WO2020161239A1 - Implant médical à base de phosphate de calcium-métal bioactif poreux - Google Patents

Implant médical à base de phosphate de calcium-métal bioactif poreux Download PDF

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Publication number
WO2020161239A1
WO2020161239A1 PCT/EP2020/052997 EP2020052997W WO2020161239A1 WO 2020161239 A1 WO2020161239 A1 WO 2020161239A1 EP 2020052997 W EP2020052997 W EP 2020052997W WO 2020161239 A1 WO2020161239 A1 WO 2020161239A1
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Prior art keywords
calcium phosphate
particles
slurry
medical implant
metal
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PCT/EP2020/052997
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English (en)
Inventor
Jiaping LI
Lorenzo Moroni
Pamela HABIBOVIC
Clemens Van Blitterswijk
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Universiteit Maastricht
Academisch Ziekenhuis Maastricht
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Publication of WO2020161239A1 publication Critical patent/WO2020161239A1/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
    • A61L27/50—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
    • 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
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • 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
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/427—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L27/422 or A61L27/425
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/08—Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
    • 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
    • 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
    • A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
    • 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
    • A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction

Definitions

  • the present invention relates to a medical implant comprising a porous composite wherein the porous composite contains metal particles and calcium phosphate particles.
  • the invention further relates to a method of making such a medical implant.
  • the invention also relates to a composition for making the medical implant.
  • Medical implants are often made of biocompatible metals. These metals such as titanium (Ti) and its alloys have good mechanical and chemical properties, like high fracture toughness and flexural strength and good corrosion resistance, making them widely used materials in e.g. orthopedic and craniomaxillofacial applications.
  • Ti titanium
  • its alloys have good mechanical and chemical properties, like high fracture toughness and flexural strength and good corrosion resistance, making them widely used materials in e.g. orthopedic and craniomaxillofacial applications.
  • mechanical mismatch and consequent stress shielding between bone and metal implant results in irritation, inflammation, and implant loosening or failure.
  • the bioinertness of metal implants results in weak bonding with host bone.
  • CaP calcium phosphate
  • metal based orthopedic implants are often coated with a layer of calcium phosphate.
  • the poor interfacial strength between the metallic substrate and the coating as well as fracture of coating may result in implant loosening with serious clinical consequences.
  • Creating customized implants with inorganic biomaterials is typically constrained to one material only with current additive manufacturing methods such as selective laser melting (SLM) or electron beam melting (EBM). Indeed, it is challenging to make metal-calcium phosphate composites using SLM or EBM since the ceramic powder absorbs energy and cools slowly, creating local hot spots, which may cause overheating of the metal resulting in liquidification. In turn, thermal stresses are introduced that cause cracking. Another challenge is the control over powder feed rate of the ceramic powder, having a frictional resistance that is different from that of the metal powder.
  • SLM selective laser melting
  • EBM electron beam melting
  • hydroxyapatite nanoparticles of 50-100 nm
  • titanium particles of 45 pm.
  • the weight ratio of titanium to HA is exemplified as 1 :5.
  • Compressive strength is reported at 240 MPa.
  • the present invention now provides a medical implant comprising a porous composite
  • porous composite contains metal particles and calcium phosphate particles
  • the metal particles have a particle size of 1 to 100 pm and the calcium phosphate particles have a particle size of 10 to 300 pm;
  • the composite contains 3 to 20 wt.% calcium phosphate particles based on the total weight of metal particles and calcium phosphate particles.
  • medical implant is meant a device or tissue placed inside or on the surface of a body, to replace a missing structure, support a damaged structure or enhance an existing structure.
  • the medical implant is a bone implant, more in particular an orthopedic or dental implant.
  • Orthopedic implants are implants that replace a missing joint or bone or support damaged bone.
  • medical implants of the invention are screws, nails, plates, joints and bones.
  • orthopedic implants are hip implants, including hip sockets, balls and stems, knee implants, spinal implants and craniomaxillofacial implants (skull and jaw).
  • the metal particles in the composite are preferably spherical particles.
  • spherical the normal definition is meant, e.g. round, globular or ball-shaped.
  • the aspect ratio (length/diameter, L/D) of the particles is approximately 1 , i.e. from 0.9 to 1.
  • the particle size of the metal particles and the calcium phosphate particles in the composite can for instance be determined by electron microscopy, in particular resulting in a number distribution of the particle size, or by sieving, in particular resulting in a mass distribution of the particle size.
  • the particle size of the metal particles is 1 to 100 pm. If the particle size is smallerthan 1 pm the metal particles are not stable. Preferably, the particle size is more than 10 pm, more preferably more than 20 pm, in particular more than 25 pm.
  • the particle size of the metal particles is larger than 100 pm, it becomes difficult to process the particles to obtain the composite.
  • the particle size of the metal particles is less than 80 pm, more preferably less than 60 pm.
  • the metal particles preferably have a particle size distribution with a D50 of 25-35 pm and a D90 of 50-60 pm.
  • any biocompatible metal can be used.
  • the metal is selected from the group consisting of titanium, cobalt, chromium, aluminum, molybdenum, tantalum, magnesium, stainless steel, nickel, tungsten and alloys thereof.
  • alloys are Ti6AI4V, an alloy of titanium, aluminum and vanadium, or cobalt-chromium alloys.
  • the metal is selected from the group consisting of titanium, molybdenum, chromium, tantalum, magnesium, cobalt and alloys thereof.
  • titanium or a titanium alloy is used.
  • the preferred titanium alloy is
  • alloy is meant a substance made by melting two or more elements together, at least one of them metal.
  • An alloy crystallizes upon cooling into a solid solution, mixture, or intermetallic compound. The components of alloys cannot be separated using a physical means.
  • An alloy is homogeneous and retains the properties of a metal.
  • the particle size of the calcium phosphate particles is 10 to 300 pm.
  • the particle size of the calcium phosphate particles is at least 50 pm, more preferably at least 60 pm.
  • the particles size is at most 300 pm, preferably at most 250 pm, most preferably at most 125 pm.
  • the particle size of the calcium phosphate particles is important to ensure the right distribution of metal and calcium phosphate particles which results in the desired mechanical properties of the composite. It is also important for inducing bone growth (osteoinduction).
  • the calcium phosphate particles preferably have a particle size distribution with a D50 of 65-75 pm and a D90 of 120-140 pm.
  • osteoinduction is meant that primitive, undifferentiated and pluripotent cells are stimulated to develop into the bone-forming cell lineage, thus stimulating bone growth.
  • osteoinduction see Eur.Spine J (2001) 10: S96-S101.
  • the calcium phosphate particles may comprise any biocompatible calcium phosphate such as tricalcium phosphate, hydroxyapatite, biphasic calcium phosphate and bioglass and mixtures thereof.
  • Biphasic calcium phosphate is a mixture of hydroxyapatite and tricalcium phosphate.
  • tricalcium phosphate is that it is less likely to cause formation of CaTi0 3 at the interface of the calcium phosphate and titanium particles when the composite is sintered at high temperatures, e.g. above 800 °C.
  • the composite obtained with tricalcium phosphate is less brittle than that obtained with hydroxyapatite only. More preferably, b-tricalcium phosphate is used.
  • the aspect ratio (L/D) of the calcium phosphate particles is preferably from 0.4 to 1.
  • the calcium phosphate particles are the same size as the metal particles or larger, i.e. the ratio of particle size calcium phosphate to particles size metal is from 1 : 1 to 15: 1.
  • micropores can be found from sintering of the metal particles.
  • the calcium phosphate particles create a nanoporous structure.
  • the composite is porous, i.e. the material has holes or voids.
  • Porosity is a common measure to determine the extent to which a material is porous.
  • the present composite has a porosity of from 35% to 90%, preferably from 50% to 85%. Total porosity can be measured by determining the weight to volume ratio. Also mercury porosimetry can be used.
  • the composite further has good mechanical properties as expressed by the Young’s modulus and compressive strength. These properties will depend on the porosity of the composite.
  • the Young’s modulus is from 0.1 to 10 GPa.
  • the compressive strength is about 100 MPa with a porosity of around 65 %, If porosity is higher, Young’s modulus and compressive strength will generally be lower.
  • the metal provides the structural strength of the implant, whereas the calcium phosphate ensures compatibility with the bone tissue. It is therefore important to have the right ratio of metal to calcium phosphate.
  • the composite contains 3 to 20 wt.% calcium phosphate particles based on the total weight of metal particles and calcium phosphate particles. Preferably, the composite contains 5 to 15 wt.% calcium phosphate particles.
  • the composite can further contain minor amounts of other components, e.g. bioglass.
  • Bioglass can improve the sintering ability of the composite and also the biological properties due to the presence of other minerals such as Si0 2 , CaO and Na 2 0.
  • the medical implant of the invention comprises at least 95 wt.% of the composite, based on the total weight of the composite.
  • the medical implant comprises a metal base, coated with the composite.
  • the metal base is made of a biocompatible metal, preferably the same metal as in the composite.
  • the metal particles in the composite are titanium particles
  • the metal base is preferably titanium.
  • an intermediate coating layer of metal particles is present between the metal base and the composite coating. The metal particles in the intermediate coating layer have preferably the same properties as the metal particles in the composite coating.
  • the present invention relates to a method of making the medical implant.
  • the method comprises the steps of: • providing a slurry of metal particles and calcium phosphate particles in a medium;
  • the metal particles are spherical and have a particle size of 1 to 100 pm; wherein the calcium phosphate particles have a particle size of 10 to 300 pm; wherein the composite contains 3 to 20 wt.% calcium phosphate particles based on the total weight of metal particles and calcium phosphate particles.
  • metal particles and calcium phosphate particles are as described above for the composite.
  • the medium for the slurry is not critical and any type of medium known in the art for providing a ceramic slurry can be used.
  • the medium is for instance a suspension or solution of a binder in an aqueous or organic solvent.
  • the binder will generally be removable by heating.
  • the main requirement for the binder is that it bonds the metal particles and calcium phosphate particles prior to sintering. Since the binder is volatilized and thus removed during sintering, there is no requirement that the binder is biocompatible.
  • Suitable binders are: methylcellulose, hydroxypropyl methylcellulose, polyvinylalcohol (PVA), polyethylene glycol, polyvinylpyrrolidone (PVP). These binders can be dissolved in water.
  • the concentration of the metal and calcium phosphate particles in the medium is not critical as long as the concentration is such that the slurry has suitable rheological properties such as viscosity to use it in the method of the invention. The higher this concentration, the higher the viscosity.
  • the weight ratio medium : (metal and calcium phosphate particles) is from 10: 1 to 1 : 10 w/w. For example a weight ratio of around 1 :6 can be used.
  • the use of a slurry system according to the invention has the advantage that the calcium phosphate powder is evenly distributed among the metal particles.
  • the method of making the medical implant may further comprise a step of drying the shape before sintering.
  • the drying step can take place under reduced pressure or in an atmosphere of inert gas.
  • the drying step is generally carried out at a temperature of from 15 to 60 °C for a period of 1 hour to 24 hours.
  • the goal of the drying step is to gradually remove the solvent (water) contained in the binder while maintaining the structural integrity of the shape.
  • the temperature for sintering the shape in the method above is at least 1000 °C, preferably at least 1 100 °C. Sintering can be carried out by placing the shape in a conventional oven. During this step also the binder is removed by decomposition at the elevated temperature.
  • the heating to at least 1000 °C can be gradual or step wise by increasing the temperature of the oven or placing the shape in ovens of different temperatures.
  • the method of the invention further has the advantage that no post-treatment after sintering is needed, e.g. it is not needed to remove any loose powder.
  • the invention provides two methods of making a medical implant.
  • a shape is created mostly consisting (e.g. more than 95%) of the composite of the invention.
  • This shape can be created by molding or by means of an additive manufacturing method such as a three dimensional (3D) printing method.
  • the composite of the invention is used to form a coating on a metal base.
  • the method of making the medical implant comprises the steps of:
  • a porogen such as urea is added to the slurry.
  • an additional step can be carried out, for instance by heating at a temperature of between 400 and 700 °C, but below the sintering temperature, to remove porogen and optionally a binder contained in the medium.
  • the method of making the medical implant comprises the steps of:
  • metal particles and calcium phosphate particles are as described above for the composite.
  • an additive manufacturing device such as a 3D printing device can be used.
  • the slurry is loaded in a syringe and forced through the syringe nozzle to create a fiber.
  • the step of depositing the slurry layer by layer comprises continuously deposing the fibers and layering the fibers down in alternating angles for each layer.
  • the fibers are laid down in a 90 degree angle compared to the previous layer.
  • metal particles and calcium phosphate particles of the invention ensures that the slurry can be readily deposited in a known additive manufacturing device with the right resolution and without clogging of the nozzle of the additive manufacturing device.
  • the slurry needs to have the appropriate viscosity.
  • the behavior of the slurry is non-Newtonian. A lower viscosity will result in deformation of the deposited fiber and gravity-induced flow subsequent to depositing, and a higher viscosity of slurry will cause a greater resistance against flowing and affect the quality of scaffold.
  • the optimal viscosity can be readily determined by a person skilled in the art based on these constraints.
  • the fiber rapidly solidifies when deposited in a layer, allowing to immediately build the next layer.
  • the dimensions of the fibers determine the porous structure of the composite.
  • the fibers will have a diameter of from 100 to 1000 pm, preferably around 500 pm.
  • the additive manufacturing method further not only mimics the shape and size of a defect area but also provides the mechanical and chemical properties to be functional for end use.
  • the layer-by-layer processing allows tight control over compositional gradients as well as physical features.
  • the implants made by the additive manufacturing process of the invention have the advantage that they possess an interconnected porous structure with macropores from 3D design, micropores from sintering of the metal particles and a nanoporous structure from the calcium phosphate particles.
  • additive manufacturing devices for the additive manufacturing method known additive manufacturing devices or 3D printers can be used.
  • the method of making the medical implant comprises the steps of:
  • metal particles have a particle size of 1 to 100 pm;
  • the calcium phosphate particles have a particle size of 10 to 300 pm; and wherein the slurry contains 3 to 20 wt.% calcium phosphate particles based on the total weight of metal particles and calcium phosphate particles.
  • the metal base is preferably made of the same metal as the metal particles.
  • metal particles and calcium phosphate particles are as described above for the composite.
  • the coating of the metal base with the slurry can be done by a method known in the art, for instance by dipping the metal base in the slurry, by spraying the slurry on the metal base or by pouring the slurry on the metal base. It is also possible to use additive manufacturing, or 3D printing, to deposit the coating.
  • the coating can have any suitable thickness but will generally be from 0.1 to 5 m , preferably 0.5 to 2 mm.
  • the method for coating a metal base can further comprise an additional step wherein before coating the metal base with the slurry of metal particles and calcium phosphate particles, an intermediate coating layer is applied of a slurry of metal particles.
  • the metal particles in the intermediate coating layer preferably have the same properties as the metal particles in the composite slurry, i.e. spherical particles with a particle size of 1 to 100 pm.
  • the metal in metal base, the composite coating and the intermediate coating layer is the same.
  • an implant is obtained having a titanium base, a titanium intermediate coating layer of titanium particles and a top coating of titanium particles and calcium phosphate particles.
  • the medium for the slurry is the same as mentioned above.
  • the binder ensures also that the coated construct (green body) can be physically handled prior to sintering without damaging the coating.
  • the invention thus also relates to a green body comprising a metal base, an intermediate coating of spherical metal particles having a particle size of 1 to 100 pm and a coating layer on the intermediate coating of metal particles and calcium phosphate particles according to the invention.
  • the invention also relates to a medical implant obtained by sintering the green body.
  • the coated implant obtained by the coating method has a shear strength of at least 27 MPa.
  • This shear strength represents the bond strength between the porous composite and the metal base.
  • the shear strength should be at least the overall shear strength of the metal base.
  • the present invention relates to a composition for making a medical implant, wherein the composition comprises a slurry of metal particles and calcium phosphate particles in a medium,
  • the metal particles are spherical and have a particle size of 1 to 100 pm; wherein the calcium phosphate particles have a particle size of 10 to 300 pm; wherein the composition contains 3 to 20 wt.% calcium phosphate particles based on the total weight of metal particles and calcium phosphate particles.
  • the preferred embodiments for the metal particles and calcium phosphate particles are as described above for the composite.
  • Such a composition can be a paste that can for instance directly be used in an additive manufacturing device.
  • the composition can be stored in a reservoir.
  • the invention thus also relates to a reservoir containing the composition described above, where the reservoir has a removable lid, ensuring absence of contact of the paste with the environment until use.
  • Examples of medical implants that can be made with the second method are the ball and socket of joints, preferably hip joints; the stem of a hip joint and dental implants.
  • Figure 1 shows 3D fiber deposition of a porous Ti-TCP scaffold
  • Figure 2 shows an Environmental Scanning Electron Microscopy (ESEM) photograph of a Ti-TCP composite with 5% TCP.
  • ESEM Environmental Scanning Electron Microscopy
  • Figure 3 shows an ESEM photograph of a Ti-TCP composite with 10% TCP.
  • Figure 4 shows an energy-dispersive X-ray (EDX) analysis of a Ti-TCP composite.
  • Figure 5 shows ESEM photographs of different Ti-TCP composites.
  • Figure 6 shows an ESEM photograph of a 3D Ti6AI14V-TCP coating on a Ti6AI14V plate.
  • Figure 7 shows an ESEM photograph of a 2D Ti6AI14V-TCP coating on a Ti6AI14V plate.
  • Figure 8 shows an ESEM photograph of a 3D Ti-TCP composite obtained using a porogen.
  • Figures 9A and 9B show ESEM photographs of starting material titanium particles (Fig. 9A) and starting material TCP particles (Fig. 9B).
  • Titanium (Ti) or Titanium alloy (Ti6AI4V) powder was obtained from AP&C advanced powder&coating, Canada, having a particle size of 45 pm.
  • Tricalcium phosphate was obtained from Xpand biotech, BV, Bilthoven, NL, particle size of below 500pm Methylcellulose was obtained from SigmaN LOT: 129H0078.
  • the TCP was pretreated by ball mill for one day, sieved with a mesh of 63 pm and 125 pm to obtain a TCP particle size of 63 pm to 125 pm. Titanium and TCP were mixed with an aqueous solution of methylcellulose at room temperature to obtain a homogenous slurry.
  • Particle size distribution obtained was as follows (see also Figure 9A and 9B):
  • Example 1 and Example 2 were used in a 3D fiber deposition process as follows.
  • a Bioplotter was used, consisting of a slurry dispensing unit having a syringe and nozzle; an air pressure plunger to regulate flow of slurry and a positional control unit linked to a personal computer containing software
  • the slurry was placed in a plastic syringe, through a fixation unit mounted on the “Y”-axis of the apparatus and kept at RT.
  • Air pressure (P) was applied to the syringe through a pressurized cap.
  • Rectangular block models were loaded on the Bioplotter CAM software.
  • the process involved depositing continuous fibers of material to produce two-dimensional (2D) layers with alternating 0/90 lay-down patterns of finite thickness and then building the 3D scaffold up layer-by-layer.
  • Figure 1 shows the processing of 3D fiber depositing porous Ti+TCP scaffold.
  • the nozzle used to extrude the slurry fibers is a stainless steel hypodermic needle.
  • the nozzle size is expressed as inner diameter of the nozzle, and a length of 16.1 mm.
  • a nozzle diameter of 500 pm was used.
  • fiber spacing was set to 0.5mm to create a pore size of around 450 pm since pore size around this range assures a rich blood supply, nutrient and waste exchange and promotes in growth of bone.
  • the thickness between fiber layers was kept at 400pm.
  • the samples were first dried for 24 hours at RT, then dried for 24 h at 50 °C, and finally sintered in flowing argon tube furnace or a high vacuum furnace applying a heating profile as follows: Gradual increase in temperature from room temperature to 500 °C, leave at 500 °C for 200 minutes, gradual increase to 1 150 °C, leave for 120 minutes, gradual cooling to room temperature.
  • Figure 2 shows an ESEM photograph of the construct obtained with the slurry of example 2 (5% TCP).
  • Figure 2A shows 70x magnification
  • Figure 2B shows 200x magnification.
  • Figure 3 shows an ESEM photograph of the construct obtained with the slurry of example 1 (10% TCP).
  • Figure 3A shows 60 x
  • Figure 3B shows 10Ox
  • Figure 3C shows 200x
  • Figure 4 shows EDX which shows no contamination during sintering and elemental analysis.
  • Example 1 and Example 2 Two comparative examples were carried out using the same compositions as in Example 1 and Example 2, but where TCP had a particle size of 125-250 pm (Comparative Example 1 and 2, respectively). The results are shown in Figure 5. Here it can be seen that with the larger TCP particles there are very few particles on the surface of the composite. Thus, the TCP is not so well distributed as in the Examples of the invention.
  • Slurry A and slurry B were prepared by mixing the components listed below at room temperature.
  • 1-octanol was obtained from Acros Organics, Pittsburgh, PA
  • Titanium alloy (Ti6AI14V) plates of 10x10x1 mm were used. The plates were first carefully cleaned in acetone for 15 minutes, then in 70% ethanol for 15 minutes and then in demineralized water for 15 minutes.
  • the plates were painted with slurry A to create a coating of titanium particles.
  • the painting was repeated 3 times to obtain a uniform thin layer of titanium particles on the plates.
  • 3D Ti-TCP made using the same 3D printing method as Example 1 and 2, with design pore size and structure was put on the Ti coated plate. Finally the obtained shape with the layer of Ti and layer of Ti-TCP is dried at 50 °C overnight. After drying, the samples are placed in a tube furnace with flowing argon for sintering. The furnace was set to the following temperature program: 500 °C for 180 minutes with flowing argon to remove binder, raising the temperature to 1 150 °C and sintering the product at this temperature for 150 minutes.
  • Figure 6 shows the resulting product.
  • Titanium alloy (Ti6AI14V) plates of 10x10x1 mm were used. The plates were first carefully cleaned in acetone for 15 minutes, then in 70% ethanol for 15 minutes and then in demineralized water for 15 minutes. Slurry B was painted onto the plates. The painting was repeated 3 times. The coated plates were dried and sintered as described in Example 3.
  • Figure 7 shows the resulting product.
  • Slurry C was prepared by mixing the materials described below:
  • Figure 8 shows the resulting product.
  • Example 1 The constructs obtained with the slurries of Example 1 and 2 were tested as an intramuscular implant in dogs.12 weeks after implantation, the construct with 10% TCP (example 1) showed the start of bone formation.

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Abstract

La présente invention concerne un implant médical qui comprend un composite poreux, le composite poreux contenant des particules métalliques, en particulier des particules sphériques de titane et des particules de phosphate de calcium. L'invention concerne en outre un procédé de fabrication d'un tel implant médical, par exemple par fabrication additive. L'invention concerne également une composition de fabrication de l'implant médical.
PCT/EP2020/052997 2019-02-07 2020-02-06 Implant médical à base de phosphate de calcium-métal bioactif poreux WO2020161239A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
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CN113332490A (zh) * 2021-06-08 2021-09-03 闽江学院 一种骨修复支架及其制备方法
CN114470317A (zh) * 2022-01-21 2022-05-13 江苏科技大学 一种颅骨修补用钛合金材料及其制备方法

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Publication number Priority date Publication date Assignee Title
KR20090116202A (ko) 2008-05-06 2009-11-11 한국기계연구원 다공성 티타늄-수산화인회석 복합지지체 및 이의 제조방법
WO2015009154A1 (fr) 2013-07-18 2015-01-22 Xpand Biotechnology B.V. Procédé permettant de produire un phosphate de calcium ostéo-inductif et produits ainsi obtenus
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WO2015009154A1 (fr) 2013-07-18 2015-01-22 Xpand Biotechnology B.V. Procédé permettant de produire un phosphate de calcium ostéo-inductif et produits ainsi obtenus
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MATERIALS TODAY, vol. 19, no. 2, March 2016 (2016-03-01)
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113332490A (zh) * 2021-06-08 2021-09-03 闽江学院 一种骨修复支架及其制备方法
CN114470317A (zh) * 2022-01-21 2022-05-13 江苏科技大学 一种颅骨修补用钛合金材料及其制备方法

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