WO2009148553A2 - Bioceramic and biopolymer composite - Google Patents
Bioceramic and biopolymer composite Download PDFInfo
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- WO2009148553A2 WO2009148553A2 PCT/US2009/003307 US2009003307W WO2009148553A2 WO 2009148553 A2 WO2009148553 A2 WO 2009148553A2 US 2009003307 W US2009003307 W US 2009003307W WO 2009148553 A2 WO2009148553 A2 WO 2009148553A2
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- bioceramic
- calcium phosphate
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- precursor mixture
- biopolymer
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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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
- A61K6/864—Phosphate cements
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
- A61K6/876—Calcium oxide
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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
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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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
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/327—After-treatment
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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
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/01—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics
- C04B35/447—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products based on oxide ceramics based on phosphates, e.g. hydroxyapatite
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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
- C04B38/04—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by dissolving-out added substances
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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
- C04B38/06—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by burning-out added substances by burning natural expanding materials or by sublimating or melting out added substances
- C04B38/063—Preparing or treating the raw materials individually or as batches
- C04B38/0635—Compounding ingredients
- C04B38/0645—Burnable, meltable, sublimable materials
- C04B38/068—Carbonaceous materials, e.g. coal, carbon, graphite, hydrocarbons
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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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- 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
- C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
- C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
- C04B2235/30—Constituents and secondary phases not being of a fibrous nature
- C04B2235/32—Metal oxides, mixed metal oxides, or oxide-forming salts thereof, e.g. carbonates, nitrates, (oxy)hydroxides, chlorides
- C04B2235/3205—Alkaline earth oxides or oxide forming salts thereof, e.g. beryllium oxide
- C04B2235/3208—Calcium oxide or oxide-forming salts thereof, e.g. lime
- C04B2235/3212—Calcium phosphates, e.g. hydroxyapatite
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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
- C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
- C04B2235/02—Composition of constituents of the starting material or of secondary phases of the final product
- C04B2235/30—Constituents and secondary phases not being of a fibrous nature
- C04B2235/34—Non-metal oxides, non-metal mixed oxides, or salts thereof that form the non-metal oxides upon heating, e.g. carbonates, nitrates, (oxy)hydroxides, chlorides
- C04B2235/3418—Silicon oxide, silicic acids, or oxide forming salts thereof, e.g. silica sol, fused silica, silica fume, cristobalite, quartz or flint
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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
- C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
- C04B2235/60—Aspects relating to the preparation, properties or mechanical treatment of green bodies or pre-forms
- C04B2235/604—Pressing at temperatures other than sintering temperatures
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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
- C04B2235/00—Aspects relating to ceramic starting mixtures or sintered ceramic products
- C04B2235/70—Aspects relating to sintered or melt-casted ceramic products
- C04B2235/96—Properties of ceramic products, e.g. mechanical properties such as strength, toughness, wear resistance
Definitions
- the present invention relates generally to bioceramic implants and methods of manufacturing the same for use, either alone or in combination with pharmaceutical agents, as bone substitutes in the fields of orthopedics and dentistry.
- Orthopedic reconstruction procedures routinely involve the surgical introduction of structural implants that provide for skeletal function, rigid fixation and bone integration.
- implantable devices may require a degree of geometry adjustment to accommodate the specific constraints of an implant site. Consequently, there are clinical advantages for a high performance bone substitute to be able to withstand shaping, drilling and threading, without fragmentation.
- biopolymers into bioceramics has the potential to combine the strength, stiffness and osteoconductivity of calcium-based bioceramics with the toughness and controlled biodegradability of a polymeric phase.
- Methods of fabrication typically involve the infusion of the biopolymer into the interstitial spaces within a bioceramic network, such as the method described in US 2004/004305 IAl.
- Biodegradable polymers have been used as drug delivery vehicles as they can be implanted directly at the site of repair and their rate of degradation and, hence, rate of drug delivery can be controlled.
- biodegradable polymers do not possess the mechanical properties suitable for hard tissue replacement.
- there has been an increased interest in polymeric/ceramic composites as disclosed for example U.S. 5,766,618 and International Pat. No. WO 99/19003.
- bioceramic and biopolymer composite that has the required biological and mechanical properties to allow successful performance in high load areas of the skeleton.
- Such composites should allow for the shaping, drilling and threading of the implant to enable a wide range of implant customization techniques during operative placement and fixation.
- the biopolymer phase would enable the progressive release of pharmaceutical agents to stimulate and accelerate biological processes underway at the implant site.
- a high performance porous bioceramic that has enhanced tensile and compressive strength due to the ability to compression form the bioceramic precursor and a pore forming agent under high load prior to sintering. Methods of making and using the same are also provided.
- a bioceramic that has high strength due to the ability to compression form a bioceramic under high load prior to sintering and bioceramic composite wherein pores in the bioceramic have been filed with a biopolymer and/or a therapeutic.
- a porous bioceramic that has high strength due to compression forming the bioceramic under high load in combination with a porogen prior to sintering, wherein sintering removes the porogen leaving a porous high strength bioceramic, which may optionally have the pores filed with a biopolymer and/or therapeutic agent.
- the porogen substantially retains it's volume during compression forming, such that the porogen does not shrink in response to compression forming, only to expand following release of the compression forming forces and crack the green (i.e. non-sintered) body.
- a spongy material or compressible material such as Styrofoam, are not suitable porogens for the present invention.
- Such porogens simply collapse under the pressure of compression forming and result in only interconnected microscopic pores, whereas the pores of the present invention are both microscopic and macroscopic.
- the macroscopic pores are in the ranges of, for example, about 10 to about 500 ⁇ m, about 50 to about 400 ⁇ m, about 100 to about 350 ⁇ m, or about 150 to about 300 ⁇ m, in diameter.
- porogens that compress significantly under the forming pressure, but expand upon release of the pressure are unsuitable for the present invention, as the post-forming expansion of the included porogen would crack or fracture the green body.
- porogens that do not crack the green body upon release from the compression forming process, but subsequently expand in the subsequent sintering process and damage the compression molded part are unsuitable for the present invention.
- gas forming compounds are not suitable porogens, as the formation of gas is not practical under a compression molding process.
- Exemplary porogens include, but are not limited to, organic particles (e.g., corn or potato starch, wood dust or wood pulp, sugar, ground coffee beans or other ground plant mater, etc.), carbon-based particles (e.g., charcoal, coke, graphite, etc. ), petroleum-based particles (e.g., carbon black, paraffin, etc.) and salts (e.g. sodium chloride, magnesium chloride, etc.).
- organic particles e.g., corn or potato starch, wood dust or wood pulp, sugar, ground coffee beans or other ground plant mater, etc.
- carbon-based particles e.g., charcoal, coke, graphite, etc.
- petroleum-based particles e.g., carbon black, paraffin, etc.
- salts e.g. sodium chloride, magnesium chloride, etc.
- the invention provides a bioceramic and/or bioceramic composite having a compression strength of at least about 10 MegaPascal (MPa), at least about 20 MPa, between about 10 and about 100 MPa, between about 20 and about 100 MPa, or between about 20 and about 90 MPa.
- MPa MegaPascal
- a high performance bioceramic and biopolymer composite that enables the post- implantation release of pharmaceutical compounds contained in the biopolymer phase.
- a method for producing a porous bioceramic comprising compacting a bioceramic precursor in combination with a compression resistant porogen, sintering the bioceramic/porogen mixture and removing the porogen by either subsequently dissolving the porogen from within the bioceramic or by pyrolysis of the porogen during sintering, wherein the resulting bioceramic may optionally have the pores filled by infusing the bioceramic with a biopolymer and/or a therapeutic agent.
- a method for producing a bioceramic composite comprising mixing a porogen and a bioceramic precursor composition, placing the porogen/bioceramic mixture in a mold, compacting the porogen/bioceramic mixture, releasing the composite from the mold, sintering the bioceramic and optionally infusing the bioceramic with a biopolymer and/or a therapeutic agent.
- a method for producing a bioceramic composite comprising mixing a porogen and a bioceramic precursor composition, placing the porogen/bioceramic mixture in a mold, compacting porogen/bioceramic mixture, sintering the bioceramic, and releasing the composite from the mold and optionally infusing the bioceramic with a biopolymer and/or a therapeutic agent.
- Exemplary therapeutic agents include, but are not limited to, members of the BMP protein family, such as osteogenically active forms of OP-I, OP-2, OP-3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-9, BMP-IO, BMP-I l, BMP-13, BMP- 15, GDF-I, GDF-3, GDF-5, GDF-6, GDF-7, and amino acid sequence variants thereof, analgesics and/or antibiotics. See U.S. Patent Pubs. 2008/0014250 and 2009/0048412.
- a significant improvement provided by the invention is the production of a synthetic bone replacement/regeneration ceramic that possess the clinically required mechanical properties for high load applications, while maintaining the ability to be fully remodeled by the body.
- a high performance bioceramic and biopolymer composite bone substitute, a method of its manufacture and use are provided herein.
- the bioceramic which may optionally include a biopolymer and/or therapeutic agent, addresses the limitations of prior techniques to form high performance and/or highly compression resistant implants that retain the benefits of pore formation without a substantial sacrifice in performance and/or compression resistance.
- the technique involves the initial preparation of a fully sintered bioceramic body prepared with a controlled concentration of interconnected pores that may be subsequently infiltrated with a polymeric species and/or a therapeutic agent.
- bioceramic and bioceramic composites can be formed based on the use of high compression molding of the bioceramic in the green state, and optionally the resulting pores may subsequently be substantially filled by biopolymer infusion.
- certain pore forming agents i.e., porogens
- porogens have been identified that can withstand the high compaction presure (e.g. between about 30MPa and about 60MPa) incurred during forming in the green state and that my be subsequently removed from the compacted bioceramic through high temperature sintering to produce a porous structure of high mechanical strength.
- the subsequent infiltration of the porous bioceramic with a biopolymer produces an implantable device having a mechanical strength sufficient to withstand customization through shaping, drilling and/or threading.
- a biopolymer may be used as a drug delivery aid for the release of pharmaceutical compounds at the implant site.
- the composite may be tailored by varying a) the composition of the bioceramic precursor; b) the composition and/or particle size and/or relative quantity of the porogen; c) the selection of the biopolymer relative to another; and/or d) by the quantity of the porogen added.
- the bioceramic may be primarily hydroxyapatite, tricalcium phosphate, magnesium stabilized calcium phosphate, silicon substituted calcium phosphate or mixtures thereof.
- the greater the porogen content in the milled powder generally the higher the level of porosity observed in the sintered ceramic and the higher the fraction of biopolymer that can be incorporated in the final composite.
- Composites prepared with the inclusion of 0-80 wt% graphite have been successfully prepared and have allowed for the fabrication of composites having a composition ratio of 95/5 to 65/35, bioceramic to biopolymer.
- the porogen is at least partially removed, and in certain examples at least substantially removed, to produce a porous bioceramic structure, which may optionally be infused with a biopolymer and/or therapeutic agent.
- the porogen may be removed by any suitable method, for example by leaching the porogen in solution or by pyrolysis during sintering of the bioceramic structure.
- a high performance bioceramic bone substitute, optionally carrying a biopolymer, and method of making and method of use thereof may overcome one or more of the disadvantages of the prior art and provides one or more of the following advantages:
- Pore formation occurs through the use of porogens that withstand the high compressive loads incurred during green body compaction;
- Pore formation in the bioceramic structure occurs through the high temperature sintering of the bioceramic structure - no additional processing steps are required;
- the biopolymer may be selected for structural advantages or for the ability to provide controlled release of pharmaceuticals (e.g. BMP) that influence tissue repair and regeneration;
- pharmaceuticals e.g. BMP
- the combination of the porous bioceramic and the infiltrated biopolymer enables the bioceramic composite to be readily handled and shaped, for example, by the surgeon, using standard techniques; and/or
- the bioceramic or composite may be secured into place using standard orthopedic fixation techniques, such as screws threaded through predrilled holes in the implant, without structural damage or the generation of particulate debris.
- FIG. 1 illustrates the green and sintered densities of bioceramic samples prepared from powders incorporating various amounts of NaCl as the porogen.
- FIG. 2 illustrates the green and sintered densities of bioceramic samples prepared from powders incorporating various amounts of graphite (sieved 150 - 600mm) as the porogen.
- FIG. 3 is a scanning electron microscope (SEM) image of a fracture surface of a a sintered bioceramic sample prepared without any porogen showing no macro porosity (magnification 5Ox).
- FIG. 4 is a SEM image of a fracture surface of a sample prepared with 44% graphite as the porogen showing the macro porosity arising from the elimination of the porogen (magnification 5Ox).
- FIG. 5 is a SEM image of a fracture surface of a sintered bioceramic sample prepared without any porogen showing retained micro porosity (magnification 5000x).
- FIG. 6 is a SEM image of a fracture surface of sintered bioceramic sample prepared without any porogen and subsequently infused with polycaprolactone at a ratio of
- FIG 7 illustrates the effect of the initial graphite content on the subsequent mass of the biopolymer PCL that can be incorporated in the final composite product.
- FIG. 8 illustrates the composite density as a function of initial graphite content. The higher the concentration of the less dense PCL in the bioceramic composite, the lower the overall density of the final composite product.
- FIG. 9 illustrates the ultimate compressive strength (UCS) of the final composite product as a function of mineral content.
- the UCS increases with an increase in the mineral content.
- FIG. 10 illustrates the 4-point bending strength as a function of mineral content of the final composite product. The bending strength increases with an increase in the mineral content.
- FIG. 11 illustrates the compressive modulus of the final composite product as a function of mineral content.
- the compressive modulus increases with an increase in the mineral content. Note: This data was generated from an Instron compression test and inherently incorporates the flexure of the test apparatus. Data from ultrasonic Young's Modulus testing indicate compressive modulus of 3.5 to 25 GPa for similar samples.
- FIG. 12 illustrates the bending modulus of the final composite product as a function of mineral content.
- the bending modulus increases with an increase in the mineral content.
- This data was generated from an Instron four point bending test and inherently incorporates the flexure of the test apparatus. Data from ultrasonic Young's Modulus testing indicate bending modulus of 4 to 70 GPa for similar samples.
- FIG. 15 illustrates Reitfeld refinement estimates of the concentration of each calcium phosphate phase present in the bioceramic after sintering with graphite, NaCl or without a pore former.
- FIG. 16 is a picture showing exemplary devices that can be constructed using the calcium phosphate and biopolymer composite of the invention.
- a biopolymer or “at least one biopolymer” may include a plurality of biopolymers, including mixtures thereof.
- a pharmaceutical agent or “at least one pharmaceutical agent” may include a plurality of pharmaceutical agents, including mixtures thereof.
- a bioceramic precursor composition or “at least one bioceramic precursor composition” may include a plurality of calcium phosphate based bioceramic precursors, including mixtures thereof.
- the terms “comprising”, “having”, “including” are intended to be open-ended and mean that there may be additional elements other than the listed elements
- bioceramic and/or bioceramic composite described herein may be used in the treatment of a variety of orthopedic and dental disorders, including but not limited to, healing or repairing bone voids, fractures, breaks and any other defects, preventing the collapse of two adjacent vertebrae, spinal or cervical fusion, and combinations thereof.
- "comprising,” “including,” “containing,” “characterized by,” and grammatical equivalents thereof are inclusive or open-ended terms that do not exclude additional, unrecited elements or method steps, but will also be understood to include the more restrictive terms “consisting of and “consisting essentially of.”
- biopolymer means one or more polymers that are biocompatible.
- Example 1 Preparation and Testing of a Bioceramic, including a Bioceramic Composite
- a silicon-substituted mixed-phase calcium phosphate species is precipitated from a reaction mixture of calcium hydroxide and o-phosphoric acid and aged with a silicon source added to the precipitate (see U.S. Patent 6,323,146).
- the precipitate is dried, crushed and calcined at 900°C for 1 hour.
- the crystalline product is then combined with polyethylene glycol, polyvinyl alcohol and a pore forming species and wet milled into a fine powder.
- the powder is then transferred into a die and pressed uniaxially under 1 A ton per cm 2 load (or approximately 50MPa) into various sample shapes, which are then fired for an hour at 1200 0 C to sinter the samples and to remove the porogen.
- the sintered samples with inherent porosity are infiltrated with alternate biopolymers (e.g. polycaprolactone) to produce the bioceramic and biopolymer composite.
- Graphite and sodium chloride were examined to determine their suitability as pore forming species in preparing porous sintered calcium phosphate ceramics.
- the influence of NaCl and graphite on the green and sintered densities of the bioceramic component is shown in Figures 1, 2.
- the level of porosity was found to be highly controllable and related to the quantity, particle size and amount of the incorporated porogen.
- the samples prepared with sodium chloride exhibited a significantly greater increase in porosity with increases in porogen concentration.
- Sodium chloride reduces shrinkage; consequently, the void fraction is greater for similar porogen addition levels.
- PCL Polycaprolactone
- the addition of a pore forming agent to the bioceramic powder has an influence on the final concentration of calcium phosphate phases present.
- the addition of graphite stabilizes the ⁇ -TCP phase, whereas the addition of salt promotes the formation of HA
- the porogens evaluated were: graphite, carbon black, NaCl, MgCl 2 , wood pulp and PVA.
- any particulate that is of 10 - 500 ⁇ m, or 75-300um, in size can be used as the pore forming agent and incorporated effectively into the wet-milled bioceramic precursor powder, where optionally the pore forming agent may be effectively dissolved or burnt out during sintering.
- the process of the invention may be adopted to produce orthopedic and dental implants in a variety of shapes and sizes ( Figure 16). These bioceramic composite devices retain high mechanical performance yet also provide for a wide range of implant customization techniques during operative placement and fixation. Furthermore, the biopolymer phase provides for the release of stored pharmaceutical agents at the site of implantation.
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Abstract
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009801184692A CN102036694A (en) | 2008-05-30 | 2009-06-01 | Bioceramic and biopolymer composite |
EP09758717.4A EP2296719A4 (en) | 2008-05-30 | 2009-06-01 | Bioceramic and biopolymer composite |
CA2724907A CA2724907A1 (en) | 2008-05-30 | 2009-06-01 | Bioceramic and biopolymer composite |
AU2009255648A AU2009255648A1 (en) | 2008-05-30 | 2009-06-01 | Bioceramic and biopolymer composite |
US12/955,109 US8399009B2 (en) | 2008-05-30 | 2010-11-29 | Bioceramic and biopolymer composite |
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US12/955,109 Continuation US8399009B2 (en) | 2008-05-30 | 2010-11-29 | Bioceramic and biopolymer composite |
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US (1) | US8399009B2 (en) |
EP (1) | EP2296719A4 (en) |
CN (1) | CN102036694A (en) |
AU (1) | AU2009255648A1 (en) |
CA (1) | CA2724907A1 (en) |
WO (1) | WO2009148553A2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102641523A (en) * | 2012-03-07 | 2012-08-22 | 中南大学 | Porous hydroxyapatite biological ceramic and preparation method thereof |
ES2404733A1 (en) * | 2011-10-05 | 2013-05-28 | Universidad De Extremadura | Bioactive hybrid scaffolding, method of manufacture and use for bone fabric engineering. (Machine-translation by Google Translate, not legally binding) |
Families Citing this family (6)
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US20110045233A1 (en) * | 2009-08-20 | 2011-02-24 | Sandra Lee Gray | Dimensional control during firing to form aluminum titanate honeycomb structures |
US9066998B2 (en) | 2012-03-02 | 2015-06-30 | Bio2 Technologies, Inc. | Devices and method for tissue engineering |
US10022889B2 (en) * | 2013-03-14 | 2018-07-17 | Stratasys, Inc. | Ceramic support structure |
CN103691000B (en) * | 2013-12-12 | 2015-08-05 | 西南交通大学 | The preparation method of micro-, nano-calcium phosphate/catechol based polyalcohol bone repairing support |
CN107525916A (en) * | 2017-03-15 | 2017-12-29 | 北京大学口腔医学院 | Simulate the microporous barrier piece of people's dentine |
CN116617455A (en) * | 2023-05-29 | 2023-08-22 | 重庆生物智能制造研究院 | Preparation method of porous biological ceramic artificial bone scaffold with bioactivity |
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US4673355A (en) * | 1982-10-25 | 1987-06-16 | Farris Edward T | Solid calcium phosphate materials |
BR9610357B1 (en) * | 1995-09-01 | 2011-05-03 | bioactive artificial sintered composition, apparent ceramic microporous structure, implantable device, process for culturing functional bone cells and kit for monitoring and quantifying the activity of said cells | |
ES2256273T3 (en) * | 2000-08-04 | 2006-07-16 | Orthogem Limited | PORE SYNTHETIC OSEO GRAFT AND MANUFACTURING METHOD |
WO2003035576A1 (en) * | 2001-10-21 | 2003-05-01 | National Institute Of Advanced Industrial Science And Technology | Porous article of sintered calcium phosphate, process for producing the same and artificial bone and histomorphological scaffold using the same |
US6993406B1 (en) * | 2003-04-24 | 2006-01-31 | Sandia Corporation | Method for making a bio-compatible scaffold |
DE10328892A1 (en) * | 2003-06-26 | 2005-05-12 | Curasan Ag | Bone building agent and manufacturing process |
CN1240637C (en) * | 2003-08-12 | 2006-02-08 | 四川大学 | Porous calcium phosphate bioceramic material and preparing method thereof |
WO2007044229A2 (en) * | 2005-09-28 | 2007-04-19 | Calcitec, Inc. | Surface treatments for calcium phosphate-based implants |
WO2008025122A1 (en) * | 2006-08-30 | 2008-03-06 | The University Of British Columbia | Bioceramic composite coatings and process for making same |
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2009
- 2009-06-01 AU AU2009255648A patent/AU2009255648A1/en not_active Abandoned
- 2009-06-01 CN CN2009801184692A patent/CN102036694A/en active Pending
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- 2009-06-01 WO PCT/US2009/003307 patent/WO2009148553A2/en active Application Filing
- 2009-06-01 EP EP09758717.4A patent/EP2296719A4/en not_active Withdrawn
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2010
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2404733A1 (en) * | 2011-10-05 | 2013-05-28 | Universidad De Extremadura | Bioactive hybrid scaffolding, method of manufacture and use for bone fabric engineering. (Machine-translation by Google Translate, not legally binding) |
CN102641523A (en) * | 2012-03-07 | 2012-08-22 | 中南大学 | Porous hydroxyapatite biological ceramic and preparation method thereof |
Also Published As
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US20110104231A1 (en) | 2011-05-05 |
WO2009148553A3 (en) | 2010-03-11 |
EP2296719A4 (en) | 2013-05-01 |
AU2009255648A1 (en) | 2009-12-10 |
CA2724907A1 (en) | 2009-12-10 |
CN102036694A (en) | 2011-04-27 |
US8399009B2 (en) | 2013-03-19 |
EP2296719A2 (en) | 2011-03-23 |
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