclosed in US patent No. 5,645,598.
- An inevitable disadvantage of this fusion device is the sinking of the metallic cage sitting between two vertebrae to replace or repair a defect spinal disk, because the hardness and the relatively small size of the cage wear out or break the bone tissue, and in particular the endplate of the vertebra.
- a tissue-engineered scaffold (majority made from biodegradable polymers) has a very porous structure that allows living cells (usually taken from the patient being treated) to penetrate into the structure and be "seeded" in-vitro during a cell culture process.
- the cell-seeded scaffold is implanted into either an animal (e.g., rat) whose immune system has been removed, or into the patient himself (usually under the skin for easier later-on process).
- an animal e.g., rat
- the cells quickly multiply from absorbing nutrients from the animal or the patient's body, and, at the same time, the scaffold itself is gradually dissolved or resorbed.
- the implant now a real bone
- the implant is removed from under the skin of the animal or the patient and re-implanted into the (wounded or diseased) site being treated.
- tissue-engineered scaffold US 6,139,578; US 6,200,606; US 5,306,303; and US 6,132,463. It is advantageous if a tissue-engineered scaffold is bioresorbable, sufficiently porous and supportive at the same time.
- the conventional high temperature (usually >1000°C)-sintered porous hydroxyapatite (HA) block material does not possess sufficient micro/nano-sizied porosity and is hardly bioresorbable.
- the conventional biodegradable polymer for scaffold application exhibits a relatively low strength and too high a dissolution rate.
- An objective of the invention is to provide a molded and hardened calcium phosphate cement (CPC) article or block having a superior compressive strength for use as medical implant, which is free from the aforesaid drawbacks in the prior art.
- Another objective of the invention is to provide a porous hardened CPC article or block for use as a tissue-engineered scaffold, which is free from the aforesaid drawbacks in the prior art, or as a functional implant other than the tissue-engineered scaffold.
- Another objective of the invention is to provide a dual function hardened calcium phosphate cement (CPC) article or block for use as a prosthetic bone implant comprising a dense cortical portion and a porous cancellous portion, which is free from the aforesaid drawbacks in the prior art.
- the prosthetic bone implant constructed according to the present invention is made of a hardened calcium phosphate cement having an apatitic phase as a major phase, which comprises a dense cortical portion bearing the majority of load and a porous cancellous portion allowing a rapid bloodbody fluid penetration and tissue ingrowth.
- the prosthetic bone implant of the present invention is made by a novel technique, which involves immersing an article molded from two different pastes of calcium phosphate cement (CPC), one of them having an additional pore-forming powder, in a liquid for a period of time, so that the compressive strength of the molded CPC article is significantly improved after removing from the liquid while the pore-forming powder is dissolved in the liquid, creating pores in a desired zone or zones of the molded article.
- CPC calcium phosphate cement
- the dense cortical portion of the prosthetic bone implant made according to the present invention exhibits a high strength comparable to that of human cortical bone (about 110-170 MPa). The strength is adjustable by adjusting process parameters. 3.
- the dense cortical portion of the prosthetic bone implant made according to the present invention contains significant amount of micro- and nano-sized porosity, that improves bioresorbability thereof.
- the porous cancellous portion of the prosthetic bone implant made according to the present invention possesses a porosity greater than 40% in volume, prepferably 40-90%, allowing rapid blood/body fluid penetration and tissue ingrowth, thereby anchoring the prosthetic bone implant. 5.
- a wide range of medical application includes bone dowel, spacer, cavity filler, artificial disc and fixation devices for spine and other locations, to name a few.
- a novel method for making a hardened CPC article for use as medical implant involves impregnating an article molded from a paste of CPC in a liquid for a period of time, so that the compressive strength of the CPC block is significantly improved after removing from the liquid. It is apparent that the medical implant prepared according to this novel method has the features and advantages recited in the above-mentioned Items 3 and 5.
- a novel method for making a porous hardened CPC article for use as a tissue-engineered scaffold which involves preparing a shaped article from a paste comprising a calcium phosphate cement, a pore-forming powder and a setting liquid; and immersing said shaped article in an immersing liquid for a period of time so that said pore-forming powder is dissolved in the immersing liquid, creating pores in said shaped article.
- the porous hardened CPC article made according to the present invention has the following features and advantages: - The porous hardened CPC article can transform into an apatite-dominated material shortly after immersion in physiological solution or after implantation. - The porous hardened CPC article exhibits a higher strength than most other bioactive or biodegradable porous blocks with a similar porosity level.
- Figs. 2a to 2f are schematic cross sectional views showing steps of a method for preparing a prosthetic bone implant according to one embodiment of the present invention.
- Figs. 3a and 3b are schematic vertical and horizontal cross sectional views of a prosthetic bone implant prepared according to another embodiment of the present invention, respectively.
- the present invention discloses a method for making a hardened molded calcium phosphate cement (CPC) article comprising impregnating a rigid shaped article of calcium phosphate with an impregnating Hquid for a period of time so that a compressive strength of the resulting impregnated article removed from the impregnating liquid is increased compared to that of the rigid shaped article without said impregnating treatment.
- the impregnating liquid is an acidic solution, a basic solution, a physiological solution, an organic solvent, or a substantially pure water.
- the impregnating liquid comprises at least one of Ca and P sources.
- the impregnating liquid is a Hanks' solution, a HCl aqueous solution or an aqueous solution of(NH 4 ) 2 HP0 4 .
- the rigid shaped article of calcium phosphate is a molded article from a paste of calcium phosphate cement.
- the impregnating is carried out for a period longer than 10 minutes, and more preferably for about 12 hours to 96 hours.
- the impregnating is carried out 30-90°C, and more preferably at room temperature.
- a method for making a molded calcium phosphate article comprises the following steps: (a) preparing a powder of a calcium phosphate cement; (b) mixing said powder with a setting liquid to form a paste, wherein said paste undergoes a hardening reaction; (c) molding said paste into an article in a mold of a desired shape and size before said hardening reaction is complete; (d) impregnating the resulting hardened article from step (c) with an impregnating liquid to allow strength of said article to increase; and (e) removing said article from said impregnating liquid.
- said calcium phosphate cement comprises at least one Ca source and at least one P source, or more preferably at least one calcium phosphate source.
- Said calcium phosphate source comprises one or more calcium phosphates selected from the group consisting of alpha-tricalcium phosphate ( ⁇ -TCP), beta-tricalcium phosphate ( ⁇ -TCP), tetracalcium phosphate (TTCP), monocalcium phosphate monohydrate (MCPM), monocalcium phosphate anhydrous (MCPA), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate anhydrous (DCPA), octacalcium phosphate (OCP), calcium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, acid calcium pyrophosphate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate hydrate, calcium pyrophosphate, calcium triphosphate, calcium phosphate tribasic, calcium polyphosphate, calcium metaphosphate, anhydrous tricalcium phosphate, tricalcium phosphate, tri
- the calcium phosphate source comprises at least one calcium phosphate particle having calcium phosphate whiskers on the surface of said calcium phosphate particle, wherein said calcium phosphate whiskers have a length of about 1-5000 nm and a width of about 1-500 nm.
- the setting liquid in step (b) is an acidic solution, a basic solution, or a substantially pure water.
- An acidic solution suitable for use in the present invention is selected from the group consisting of nitric acid (HN0 3 ), hydrochloric acid (HCl), phosphoric acid (H 3 P0 ), carbonic acid (H 2 C0 3 ), sodium dihydrogen phosphate (NaH 2 P0 4 ), sodium dihydrogen phosphate monohydrate (NaH 2 P0 4 « H 2 0), sodium dihydrogen phosphate dihydrate, sodium dihydrogen phosphate dehydrate, potassium dihydrogen phosphate (KH 2 P0 4 ), ammonium dihydrogen.phosphate (NH H 2 P0 ), malic acid, acetic acid, lactic acid, citric acid, malonic acid, succinic acid, glutaric acid, tartaric acid, oxalic acid and their mixture.
- a basic solution suitable for use in the present invention is selected from the group consisting of ammonia, ammonium hydroxide, alkali metal hydroxide, alkali earth hydroxide, disodium hydrogen phosphate (Na 2 HP0 4 ), disodium hydrogen phosphate dodecahydrate, disodium hydrogen phosphate heptahydrate, sodium phosphate dodecahydrate (Na 3 P0 *12H 2 0), dipotassium hydrogen phosphate (K 2 HP0 ), potassium hydrogen phosphate trihydrate (K 2 HP0 4 »3H 2 0), potassium phosphate tribasic (K 3 PO 4 ), diammonium hydrogen phosphate ((NH ) 2 HP0 4 ), ammonium phosphate trihydrate ((NH 4 ) 3 P0 4 *3H 2 0), sodium hydrogen carbonate (NaHC0 3 ), sodium carbonate Na 2 C0 3 , and their mixture.
- Step (c) of the method of the present invention preferably further comprises removing said article from said mold.
- Step (c) of the method of the present invention preferably further comprises removing a portion of liquid from said paste, so that a liquid/powder ratio of said paste decreases.
- Step (c) of the method of the present invention preferably further comprises pressurizing said paste in said mold, preferably between 1 and 500 MPa, before said hardening reaction is complete to remove a portion of liquid from said paste, so that a liquid/powder ratio of said paste decreases. More preferably, step (c) further comprises heating said paste during said pressurizing.
- Step (c) of the method of the present invention preferably further comprises heating said paste during molding.
- Step (d) of the method of the present invention preferably further comprises heating the impregnating liquid, preferably at a temperature between 30 and 90°C during said impregnating.
- the method of the present invention may further comprise drying said article after removing said article from said impregnating liquid.
- the method of the present invention may further comprise heating said article, preferably at a temperature between 50 and 500°C, after removing said article from said impregnating liquid.
- the molded calcium phosphate article made according to the method of the present invention may be used as a medical implant or a reinforcing constituent of a composite. According to a second preferred embodiment of the present invention, a method for making a porous hardened CPC article is provided.
- the second preferred embodiment is similar to the first embodiment with a major difference in that a pore-forming powder is mixed with the powder of calcium phosphate cement used in step (a).
- the method for making a porous hardened CPC article according to the second preferred embodiment comprises: i) preparing a shaped article from a paste comprising a calcium phosphate cement, a pore-forming powder and a setting liquid; ii) immersing said shaped article in an immersing liquid for a first period of time so that said pore-forming powder is dissolved in the immersing liquid, creating pores in said shaped article; iii) removing the resulting porous shaped article from said immersing liquid; and iv) immersing the porous shaped article from step iii) in an impregnating liquid for a second period of time so that a compressive strength of the resulting article removed from the impregnating liquid is increased compared to that of said porous shaped article without said impregnating treatment, wherein step i
- Said pore-forming powder preferably is selected from the group consisting of LiCl, KC1, NaCl, MgCl 2 , CaCl 2 , NaI0 3 , KI, Na 3 P0 4 , K 3 P0 4 , Na 2 C0 3 , amino acid-sodium salt, amino acid-potassium salt, glucose, polysaccharide, fatty acid-sodium salt, fatty acid-potassium salt, potassium bitartrate (KHC 4 H 4 ⁇ 6 ), potassium carbonate, potassium gluconate (KC ⁇ H ⁇ 0 7 ), potassium-sodium tartrate (KNaC 4 H ⁇ 6 » 4H 2 ⁇ ), potassium sulfate (K 2 S0 4 ), sodium sulfate, and sodium lactate.
- said immersing liquid in step ii) and said impregnating liquid in step iv) independently are an acidic aqueous solution, a basic aqueous solution, a physiological solution, an organic solvent, or a substantially pure water.
- Said immersing liquid may comprises at least one of Ca and P sources.
- Said immersing liquid may be a Hanks' solution, a HCl aqueous solution or an aqueous solution of (NH 4 ) 2 HP0 4 .
- Said impregnating liquid in step iv) may be different from or the same as the immersing liquid in step i).
- the first period of time in step ii) is longer than 10 minutes, and more preferably longer than 1 day.
- the second period of time in step iv) is longer than 10 minutes, and more preferably longer than 1 day.
- the immersing in step ii) and iv) is carried out at room temperature or at a temperature between about 30 and 90°C.
- said paste in step i) further comprises living cells.
- said immersing liquid in step ii) comprises living cells.
- said impregnating liquid in step iv) comprises living cells.
- said porous shaped article having an increased compressive strength removed from said impregnating liquid in step iv) has a porosity of at least 20 vol%, and more preferably of 40-90 vol%.
- the porous hardened CPC article made according to the method of the present invention may be used as a tissue-engineered scaffold, medical implant or a reinforcing constituent of a composite.
- a method for making a dual function hardened CPC article for use as a prosthetic bone implant is provided.
- the third preferred embodiment basically is a combination of the first embodiment and the second embodiment, wherein a first CPC paste without the pore-forming powder and a second CPC paste containing the pore-forming powder are used to mold an integral article and immersing the integral article in the impregnating liquid, so that the pore-forming powder is dissolved in the immersing liquid, creating pores in the integral article while the hardened CPC gaining compressive strength.
- Features of the third preferred embodiments of the present invention includes (but not limited to) the following:
- a prosthetic bone implant comprising a cortical portion having two opposite sides, and a cancellous portion integrally disposed in said cortical portion and being exposed through said two opposite sides, wherein said cortical portion comprises a hardened calcium phosphate cement has a porosity of less than 40% in volume, and said cancellous portion comprises a porous hardened calcium phosphate cement having a porosity greater than 20% in volume, and greater than that of said cortical portion.
- the prosthetic bone implant according to Feature 2 further comprising a transitional portion between said column and said hollow disk surrounding said central cylinder, which has properties range from those of said cancellous portion to said cortical portion.
- the prosthetic bone implant according to Feature 1 wherein the cortical portion is in the form of a disk having one or more longitudinal through holes, and the cancellous portion is in the form of one or more columns surrounded by said one or more longitudinal through holes.
- said hardened calcium phosphate cement of said cortical portion comprises an apatitic phase as a major phase giving rise to broadened characteristic X-ray diffraction peaks in comparison with a high-temperature sintered apatitic phase.
- said broadened characteristic the X-ray diffraction peaks are at 2-Theta values of 25-27° and 30-35°.
- 7. The prosthetic bone implant according to Feature 1 wherein said hardened calcium phosphate cement of said cortical portion is prepared without a high temperature sintering.
- a method for preparing a prosthetic bone implant comprising a cortical portion having two opposite sides, and a cancellous portion integrally disposed in said cortical portion and being exposed through said two opposite sides, said method comprises the following steps: a) preparing a first paste comprising a first calcium phosphate cement and a first setting liquid; b) preparing a second paste comprising a second calcium phosphate cement, a pore-forming powder and a second setting liquid; c) i) preparing a shaped article in a mold having two or more cells separated by one more partition walls comprising introducing said first paste and said second paste into said two or more cells separately, and removing said one or more partition walls from said mold, so that said second paste in the form of a single column or two or more isolated columns is integrally disposed in the first paste in said mold; or ii) preparing a shaped article comprising introducing one of said first paste and said second paste into a first mold to form an intermediate in said first mold, placing said intermediate into a
- said first calcium phosphate cement comprises at least one Ca source and at least one P source, or at least one calcium phosphate source; and said second calcium phosphate cement comprises at least one Ca source and at least one P source, or at least one calcium phosphate source.
- first setting liquid and the second setting liquid independently are an acidic solution, a basic solution, or a substantially pure water.
- step c-i) further comprises allowing said first paste and said second paste undergoing a hardening reaction in said mold.
- step c-i) further comprises pressurizing said first paste and said second paste in said mold after removing said one or more partition walls from said mold to remove a portion of liquid from said first paste and said second paste, so that a liquid/powder ratio of said first paste and of said second paste decreases; and allowing said first paste and second paste undergoing a hardening reaction in said mold.
- step c-ii) further comprises allowing said intermediate undergoing a hardening reaction in said first mold, and allowing said another one of said first paste and said second paste undergoing a hardening reaction in said second mold.
- step c-ii) further comprises pressurizing said one of said first paste and said second paste in said first mold to remove a portion of liquid therefrom before the hardening reaction of said intermediate is completed; allowing said intermediate undergoing a hardening reaction in said first mold; pressuring said another one of said first paste and said second paste in said second mold, so that a liquid/powder ratio of said another one of said first paste and of said second paste decreases; and allowing said another one of said first paste and second paste undergoing a hardening reaction in said second mold.
- the immersing liquid is an acidic aqueous solution, a basic aqueous solution, a physiological solution, an organic solvent, or a substantially pure water.
- step d) The method according to Feature 16, wherein the immersing in step d) is carried out for a period longer than 10 minutes.
- Figs, la to Id Four different designs of prosthetic bone implants constructed according to the present invention are shown in Figs, la to Id.
- the prosthetic bone implant of the present invention has a dense cortical portion Dl in the tubular form and a porous cancellous portion PI formed in the central through hole of the tubular cortical portion Dl.
- Both the dense cortical portion Dl and the porous cancellous portion PI are made of a hardened calcium phosphate cement having an apatitic phase as a major phase.
- Fig. la the dense cortical portion Dl in the tubular form and a porous cancellous portion PI formed in the central through hole of the tubular cortical portion Dl.
- Both the dense cortical portion Dl and the porous cancellous portion PI are made of a hardened calcium phosphate cement having an apatitic phase as a major phase.
- the prosthetic bone implant of the present invention has a dense cortical portion Dl in the tubular form; a cylindrical porous cancellous portion P 1 in the center of the tubular cortical portion D 1 ; and an annular transitional portion P2 connecting the tubular cortical portion D 1 and the cylindrical cancellous portion P 1.
- the transitional portion P2 is made of a hardened calcium phosphate cement having an apatitic phase as a major phase, and a porosity gradient increasing from the lower porosity of the cylindrical cancellous portion P 1 to the higher porosity of the tubular cortical portion Dl, which may be formed in-situ during molding of two different two different CPC pastes, one of them having an additional pore-forming powder for forming the cylindrical cancellous portion P 1 , and another one being a regular CPC powder for forming the dense cortical portion D 1.
- the porous cancellous portion P 1 may be in the forms of isolated columns surrounded by the dense cortical portion Dl as shown in Figs, lc and Id.
- a suitable method for preparing the prosthetic bone implant of the present invention includes placing a tubular partition wall 10 in a hollow cylindrical mold 20, as shown in Fig. 2a; pouring a first paste comprising a calcium phosphate cement and a setting liquid in the annular cell and a second paste comprising the calcium phosphate cement, a pore-forming powder and the setting liquid in the central cell, as shown in Fig. 2b; removing the partition wall and pressing the CPC pastes before hardening, as shown in Fig. 2c, wherein a portion of the setting liquid is removed from the gap between the mold 20 and the press 30 and/or holes (not shown in the drawing) provided on the press 30.
- the CPC paste will undergo a hardening reaction to convert into apatitic phase.
- the hardened disk is removed from the mold and is subjected to surface finishing to expose the central portion hardened from the second paste, as shown in Fig. 2d, followed by immersing in a bath of an immersing liquid as shown in Fig. 2e, where the pore-forming powder is dissolved in the immersing liquid while the hardened CPC thereof gaining compressive strength.
- the immersing may last from 10 minutes to several days.
- the composite disk so formed is washed with water after being removed from the bath, and dried and heated in an oven to obtain the prosthetic bone implant as shown in Fig. 2f.
- An alternative method for preparing the prosthetic bone implant of the present invention from the same raw materials includes pouring the second paste in a first mold, pressing the second paste to remove a portion of the setting liquid from the second paste before the hardening reaction is completed, so that the liquid/powder ratio in the second paste decreases, and allowing the hardening reaction undergo in the mold for a period of time, e.g. 15 minutes starting from the mixing of the CPC powder, the pore-forming powder and the setting liquid, to obtain a cylindrical block having a diameter of 7 mm.
- the cylindrical block is removed from the first mold, and placed in the center of a second mold having a diameter of 10 mm.
- the first paste is poured into the annular space in the second mold, and a press having a dimension corresponding to the annular shape is used to pressure the first paste to remove a portion of the setting liquid from the first paste before the hardening reaction is completed, so that the liquid/powder ratio in the first paste decreases.
- the first paste will undergo a hardening reaction to convert into apatitic phase.
- the hardened cylinder having a diameter of 10 mm is removed from the second mold, followed by immersing in an immersing liquid, where the pore-forming powder contained in the second paste is dissolved in the immersing liquid while the hardened CPC thereof gaining compressive strength, to obtain the prosthetic bone implant of the present invention, as shown in Figs. 3a and 3b.
- the prosthetic bone implant shown in Figs. 3 a and 3b can also be prepared by changing the sequence of the molding of the first paste and the second paste with modifications to the second mold used in this alternative method.
- the following examples are intended to demonstrate the invention more fully without acting as a limitation upon its scope, since numerous modifications and variations will be apparent to those skilled in this art.
- TTCP powder A Ca 4 (P0 4 ) 2 0 (TTCP) powder was prepared by mixing Ca 2 P 2 0 7 powder with CaC0 3 powder uniformly in ethanol for 24 hours followed by heating to dry. The mixing ratio of Ca 2 P 2 0 7 powder to CaC0 3 powder was 1 : 1.27 (weight ratio) and the powder mixture was heated to 1400°C to allow two powders to react to form TTCP.
- EXAMPLE 2 Preparation of conventional TTCP/DCPA-based CPC powder (abbreviated as C-CPC) The resulting TTCP powder from PREPARATIVE EXAMPLE 1 was sieved and blended with dried
- CaHP0 4 (DCPA) powder in a ball mill for 12 hours.
- the blending ratio of the TTCP powder to the DCPA powder was 1 : 1 (molar ratio) to obtain the conventional CPC powder. Particles of this C-CPC powder have no whisker on the surfaces thereof.
- PREPARATIVE EXAMPLE 3 Preparation of non-dispersive TTCP/DCPA-based CPC powder (abbreviated as ND-CPC)
- the TTCP powder prepared according to the method of PREPARATIVE EXAMPLE 1 was sieved and blended with dried CaHP0 4 (DCPA) powder in a ball mill for 12 hours.
- the blending ratio of the TTCP powder to the DCPA powder was 1 : 1 (molar ratio).
- the resultant powder mixture was added to a 25 mM diluted solution of phosphate to obtain a powder/solution mixture having a concentration of 3 g powder mixture per 1 ml solution while stirring.
- the resulting powder/solution mixture was formed into pellets, and the pellets were heated in an oven at 50°C for 10 minutes.
- the pellets were then uniformly ground in a mechanical mill for 20 minutes to obtain the non-dispersive TTCP/DCPA-based CPC powder (ND-CPC).
- the particles of this ND-CPC powder have
- EXAMPLE 1 Effect of immersion time on compressive strength of CPC block
- the ND-CPC powder from PREPARATIVE EXAMPLE 3 was added in a liquid/powder ratio (L/P ratio) of 0.4, i.e. 4 ml liquid/10 g powder, while stirring.
- the resulting paste was filled into a cylindrical steel mold having a length of 12 mm and a diameter of 6 mm, and was compressed with a gradually increased pressure until a maximum pressure was reached. The maximum pressure was maintained for one minute, and then the compressed CPC block was removed from the mold.
- the compressed CPC block was immersed in a Hanks' solution for 1 day, 4 days, and 16 days.
- Each test group of the three different periods of immersion time has five specimens, the compressive strength of which was measured by using a AGS-500D mechanical tester (Shimadzu Co., Ltd., Kyoto, Japan) immediately following the removal thereof from the Hanks' solution without drying.
- the CPC paste in the mold was compressed with a maximum pressure of 166.6 MPa, and in the course of the compression the compression speeds were about 5 mm/min during 0-104.1 MPa; 3 mm/min during 104.1-138.8 MPa; 1 mm/min during 138.8-159.6 MPa: and 0.5 mm/min during 159.6-166.6 MPa.
- the measured wet specimen compressive strength is listed Table 1.
- EXAMPLE 2 Effect of whiskers on compressive strength of TTCP/DCPA-based CPC block The procedures of EXAMPLE 1 were repeated by using the C-CPC powder prepared in PREPARATIVE EXAMPLE 2 and the ND-CPC powder prepared in PREPARATIVE EXAMPLE 3. The maximum pressure used to compress the CPC paste in the mold in this example was 156.2 MPa. The results for one-day immersion time are listed in Table 2.
- EXAMPLE 3 Effect of whiskers on compressive strength of TTCP-based CPC block Ca 4 (P0 4 ) 2 0 (TTCP) powder as synthesized in PREPARATIVE EXAMPLE 1 was sieved with a #325 mesh.
- the sieved powder has an average particle size of about 10 ⁇ m.
- the TTCP powder was immersed in the HCl aqueous solution for 12 hours, filtered rapidly and washed with deionized > water, and filtered rapidly with a vacuum pump again.
- the resulting powder cake was dried in an oven at 50°C.
- the dried powder was divided into halves, ground for 20 minutes and 120 minutes separately, and combined to obtain the non-dispersive TTCP-based CPC powder, the particles of which have whisker on the surfaces thereof.
- a setting solution of diammonium hydrogen phosphate was prepared by dissolving 20 g of diammonium hydrogen phosphate, (NH4)2HP ⁇ 4, in 40 ml deionized water.
- the procedures in EXAMPLE 1 were used to obtain the wet specimen compressive strength for one-day immersion time, wherein the maximum pressure to compress the CPC paste in the mold was 156.2 MPa. The results are shown in Table 3.
- Table 3 Table 3
- EXAMPLE 4 Effect of molding pressure on compressive strength of ND-CPC block (in low pressure regime: 0.09-3.5 MPa) The procedures of EXAMPLE 1 were repeated except that the maximum pressure used to compress the CPC paste in the mold was changed from 166.6 MPa to the values listed in Table 4. The period of immersion was one day. The results are listed in Table 4. Table 4
- EXAMPLE 5 Effect of reducing liquid/powder ratio during compression of the CPC paste in the mold on compressive strength of ND-CPC block The procedures of EXAMPLE 1 were repeated except that the maximum pressure used to compress the
- EXAMPLE 6 Effect of post-heat treatment on compressive strength of CPC block The procedures of EXAMPLE 1 were repeated. The period of immersion was one day. The CPC blocks after removing from the Hanks' solution were subjected to post-heat treatments: 1) 50°C for one day; and 2) 400°C for two hours with a heating rate of 10°C per minute. The results are listed in Table 6.
- EXAMPLE 7 Effect of KCl content and immersion time on compressive strength of porous CPC block
- the ND-CPC powder from PREPARATIVE EXAMPLE 3 was added in a liquid/powder ratio (L/P ratio) of 0.4, i.e. 4 ml liquid/10 g powder, while stirring.
- KCl powder in a predetermined amount was mixed to the resulting mixture by stirring intensively.
- the resulting paste was filled into a cylindrical steel mold having a length of 12 mm and a diameter of 6 mm, and was compressed with a gradually increased pressure until a maximum pressure of 3.5 MPa was reached.
- EXAMPLE 8 Porosity and compressive strength of porous CPC blocks prepared from different pore-forming powders The procedures of EXAMPLE 7 were repeated by using sugar, KI, C 17 H 33 COONa and C ⁇ 3 H 27 COOH instead of KCl. The immersion time was 14 days in deionized water. In the cases where the C ⁇ 7 H 33 COONa and C 13 H 27 COOH were used, the CPC blocks were further immersed in ethanol for additional four days. The conditions and the results are listed in Table 8.
- a S Pore-forming powder/CPC by volume.
- C.S. dry compressive strength (hereinafter abbreviated as C.S.).
- Porosity Porosity (vol%) was measured by Archimedes' method, and calculated as in ASTM C830.
- L/P ratio liquid/powder ratio
- the CPC/KCl composite block was immersed in a deionized water at 37°C for 4 days. KCl powder was dissolved in the deionized water, and a dual-functional CPC block having a porous CPC cylinder surround by a dense CPC annular block was obtained. The compressive strength of the specimen was measured by using a AGS-500D mechanical tester
Abstract
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US10/780,728 US7163651B2 (en) | 2004-02-19 | 2004-02-19 | Method for making a porous calcium phosphate article |
US10/852,167 US6994726B2 (en) | 2004-05-25 | 2004-05-25 | Dual function prosthetic bone implant and method for preparing the same |
PCT/US2005/006100 WO2005079880A1 (en) | 2004-02-19 | 2005-02-22 | Methods for preparing medical implants from calcium phosphate cement and medical implants |
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CN110563395A (en) * | 2019-09-16 | 2019-12-13 | 安阳师范学院 | light high-hardness civil engineering material and preparation method thereof |
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WO2007044229A2 (en) * | 2005-09-28 | 2007-04-19 | Calcitec, Inc. | Surface treatments for calcium phosphate-based implants |
US8388626B2 (en) * | 2006-11-08 | 2013-03-05 | Warsaw Orthopedic, Inc. | Methods of employing calcium phosphate cement compositions and osteoinductive proteins to effect vertebrae interbody fusion absent an interbody device |
FR2938423B1 (en) * | 2008-11-18 | 2012-01-13 | Kasios | IMPLANT FOR PROMOTING THE BONE PUSH OF THE MAXILLARY BONE AND KIT COMPRISING AN IMPLANT OF THIS TYPE |
KR101413541B1 (en) * | 2012-11-30 | 2014-07-02 | 안동대학교 산학협력단 | Method for manufacturing a three-dimensional scaffold |
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JPS63125259A (en) * | 1986-11-14 | 1988-05-28 | 旭光学工業株式会社 | Calcium phosphate type porous bone filler |
US6149688A (en) * | 1995-06-07 | 2000-11-21 | Surgical Dynamics, Inc. | Artificial bone graft implant |
TWI291352B (en) * | 2000-07-13 | 2007-12-21 | Calcitec Inc | Calcium phosphate cement, use and preparation thereof |
US6955716B2 (en) * | 2002-03-01 | 2005-10-18 | American Dental Association Foundation | Self-hardening calcium phosphate materials with high resistance to fracture, controlled strength histories and tailored macropore formation rates |
TWI275386B (en) * | 2003-08-05 | 2007-03-11 | Cana Lab Corp | Methods for preparing medical implants from calcium phosphate cement and medical implants |
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