EP2491167B1 - Procédés de dépôt de régions individuelles d'hydroxyapatite sur des implants médicaux - Google Patents

Procédés de dépôt de régions individuelles d'hydroxyapatite sur des implants médicaux Download PDF

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Publication number
EP2491167B1
EP2491167B1 EP10773461.8A EP10773461A EP2491167B1 EP 2491167 B1 EP2491167 B1 EP 2491167B1 EP 10773461 A EP10773461 A EP 10773461A EP 2491167 B1 EP2491167 B1 EP 2491167B1
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Prior art keywords
implant
calcium phosphate
ions
electrolyte solution
hydroxyapatite
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German (de)
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EP2491167A2 (fr
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Gautam Gupta
Andreas Sewing
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Biomet Manufacturing LLC
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Biomet Manufacturing LLC
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D9/00—Electrolytic coating other than with metals
    • C25D9/04—Electrolytic coating other than with metals with inorganic materials
    • C25D9/08—Electrolytic coating other than with metals with inorganic materials by cathodic processes
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D5/00—Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/18—Electroplating using modulated, pulsed or reversing current
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D5/00—Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/48—After-treatment of electroplated surfaces
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D5/00—Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/60—Electroplating characterised by the structure or texture of the layers
    • C25D5/615—Microstructure of the layers, e.g. mixed structure
    • C25D5/617—Crystalline layers

Definitions

  • the present technology relates to medical implants having discrete regions of a calcium phosphate (e.g., hydroxyapatite), and methods of their manufacture.
  • a calcium phosphate e.g., hydroxyapatite
  • CPP calcium phosphate phase
  • Hydroxyapatite is a biocompatible material similar in composition to the mineral content of natural bone.
  • hydroxyapatite coatings on medical orthopedic implants can enhance the implant's osteoconductive potential, among other things.
  • CPP coatings can be deposited onto electroconductive, or metal substrates using solution-based techniques, such as electrochemical deposition or sol-gel deposition.
  • One advantage of using such deposition processes is that they are not "line of sight" processes and thus can provide a complete coating coverage of complex shaped substrates. With the use of implants having nano-scale texturing, however, such deposition processes can be disadvantageous in that the coating may be applied over the nano-scale texturing, thereby negating its affect. Accordingly, there remains a need to provide methods for using electrochemical deposition techniques to provide discrete regions of CPP, including hydroxyapatite.
  • US 6,764,769 B2 discloses an apatite-coated metallic material, the coating of which consists of a covering of hydroxyapatite crystals and/or amorphous calcium phosphate spheres.
  • WO 98/13539 A1 discloses a method for coating a calcium phosphate compound onto a metallic material, the method comprising electrodepositing the calcium phosphate compound from an aqueous solution containing calcium ions, phosphate ions and a complex forming agent onto an electrode comprising the metallic material.
  • WO 2008/146113 A2 discloses a process for coating a surface of a metal element, the process comprising immersing into an electrolytic bath comprising collagen, calcium ions and phosphate ions a cathode and an anode, said cathode comprising the metal element to be coated.
  • US 5,310,464 discloses an electrolytic method for providing bone-emulating, phosphate coatings on prosthetic appliances.
  • the appliance is thereby immersed in a phosphate-containing electrolyte to serve as the cathode of the electrolysis process.
  • WO 98/09006 A1 discloses a method for electrochemical phosphating of metal surfaces by means of a cathodic process applying an aqueous phosphating solution.
  • US 2002/0084194 A1 discloses an article coated with an electrolytically deposited biocompatible composite layer useful as an internal prosthetic device.
  • the coating comprises hydroxyapatite and chitosan.
  • the present technology provides methods for electrochemically depositing one or more discrete, discontinuous regions of a calcium phosphate onto a medical implant.
  • the implant has at least one area having an electroconductive surface. At least a portion of the electroconductive surface is contacted with an electrolyte solution comprising calcium ions and phosphate ions. An electrical potential is applied between the electroconductive surface and the electrolyte solution. A plurality of discrete regions of a calcium phosphate phase is formed onto the electroconductive surface, wherein the calcium phosphate phase comprises a needle-shaped morphology.
  • the present invention provides a method for electrochemically depositing discrete discontinuous regions of a calcium phosphate comprising hydroxyapatite onto a metallic surface of a medical implant comprising at least one area having an electroconductive surface, the electroconductive surface having at least one nano-scale textured region, and wherein the electrochemical deposition is carried out in an electrolysis cell, or bath, in which at least the metallic surface of the implant is cathodically polarized, the method comprising:
  • the present invention provides a method for electrochemically depositing discrete discontinuous regions of a calcium phosphate comprising hydroxyapatite onto a metallic surface of a medical implant comprising at least one area having an electroconductive surface, the electroconductive surface having at least one nano-scale textured region, and wherein the electrochemical deposition is carried out in an electrolysis cell, or bath, in which at least the metallic surface of the implant is cathodically polarized, the method comprising:
  • the words “desirable”, “preferred” and “preferably” refer to embodiments of the technology that afford certain benefits, under certain circumstances. Furthermore, the recitation of one or more preferred or desired embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the technology.
  • the word "include,” and its variants, is intended to be non-limiting, such that recitation of items in a list is not to the exclusion of other like items that may also be useful in the materials, compositions, devices, and methods of this technology.
  • the terms “can” and “may” and their variants are intended to be non-limiting, such that recitation that an embodiment can or may comprise certain elements or features does not exclude other embodiments of the present technology that do not contain those elements or features.
  • compositions or processes specifically envisions embodiments consisting of, and consisting essentially of, A, B and C, excluding an element D that may be recited in the art, even though element D is not explicitly described as being excluded herein.
  • compositional percentages are by weight of the total composition, unless otherwise specified. Disclosures of ranges are, unless specified otherwise, inclusive of endpoints. Thus, for example, a range of "from A to B" or “from about A to about B” is inclusive of A and of B. Disclosure of values and ranges of values for specific parameters (such as temperatures, molecular weights, weight percentages, etc.) are not exclusive of other values and ranges of values useful herein.
  • the present technology provides methods for electrochemically depositing discrete, discontinuous regions of a calcium phosphate phase onto a medical implant.
  • Titanium and its alloys, in addition to other metal substrates, are becoming increasingly popular as implant materials due to their favorable biocompatibility and favorable mechanical and chemical properties.
  • Calcium phosphate phases (CPP) have a lot of bioactive potential, thus enabling chemical bonding to natural bone.
  • the main inorganic constituent CPP may contain amorphous calcium phosphate (Ca 9 (PO 4 ) 6 • nH 2 O), hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), octacalcium phosphate (Ca 8 H 2 (PO) 6 H 2 O), or brushite (CaHPO 4 • 2H 2 O), or mixtures thereof.
  • the CPP can additionally be doped with ions such as fluoride, silver, magnesium, carbonate, strontium, or sodium.
  • hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) is a CPP biocompatible material that is similar in composition to the major inorganic mineral content of natural bone.
  • hydroxyapatite coatings provided on metallic or otherwise electroconductive medical implants can enhance an implant's osteoconductivity potential.
  • Common deposition techniques for coating hydroxyapatite onto implants can include plasma spray coating, electrochemical deposition, and sol-gel deposition. While plasma spray coating is a widely used method, its high process conditions (high temperature) can result in coating properties that deviate from the mineral phase of bone, especially with respect to crystal structure and solubility.
  • the high process temperatures may cause partial decomposition of hydroxyapatite, resulting in the formation of other CPP, including amorphous calcium phosphate (ACP), ⁇ -tricalcium phosphate (TCP), ⁇ -TCP, tetracalcium phosphate, and calcium oxide.
  • ACP amorphous calcium phosphate
  • TCP ⁇ -tricalcium phosphate
  • ⁇ -TCP ⁇ -TCP
  • tetracalcium phosphate calcium oxide
  • ACP phase energetically favored places
  • Both the pre-layer and the spheres comprise clusters of Ca 3 (PO 4 ) 2 from which preferential crystalline hydroxyapatite needles grow: Ca 3 (PO 4 ) 2 + Ca 2+ + 2 OH - ⁇ Ca 10 (PO 4 ) 6 (OH) 2
  • a more efficient means of hydroxyapatite deposition may include the direct deposition of hydroxyapatite crystalline onto a metal substrate, or a more timely transformation to the crystalline phase.
  • Such a direct application can be beneficial where surfaces of the implant include nano-scale texturing or etching.
  • the present technology provides an electrochemical deposition process to facilitate an early transition from ACP to discrete deposition regions of hydroxyapatite crystalline, without the formation of a continuous layer of ACP as one would expect with such a deposition process. Unless one painstakingly masks various areas of the implant prior to the treatment, the typical electrochemical deposition process will first provide a continuous coating layer over the entire implant that is subsequently transformed into hydroxyapatite. Such a continuous coating would likely negate the various benefits obtained from any nano-scale etching or texturing.
  • the present technology surprisingly provides the electrochemical deposition of discrete regions of CPP, and hydroxyapatite in particular, onto the surface of a medical implant.
  • the present technology affects the kinetics of reaction, which can be controlled with the appropriate electrochemical parameters, as discussed below.
  • it provides a CPP deposition that is predominantly needle-shaped hydroxyapatite after only a short duration of time.
  • from about 70 to about 90 percent, or from about 85 to about 90 percent of the discrete CPP regions may have a crystalline structure, while only from about 10 to about 30 percent of the CPP may be an amorphous phase.
  • This can provide for calcium phosphate regions of variable solubility.
  • it may be preferred that the hydroxyapatite has a random orientation.
  • a medical implant including at least one area having an electroconductive surface.
  • the electroconductive surface can be a discrete area or it can be a continuous area covering the surface of the entire implant.
  • the surface is provided with nano-scale texturing.
  • Such an electroconductive surface can comprise a material selected from the group consisting of titanium, a titanium alloy, titanium nitrate, a CoCrMo alloy, stainless steel, an electroconductive polymer, and mixtures thereof.
  • the electrochemical deposition can be carried out in an electrolysis cell, or bath, in which at least the metallic surface of the implant is cathodically polarized.
  • a three-electrode arrangement can be made including a calomel electrode used as a reference electrode, a platinum sheet or gauze used as the counter electrode, and the metallic implant provided as the cathode.
  • the deposition process can take place biomimetically, near physiological pH and temperature conditions.
  • the electroconductive surface is placed in contact with an electrolyte solution comprising calcium ions and phosphate ions.
  • the electrolyte can comprise a Ca 2+ /H x PO 4 (3-x)- containing solution.
  • the ratio of the concentration of the calcium ions and the phosphate ions is chosen such that it is equal or at least equivalent to their concentrations in hydroxyapatite.
  • the electrolyte solution may include calcium chloride, calcium chloride dihydrate, or calcium acetate as the source of calcium ions, and ammonium dihydrogen phosphate as the source of phosphate ions.
  • the choice of the particular salts used may be based on availability.
  • the electrolyte solution is prepared using solutions that correspond to a final concentration of calcium:phosphate of about 1.7:1 (e.g., 1.67:1).
  • a final concentration of calcium:phosphate of about 1.7:1 e.g., 1.67:1.
  • one embodiment currently provides for a standard-like concentration of calcium ions of about 1.7 mM (e.g., 1.7 mM) and a concentration of phosphate ions of about 1.0 mM.
  • concentration calls for the electrical potential to be applied for 2 to 5 minutes, preferably about 2.5 minutes, in order to obtain desired deposition.
  • the concentration of calcium ions may be provided at about 0.2 mM (e.g., 0.167 mM) while the phosphate ions are provided at about 0.1 mM.
  • an addition modification includes applying the electrical potential having a similar current density for a slightly longer period of time. With such a lower concentration of ions, the electrical potential isapplied for about 10 minutes, in order to obtain desired deposition. Even with the variance in the concentration levels, it is envisioned that the current density will still be applied at about the same level, or slightly lower, as will be discussed. It should be understood that the actual current density required may vary for each different type of component processed, and may depend upon the total surface area and surface finish, as well as the power sources available.
  • an electrical potential is applied between the electroconductive surface and the electrolyte solution.
  • the present technology provides applying an electrical potential having a constant current density of 40 mA/cm 2 for a period of time of 2 to 5 minutes. During this short period of time and at such an elevated current density, a high flux of ions rapidly moves toward the cathode and a plurality of discrete regions of a calcium phosphate phase are deposited on the electroconductive surface of the implant.
  • the present technology provides applying an electrical potential having a constant current density of 30 mA/cm 2 for a period of time of 10 minutes.
  • the present technology provides beginning with an electrolyte solution containing calcium and phosphate ions and leading to the predominant electrochemical deposition of highly desirable hydroxyapatite crystalline having needle-shaped morphology on the surface of an implant.
  • the hydroxyapatite is deposited as homogeneous and discrete island type regions.
  • the implant includes nano-scale texturing, it is not covered by a complete coating of an amorphous calcium phosphate phase, as it would be with conventional electrochemical deposition techniques.
  • the morphology of the hydroxyapatite crystals can be visually described as needle-like or needle-shaped, and in various embodiments having needles with dimensions of less than about 500 nm in length and less than about 60 nm in width, and in some embodiments less than about 30 nm in width.
  • Typical needle lengths may be from about 200 and about 300 nm in certain embodiments, or from about 90 and about 140 nm in other embodiments.
  • Electrochemical deposition of a calcium phosphate phase depends in part on the pH-dependent solubility of the calcium phosphate, which has been found to decrease with increasing pH. Using an electrochemical deposition process, one can control the pH at the cathode/electrolyte interface.
  • the pH of the electrolyte solution is maintained at from about 5 to about 7, using hydrochloric acid or ammonium hydroxide.
  • the electrolyte solution can be maintained slightly acidic, for example, at a level of from about 5 to about 6. This slightly acidic environment allows for the partial dissolution of the CPP to occur in equilibrium with the precipitation and deposition processes.
  • the present technology provides placing the implants in a bath containing the electrolyte solution and rotating the implants during application of the electrical potential.
  • the present technology also provides for larger scale processes for making a plurality of medical implants having discrete regions of a calcium phosphate phase deposited thereon. It is envisioned that the process can treat from 2 up to 70 or more implants at one time, depending upon the size and surface area of the implants, as well as the desired electrochemical deposition parameters, including the available power supply.
  • the process can include preparing an electrolyte solution comprising calcium ions and phosphate ions having a concentration ratio of calcium:phosphate of about 1.7:1 as previously described.
  • a plurality of implants is then placed into the electrolyte solution, or bath. Any debris on the implant surface may lead to uncoated areas. Accordingly, the implants can optionally be cleaned prior to the deposition process, for example using an appropriate ultrasonic type wash.
  • the electrolyte solution is provided in an inner bath container that is placed or disposed within an appropriate outer bath container.
  • the outer bath container can be provided with circulating water to maintain a consistent temperature of the inner bath, for example, at about ambient temperature or alternatively about 37°C.
  • Each implant comprises at least one area having an electroconductive surface which, in various embodiments, includes a metallic area or surface. These electroconductive surfaces are appropriately connected and used as the cathodes for cathodic polarization.
  • a constant electrical potential is applied between the cathodes and the electrolyte solution, wherein the electrical potential has a constant current density of 40 mA/cm 2 .
  • the electrical potential can be applied for a period of time of 2 to 5 minutes depending on the remaining deposition parameters and desired amount of hydroxyapatite deposition. In another embodiment, a current density of 30 mA/cm 2 is applied for 10 minutes.
  • the process includes electrochemically depositing a plurality of discrete regions of needle-shaped hydroxyapatite crystals onto the electroconductive surfaces.
  • the implants can be appropriately rotated during the application of electrical potential, depending on the amount of hydrogen bubbling that may occur.
  • the implants can be removed and sent to a rinsing station.
  • the implants can also be sent to an appropriate anodizing station.
  • Such an anodizing bath may be provided including deionized water, trisodium phosphate dodecahydrate, and di-potasium hydrogen phosphate at ambient temperature.
  • the electrochemical deposition process may be carried out by cathodic polarization in a number of successive, repeated process cycles.
  • a process cycle may include cathodic polarization in one or more successive steps, in certain embodiments during at least two discrete intervals of time, with identical or different (increased or decreased) constant current densities, and a rinsing and/or drying phase following thereon.
  • a disc of Ti6A14V having a radius of about 0.5 inches and a thickness of 0.25 inches is prepared with a smooth machine finish, cleaned in an ultrasonic bath, and rinsed with distilled water. The thickness portion is masked and the disc sample is placed into an electrolyte solution at ambient temperature including 150 ml each of a stock solution of CaCl 2 and NH 4 H 2 PO 4 in concentrations of 33 mM and 20 mM, respectively. Deionized water is added providing a 3 L total volume solution having a final concentration of 1.67 mM calcium ions and 1.0 mM phosphate ions. The pH is adjusted to 5.1 using hydrochloric acid.
  • electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 40 mA/cm 2 in order to provide a high flux of ions toward the cathode.
  • cathodic polarization is complete and the sample is removed and rinsed with deionized water.
  • Electron microscopic examination reveals a plurality of discrete but homogenous regions of CPP having needle like morphology as shown in Figure 1 . Further IR-spectroscopic investigations provide proof that the discrete crystalline mineral phase comprises hydroxyapatite.
  • a disc of Ti6A14V is prepared as in Example 1.
  • the disc sample is placed into an electrolyte solution at ambient temperature including 15 ml each of a stock solution of CaCl 2 and NH 4 H 2 PO 4 in concentrations of 33 mM and 20 mM, respectively.
  • Deionized water is added providing a 3 L total volume solution having a final concentration of 0.167 mM calcium ions and 0.1 mM phosphate ions.
  • the pH is adjusted to 6.4 using ammonium hydroxide.
  • electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 20mA/cm 2 in order to provide a high flux of ions toward the cathode.
  • cathodic polarization is complete and the sample is removed and rinsed with deionized water.
  • Electron microscopic examination reveals a plurality of discrete but homogenous regions of CPP having needle like morphology as shown in Figure 2 . Further IR-spectroscopic and X-ray diffraction investigations provide proof that the discrete crystalline mineral phase comprises hydroxyapatite.
  • a disc of Ti6A14V is prepared as in Example 1.
  • the disc sample is placed into an electrolyte solution at ambient temperature including 15 ml each of a stock solution of CaCl 2 and NH 4 H 2 PO 4 in concentrations of 33 mM and 20 mM, respectively.
  • Deionized water is added providing a 3 L total volume solution having a final concentration of 0.167 mM calcium ions and 0.1 mM phosphate ions.
  • the pH is adjusted to 6.4 using ammonium hydroxide.
  • electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 30mA/cm 2 in order to provide a high flux of ions toward the cathode.
  • cathodic polarization is complete and the sample is removed and rinsed with deionized water.
  • Electron microscopic examination reveals a plurality of discrete but homogenous regions of CPP having needle like morphology as shown in Figure 3 . Further IR-spectroscopic and X-ray diffraction investigations provide proof that the discrete crystalline mineral phase comprises hydroxyapatite.

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  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Materials Engineering (AREA)
  • Metallurgy (AREA)
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Claims (2)

  1. Procédé de dépôt électrochimique de régions discontinues discrètes d'un phosphate de calcium comprenant de l'hydroxyapatite sur une surface métallique d'un implant médical comprenant au moins une zone ayant une surface électroconductrice, la surface électroconductrice présentant au moins une région texturée à l'échelle nanoscopique,
    et dans lequel le dépôt électrochimique est effectué dans une cellule ou un bain d'électrolyse, dans laquelle ou lequel au moins la surface métallique de l'implant est polarisée cathodiquement,
    le procédé comprenant les étapes consistant à :
    a. mettre en contact au moins une partie de la surface électroconductrice de l'implant avec une solution électrolytique comprenant des ions calcium et des ions phosphate ayant des ions calcium à une concentration de 1,7 mM et des ions phosphate à une concentration de 1,0 mM, le pH de la solution électrolytique étant maintenu à 5-7 en utilisant de l'acide chlorhydrique ou de l'hydroxyde d'ammonium ; et
    b. appliquer un potentiel électrique entre la surface électroconductrice et la solution électrolytique, une densité de courant de 40 mA/cm2 étant appliquée pendant 2 à 5 min, formant ainsi une pluralité de régions discontinues discrètes du phosphate de calcium sur la surface électroconductrice, le phosphate de calcium comprenant une morphologie en aiguilles, et dans la mesure où l'implant inclut une texturation à échelle nanoscopique, il n'est pas couvert par une couche complète d'une phase de phosphate de calcium amorphe ; et
    c. rincer ou anodiser ensuite l'implant.
  2. Procédé de dépôt électrochimique de régions discontinues discrètes d'un phosphate de calcium comprenant de l'hydroxyapatite sur une surface métallique d'un implant médical comprenant au moins une zone ayant une surface électroconductrice, la surface électroconductrice présentant au moins une région texturée à l'échelle nanoscopique,
    et dans lequel le dépôt électrochimique est effectué dans une cellule ou un bain d'électrolyse, dans laquelle ou lequel au moins la surface métallique de l'implant est polarisée cathodiquement,
    le procédé comprenant les étapes consistant à :
    a. mettre en contact au moins une partie de la surface électroconductrice de l'implant avec une solution électrolytique, la solution électrolytique ayant un pH de 6, une concentration en ions calcium de 0,167 mM et une concentration en ions phosphate de 0,1 mM ; et
    b. appliquer un potentiel électrique entre la surface électroconductrice et la solution électrolytique, une densité de courant de 30 mA/cm2 étant appliquée pendant 10 min à température ambiante, formant ainsi une pluralité de régions discontinues discrètes du phosphate de calcium sur la surface électroconductrice, le phosphate de calcium comprenant une morphologie en aiguilles, et dans la mesure où l'implant inclut une texturation à échelle nanoscopique, il n'est pas couvert par une couche complète d'une phase de phosphate de calcium amorphe ; et
    c. rincer ou anodiser ensuite l'implant.
EP10773461.8A 2009-10-19 2010-10-19 Procédés de dépôt de régions individuelles d'hydroxyapatite sur des implants médicaux Active EP2491167B1 (fr)

Applications Claiming Priority (2)

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US12/581,483 US20110089041A1 (en) 2009-10-19 2009-10-19 Methods of depositing discrete hydroxyapatite regions on medical implants
PCT/US2010/053138 WO2011049915A2 (fr) 2009-10-19 2010-10-19 Procédés de dépôt de régions individuelles d'hydroxyapatite sur des implants médicaux

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EP2491167B1 true EP2491167B1 (fr) 2019-07-10

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US20110089041A1 (en) 2011-04-21
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WO2011049915A2 (fr) 2011-04-28

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