WO2017068492A1 - Dispositif médical de réparation osseuse et procédé pour le fabriquer - Google Patents

Dispositif médical de réparation osseuse et procédé pour le fabriquer Download PDF

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Publication number
WO2017068492A1
WO2017068492A1 PCT/IB2016/056244 IB2016056244W WO2017068492A1 WO 2017068492 A1 WO2017068492 A1 WO 2017068492A1 IB 2016056244 W IB2016056244 W IB 2016056244W WO 2017068492 A1 WO2017068492 A1 WO 2017068492A1
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Prior art keywords
medical device
bioactive
composite particles
polymer
metal
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PCT/IB2016/056244
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English (en)
Inventor
Andrew Mcneill
Duncan SHARP
Lucie DE BEAUCHAMP
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Taragenyx Limited
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Publication of WO2017068492A1 publication Critical patent/WO2017068492A1/fr

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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
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • 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
    • 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
    • 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
    • A61L27/14—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention relates to a medical device and methods for producing the device.
  • a range of materials has been used for the construction of medical implants. These include titanium (Ti) and its alloys, cobalt and its alloys, chromium and its alloys and polyether ether ketone (PEEK). These materials have been chosen for their biocompatibility, mechanical properties and resistance to corrosion. However, clinical applications require a broader range of benefits than just these properties. Additional benefits may include enhanced osseointegrative properties and resistance to infection.
  • Ti titanium
  • PEEK polyether ether ketone
  • PEEK as a material can be constructed into medical implants and requires the addition of bioactive particles in order to address wider clinical properties such as osseoconduction and anti-microbial effects.
  • These particles can be introduced to the PEEK via processes such as compounding (EP2675838). Once these particles are introduced homogenously throughout the bulk plastic, machining of the plastic into an implant will expose some of these particles on the surface of the implant, thereby imparting bio-active properties to an otherwise bio-inert surface.
  • the amount and composition of the particles may compromise the mechanical properties of the final implant.
  • the proportion of particles in the final implant is limited.
  • ensuring the correct ratio of bioactive materials in the final implants manufactured from compounded materials is difficult if more than one bioactive material is included.
  • Ceramics such as calcium phosphates have previously been included in PEEK using compounding techniques (WO2012/1 10803). This has successfully increased the osteoconductive properties of the implants manufactured using these compounded materials. As discussed above, it is however difficult to conventionally introduce an additional bioactive material along with the ceramics.
  • the present inventors have developed a method for compounding composite bioactive particles with polymer binder materials such that additional properties may be imparted to the implant. These additional properties may include increased osseointegrative or antimicrobial properties.
  • the present invention provides a medical device (or a component of such a device) which comprises a polymer binder and bioactive composite particles therein.
  • the present invention provides a method for the manufacture of a medical device or a medical device component that comprises: A) coating bioactive particles with a bioactive material to form bioactive composite particles; B) mixing a polymer binder and the bioactive composite particles produced in step A) and melting the binder using a screw extruder; C) manufacturing a medical device or a medical device component from the mixture produced in step B) by moulding.
  • Figure 1 shows a microscope image (x750) of the bioactive composite particles within a polymer substrate according to the present invention (25 wt% particles : 75 wt% polymer);
  • Figure 2 shows an SEM micrograph (x 2.28K) of bioactive composite particles within a polymer substrate according to the present invention (15 wt% particles : 85 wt% polymer); and Figure 3 shows an SEM micrograph (x 4.46K) of a particle within the same sample as shown in Figure 2.
  • the present invention relates to the manufacture of medical devices and medical device components and to the device and components so formed.
  • the term “medical device” is defined as an instrument, apparatus, implant, or similar or related article that is used to prevent, treat disease or other conditions, and may achieve at least part of its purpose by the inclusion of a bioactive material.
  • the medical device may be any type of device that is suitable for implantation into the human or animal body, for example for the purposes of bone grafting (a surgical procedure that allows for the replacement of missing bone, for example due to complex fractures).
  • the medical device is typically an orthopaedic (including spinal and maxillofacial) or dental implant.
  • the medical device may be a spinal cage, hip or knee (femoral, tibial, patella component) replacement/implant, femoral stem, acetabular cup, intramedullary nail or an internal and/or external fixator that is used in surgery, for example trauma surgery.
  • medical device component is defined as a component from which a medical device may be manufactured directly, for example by melting and moulding.
  • the manufacture of medical device components is an intermediate step in the manufacture of complete medical devices.
  • bioactive material means a chemical, protein or cellular material which has an effect on cells, for example an antimicrobial (for example antibacterial, antifungal or antiviral), osteoinductive, osteoconductive, angiogenic, antithrombotic, analgesic, pro-proliferative, anti-inflammatory, anti- rejection, anti-carcinogenic effect.
  • bioactive particle means a particle that includes at least one bioactive material as defined herein.
  • the present invention provides a method for the manufacture of medical device or a medical device component that comprises: A) coating bioactive particles with a bioactive material to form bioactive composite particles; B) mixing a polymer binder, and the bioactive composite particles produced in step A), and melting the polymer binder using a screw extruder; C) manufacturing a medical device or a medical device component from the mixture produced in step B) by moulding.
  • the bioactive composite particles employed in the method of the invention comprise bioactive particles coated with a bioactive material which comprises a particle core and a coating on the core.
  • the bioactive particles can be completely covered in the bioactive coat material.
  • the coating can be continuous or discontinuous.
  • the coat material can be present in over only a portion of the particle core surface area, for example the coating is present in patches or only partly coats the particle core.
  • the bioactive composite particles typically have a core of at least one first material, including at least one bioactive material, and a coat of a second material.
  • the second material is different to the first material.
  • the second material can comprise a biological material.
  • the particle core is encapsulated in the coat, which comprises another bioactive material.
  • the bioactive material used to coat the bioactive particles is different from the bioactive material that is present in the bioactive particle core.
  • one or both the core bioactive particles and the bioactive material coat may independently comprise more than one material and there may be more than one coat of bioactive material applied to each bioactive particle core.
  • the coating may be a discontinuous (patchy) coating which is optionally present across the whole surface area of the particle core.
  • the particle coating is present over the whole particle and is a discontinuous coating, i.e. small areas of core are accessible through small holes or "holidays" within the coating.
  • the particle benefits from the presence of the coating, but access to the particle core, for example for bone ingrowth, is also possible.
  • a calcium phosphate particle core for example of hydroxyapatite
  • a metallic coating for example titanium or titanium alloy.
  • Methods of particle coating that can be used to provide the bioactive composite particles for the method include but are not limited to chemical or physical vapour deposition (PVD), electroplating, dip coating, sputtering or molecular beam epitaxy (MBE) although other coating processes are possible.
  • PVD chemical or physical vapour deposition
  • electroplating electroplating
  • dip coating dip coating
  • sputtering molecular beam epitaxy
  • Vapour deposition is particularly useful in many cases, for example in coating ceramic particles with a metal where the technique can provide metal coated or encapsulated particles with an even layer of the metal of a controlled thickness.
  • titanium coated hydroxyapatite bioactive composite particles can be made by vapour deposition of titanium on hydroxyapatite as described in the applicant's own earlier application published as WO2010/136777, which is incorporated herein by reference.
  • the coated particles had a core of low density hydroxyapatite, i.e. the hydroxyapatite had a density below 1 g/cm 3 .
  • the low density selected enabled the coated particles to form a coat on an article by spray coating.
  • hydroxyapatite particles can be individually coated with titanium or titanium alloy by using vapour deposition techniques that include means to prevent aggregation of the particles during processing. For example a vibrating table, rotating cup or tumble drier, each of which agitates the particles during the deposition process.
  • vapour deposition techniques that include means to prevent aggregation of the particles during processing.
  • a vibrating table, rotating cup or tumble drier each of which agitates the particles during the deposition process.
  • the same method could also be used for other metals, for example vanadium, aluminium, chromium, cobalt, steel, iron, gallium, lithium, strontium, magnesium, copper, zinc, silver and a salt, mineral, or alloy of any of these metals, typically zinc, copper, iron, silver, gold, strontium, or metallic alloys.
  • the particle core material may comprise, substantially comprise or consist of materials selected from the group consisting of ceramics, silicon-based compounds, polymers, metals, metal alloys and combinations thereof.
  • the particle core material may comprise, substantially comprise or consist of a material selected from the group consisting of ceramics and silicon-based compounds.
  • the particle coat material may comprise, substantially comprise or consist of materials selected from the group consisting of ceramics, silicon-based compounds, polymers, metals, metal alloys and combinations thereof.
  • the particle coat material may comprise, substantially comprise or consist of a material selected from the group consisting of metals and metal alloys.
  • the metal and metal alloys are titanium, vanadium, aluminium, chromium, cobalt, steel, iron, gallium, lithium, strontium, magnesium, copper, zinc, silver and a salt, mineral, or an alloy of any of these metals, for example are titanium, iron, copper, strontium, silver, gold, or combinations or alloys thereof.
  • particle cores or a particle coat may consist of a chosen inorganic salt, mineral, or organic compound.
  • a powdered ceramic or silicon-based compound is included in the bioactive composite particles produced in step A).
  • the powdered ceramic or silicon-based compound comprises a phosphate and/or sulphate.
  • the ceramic or silicon-based compound comprises at least one compound selected from the group consisting of calcium phosphate, calcium carbonate, calcium sulfate, substituted-calcium phosphate, silicon oxide, silicon dioxide, silicon phosphate, silicon carbonate and composites and crystalline forms thereof.
  • the ceramic compound comprises and apatite, for example hydroxyapatite (HA).
  • the ceramic compound comprises tricalcium phosphate.
  • the particle core comprises calcium phosphate (such as hydroxyapatite) which is a sintered hydroxyapatite.
  • the particle core can be coated with titanium or titanium alloy.
  • the particle core has a density of at least 2 g/cm 3 , for example from 2 to 3.2 g/cm 3 , for example 2.5 to 3.1 g/cm 3 , for example 2.5 to 3.0 g/cm 3 , for example 2.6 to 3.0 g/cm 3 (such as 2.7 g/cm 3 , 2.8 g/cm 3 , or 2.9 g/cm 3 ).
  • Sintered hydroxyapatite is suitable for such a particle core, for example sintered hydroxyapatite.
  • the particle core can be coated with titanium or titanium alloy.
  • the bioactive composite particles consist of a bioactive particle core and a coating of a bioactive material.
  • the core of the bioactive composite particles includes a bioactive material such as hydroxyapatite. Alternatively the core of the particles may include a non-bioactive material such as silica.
  • the particle core typically ranges in diameter from 1 pm to 500 pm, for example from 2 pm to 400 pm, from 3 pm to 300 pm, from 4 pm to 200 pm, from 5 pm to 100 pm or from 10 m to 50 pm.
  • the particle cores may have a diameter in the range of up to 200 pm, for example up to 150 pm.
  • the particle cores may have a diameter of from 10 to 200 pm, for example 10 to 150 pm, 10 to 100 pm, 10 to 80 pm, 20 to 100 pm, 20 to 80 pm, 20 to 60 pm, 20 to 50 pm.
  • a metal is included in the bioactive composite particles produced in step A).
  • the metal comprises at least one metal selected from the group consisting of titanium, vanadium, aluminium, chromium, cobalt, steel, iron, gallium, lithium, strontium, magnesium, copper, zinc, silver and a salt, mineral, or alloy of any of these metals.
  • the metal is silver.
  • the metal component of the bioactive composite particles forms the particle coating of the bioactive composite particles.
  • the metal coating on these bioactive composite particles may be of a thickness that ranges from 1 pm to 50 pm, for example 2 pm to 40 pm, from 3 pm to 30 pm, from 4 pm to 20 pm or from 5 pm to 10 pm.
  • the bioactive composite particles includes a bioactive agent.
  • the bioactive agent can be an antibiotic.
  • the antibiotic may, for example be an aminoglycoside, ⁇ -lactam, macrolide, cephalosporin, lincosamide, fluoroquinolone, glycopeptide antibiotic and/or a lipopeptide antibiotic. Suitable antibiotics include gentamycin, erythromycin, tobramycin, vancomycin and daptomycin.
  • one of the bioactive materials in the bioactive composite particles is a chelating agent, for example ethylenediaminetetraacetic acid (EDTA). Chelating agents are used, for example, to remove heavy metals from the body.
  • one of the bioactive materials in the bioactive composite particles is a growth factor, for example a bone morphogenetic protein.
  • the growth factor may be bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), a protein from the transforming growth factor beta (TGF- ⁇ ) superfamily or a combination of any thereof.
  • BMP-2 bone morphogenetic protein-2
  • BMP-7 bone morphogenetic protein-7
  • VEGF vascular endothelial growth factor
  • PDGF platelet-derived growth factor
  • TGF- ⁇ transforming growth factor beta
  • one of the bioactive materials in the bioactive composite particles is a bioactive metal, typically an antimicrobial metal, for example silver, strontium, magnesium, lithium, gallium, copper, iron or a salt or alloy of any of these materials.
  • Bioactive composite particles produced by the method of the invention typically comprise a ceramic or silicon-based core with a bioactive metal coating. This enables the two or more bioactive materials to be compounded with polymer binder materials without detrimental effects on the mechanical properties of the resulting medical devices manufactured from them. Further benefits include delivering the bioactive materials at clearly defined ratios and enabling synergistic co-localisation of different bioactive materials in the implant. This is difficult to achieve conventionally using two different powders with separate components. The co-localisation of materials with different mechanical properties may also improve cellular response to the resulting implant.
  • the bioactive composite particles comprise a metal core with a ceramic or silicon-based coating.
  • the bioactive composite particles comprise a ceramic or silicon-based core with a coating of an antibiotic.
  • hydroxyapatite particles can be coated with gentamicin before being compounded with poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL).
  • the bioactive metals are useful in a number of therapeutic applications and are more chemically robust than growth factors or antibiotics.
  • the ceramic or silicon- based compound promotes osteoconduction.
  • the medical device has mechanical properties complying with the standards set for orthopaedic implants. In some embodiments, this is achieved by the inclusion of a polymer binder in the medical device.
  • polymer binder is defined as the use of a polymer to bind the other components of the medical device together, and play a predominantly structural role in the implant.
  • the polymer binder includes phenyl moieties, ketone moieties and/or ether moieties.
  • the polymer binder may be at least one polymer selected from the group consisting of polyetheretherketone (PEEK), polyaryletherketone (PAEK), poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL).
  • PEEK polyetheretherketone
  • PAEK polyaryletherketone
  • PLGA poly(lactic-co-glycolic acid)
  • PCL polycaprolactone
  • the polymer binder comprises a biodegradable polymer derived from lactide (LA), glycolide (GA), caprolactone (CL) and/or poly(ethylene glycol) (PEG).
  • LA can be D-L-lactide (DLLA), L-lactide (LLA), D- lactide (DLA), meso-lactide (mLA) or a combination thereof.
  • the polymers binders described above act as a binder for the compounding process. Typically these binders form the majority of the resulting medical devices, for example at least 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% by weight of the implant.
  • the polymer binder and the bioactive composite particles are mixed together and the polymer binder melted using a screw extruder.
  • a twin screw extruder is used to mix the polymer binder with the bioactive composite particles, and to melt the polymer binder.
  • the output of the screw extruder may be used to form a medical device directly, or may produce medical device components, for example discrete units of the compounded material. These discrete units may be in the form of pellets, which are subsequently used to form medical devices by melting and moulding.
  • the medical device is formed by injection moulding following melting of the compounded material.
  • the term "compounded material" is defined as a material comprising both polymer binder and bioactive composite particles.
  • the medical device manufactured according to the present invention typically has a tensile strength and/or compressive strength of at least or greater than 15MPa, at least 20 MPa, at least 23 MPa, at least 25 MPa, at least 30 MPa, at least 35 MPa, at least 40 MPA, at least 45 MPa or at least 50 MPa.
  • HA-Ti particles were produced using hydroxyapatite particles having a size of 40 ⁇ 20 pm.
  • a titanium coating of 5 to 10 pm was applied over each particle using a physical vapour deposition method (PVD).
  • PVD physical vapour deposition method
  • the HA-Ti particles were produced as described in Example 1.
  • PEEK 380P sini-crystalline powder
  • the HA-Ti particles were added to the molten polymer binder so that the admixture contained 25% (by weight) of the HA-Ti particles and 75 % (by weight) of PEEK.
  • the admixture was blended and formed into a slab (approximately 5cm x 5cm) by compression moulding for further analysis.
  • Figure 1 shows a microscope image of sample of the slab at x750 magnification demonstrating that the particles are evenly dispersed throughout the PEEK polymer.
  • Example 2 was repeated, except that amount of HA-Ti particles was adjusted so that the molten admixture contained 15% (by weight) of HA-Ti particles and 85 % (by weight) of PEEK. Again the admixture was blended and formed into a slab (approximately 5cm x 5cm) by compression moulding for further analysis before examination by microscopic analysis of a cross-section.
  • Figure 2 shows a close-up detail from an SEM micrograph of particle embedded within the PEEK polymer (2.28K magnification) whilst Figure 3 is a further close up SEM micrograph (x 4.46K magnification) of a cross-section of a single particle from Figure 2 showing the interior of the hydroxyapatite core and the titanium coating visible around the particle edge.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Biomedical Technology (AREA)
  • Inorganic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)

Abstract

L'invention concerne un dispositif médical (ou un composant de celui-ci) approprié pour la réparation osseuse et un procédé pour fabriquer le dispositif. Le dispositif médical comprend des particules composites comprenant un noyau biologiquement actif et un revêtement biologiquement actif, les particules étant incorporées dans un liant polymère moulé pour obtenir la forme requise. Dans un mode de réalisation, le noyau des particules peut être un matériau d'ostéo-intégration, tel que le phosphate de calcium, et le revêtement biologique peut être un métal ou alliage métallique, tel que du titane ou un alliage de titane. Le liant polymère peut être du PEEK. Le procédé comprend les étapes consistant à : A) recouvrir des particules bioactives avec un matériau bioactif afin de former des particules composites bioactives ; B) mélanger un liant polymère et les particules composites bioactives produites à l'étape (A) et faire fondre le liant au moyen d'une extrudeuse à vis ; C) fabriquer, par moulage, un dispositif médical ou un composant de dispositif médical à partir du mélange produit à l'étape (B).
PCT/IB2016/056244 2015-10-19 2016-10-18 Dispositif médical de réparation osseuse et procédé pour le fabriquer WO2017068492A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1518465.8A GB2544261A (en) 2015-10-19 2015-10-19 Method
GB1518465.8 2015-10-19

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