EP2491167A2

EP2491167A2 - Methods of depositing discrete hydroxyapatite regions on medical implants

Info

Publication number: EP2491167A2
Application number: EP10773461A
Authority: EP
Inventors: Gautam Gupta; Andreas Sewing
Original assignee: Biomet Manufacturing LLC
Current assignee: Biomet Manufacturing LLC
Priority date: 2009-10-19
Filing date: 2010-10-19
Publication date: 2012-08-29
Anticipated expiration: 2030-10-19
Also published as: WO2011049915A2; WO2011049915A3; US20110089041A1; EP2491167B1

Abstract

A method for electrochemically depositing discrete regions of calcium phosphate onto a medical implant. The method includes providing an implant including at least one area having a metallic surface. At least a portion of the metallic surface is contacted with an electrolyte solution comprising calcium ions and phosphate ions. The metallic surface is used as a cathode, and an electrical potential is applied between the cathode and the electrolyte solution. The electrical potential is applied with a constant current density of from about 10 to about 50 mA/cm² for a period of time of from about 1 to about 20 minutes. A plurality of discrete regions of needle-shaped hydroxyapatite crystals are electrochemically deposited onto the metallic surface.

Description

METHODS OF DEPOSITING DISCRETE HYDROXY APATITE REGIONS

ON MEDICAL IMPLANTS

INTRODUCTION

[0001] The present technology relates to medical implants having discrete regions of a calcium phosphate (e.g., hydroxyapatite), and methods of their manufacture. In the growing field of medical devices, there is a continued need to provide lightweight orthopedic implants having enhanced in-growth capability. It is known that the time between in-growth of a metallic implant until the full mechanical loadability is achieved can be reduced if the implant has been coated with a calcium phosphate phase (CPP), such as hydroxyapatite.

[0002] Hydroxyapatite is a biocompatible material similar in composition to the mineral content of natural bone. As a result, 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. SUMMARY

[0003] The present technology provides methods for electrochemically depositing one or more discrete regions of a calcium phosphate onto a medical implant. In various embodiments, 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. [0004] In some embodiments, the method for electrochemically depositing discrete regions of a calcium phosphate phase onto a medical implant includes providing an implant including at least one area having a metallic surface. At least a portion of the metallic surface is contacted with an electrolyte solution comprising calcium ions and phosphate ions. The metallic surface is used as a cathode, and an electrical potential is applied between the cathode and the electrolyte solution. The electrical potential is applied with a constant current density of from about 10 to about 50 mA/cm for a period of time of between about 1 to about 20 minutes. A plurality of discrete regions of needle-shaped hydroxyapatite crystals is electrochemically deposited onto the metallic surface.

[0005] The present technology also provides processes for making a plurality of medical implants having discrete regions of calcium phosphate phase is provided. Such processes include preparing an electrolyte solution comprising calcium ions and phosphate ions having a concentration ratio of calcium:phosphate of about 1.7: 1. A plurality of implants is placed into the electrolyte solution, wherein each implant comprises at least one area having an electroconductive surface. The electroconductive surfaces are used as cathodes and an electrical potential is applied between the cathodes and the electrolyte solution, wherein the electrical potential has a constant current density of from about 10 to about 50 mA/cm . The electrical potential can be applied for a period of time of between about 1 to about 20 minutes. The process includes electrochemically depositing a plurality of discrete regions of needle-shaped hydroxyapatite crystals onto the electroconductive surfaces.

DRAWINGS

[0006] Figure 1 is a SEM micrograph magnified about 80,000x illustrating discrete regions of hydroxyapatite deposited on a titanium substrate and having a needlelike morphology; and

[0007] Figures 2 and 3 are SEM micrographs magnified about 10,000x illustrating discrete regions of hydroxyapatite deposited on a titanium substrate having a needle-like morphology.

[0008] It should be noted that the figures set forth herein are intended to exemplify the general characteristics of materials, methods and devices among those of the present technology, for the purpose of the description of certain embodiments. These figures may not precisely reflect the characteristics of any given embodiment, and are not necessarily intended to define or limit specific embodiments within the scope of this technology.

DETAILED DESCRIPTION

[0009] The following description of technology is merely exemplary in nature of the subject matter, manufacture and use of one or more inventions, and is not intended to limit the scope, application, or uses of any specific invention claimed in this application or in such other applications as may be filed claiming priority to this application, or patents issuing therefrom.

[0010] The headings (such as "Introduction" and "Summary") and subheadings used herein are intended only for general organization of topics within the present disclosure, and are not intended to limit the disclosure of the technology or any aspect thereof. In particular, subject matter disclosed in the "Introduction" may include novel technology and may not constitute a recitation of prior art. Subject matter disclosed in the "Summary" is not an exhaustive or complete disclosure of the entire scope of the technology or any embodiments thereof. Classification or discussion of a material within a section of this specification as having a particular utility is made for convenience, and no inference should be drawn that the material must necessarily or solely function in accordance with its classification herein when it is used in any given composition.

[0011] The description and specific examples, while indicating embodiments of the technology, are intended for purposes of illustration only and are not intended to limit the scope of the technology. Moreover, recitation of multiple embodiments having stated features is not intended to exclude other embodiments having additional features, or other embodiments incorporating different combinations of the stated features. Specific examples are provided for illustrative purposes of how to make and use the compositions and methods of this technology and, unless explicitly stated otherwise, are not intended to be a representation that given embodiments of this technology have, or have not, been made or tested. [0012] As used herein, the words "desirable", "preferred" and "preferably" refer to embodiments of the technology that afford certain benefits, under certain circumstances. However, other embodiments may also be preferred or desirable, under the same or other 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.

[0013] As used herein, 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. Similarly, 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.

[0014] Although the open-ended term "comprising," as a synonym of non- restrictive terms such as including, containing, or having, is used herein to describe and claim embodiments of the present technology, embodiments may alternatively be described using more limiting terms such as "consisting of or "consisting essentially of." Thus, for any given embodiment reciting materials, components or process steps, the present technology also specifically includes embodiments consisting of, or consisting essentially of, such materials, components or processes excluding additional materials, components or processes (for consisting of) and excluding additional materials, components or processes affecting the significant properties of the embodiment (for consisting essentially of), even though such additional materials, components or processes are not explicitly recited in this application. For example, recitation of a composition or process reciting elements A, B and C 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.

[0015] As referred to herein, all 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. It is envisioned that two or more specific exemplified values for a given parameter may define endpoints for a range of values that may be claimed for the parameter. For example, if Parameter X is exemplified herein to have value A and also exemplified to have value Z, it is envisioned that Parameter X may have a range of values from about A to about Z. Similarly, it is envisioned that disclosure of two or more ranges of values for a parameter (whether such ranges are nested, overlapping or distinct) subsume all possible combination of ranges for the value that might be claimed using endpoints of the disclosed ranges. For example, if Parameter X is exemplified herein to have values in the range of 1 - 10, or 2 - 9, or 3 - 8, it is also envisioned that Parameter X may have other ranges of values including 1 - 9, 1 - 8, 1 - 3, 1 - 2, 2 - 10, 2 - 8, 2 - 3, 3 - 10, and 3 - 9.

[0016] When an element or layer is referred to as being "on", "engaged to", "connected to" or "coupled to" another element or layer, it may be directly on, engaged, connected or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being "directly on", "directly engaged to", "directly connected to" or "directly coupled to" another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," etc.). As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

[0017] The present technology provides methods for electrochemically depositing discrete 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. At the same time, efforts continue to be made to improve bioinert behavior of implant materials. Calcium phosphate phases (CPP) have a lot of bioactive potential, thus enabling chemical bonding to natural bone. As used herein, the main inorganic constituent CPP may contain amorphous calcium phosphate (Ca₉(P0₄)6 · nH₂0), hydroxyapatite (Ca₁o(P0₄)6(OH)₂), octacalcium phosphate (CagH₂ (PO)₆H₂0), or brushite (CaHP0₄ · 2H₂0), or mixtures thereof. The CPP can additionally be doped with ions such as fluoride, silver, magnesium, carbonate, strontium, or sodium.

[0018] As is known in the art, hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂) is a CPP biocompatible material that is similar in composition to the major inorganic mineral content of natural bone. As such, 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. For example, the high process temperatures may cause partial decomposition of hydroxyapatite, resulting in the formation of other CPP, including amorphous calcium phosphate (ACP), a-tricalcium phosphate (TCP), β-TCP, tetracalcium phosphate, and calcium oxide. Numerous studies have found that more mechanical failure occurs at the metal/hydroxyapatite interface, rather than at the bone/hydroxyapatite interface. Accordingly, electrochemical deposition techniques are advantageous.

[0019] One problem with the known deposition techniques is the time required in order to obtain a crystalline hydroxyapatite structure, having needle-like morphology, from an amorphous precursor that is formed and subsequently changed into a crystalline material, mimicking in vivo mineralization process. Typically, spheres begin to grow at energetically favored places, commonly identified as the "ACP phase." The ACP is then transformed to the crystalline phase of hydroxyapatite. For example, small calcium phosphate precursor island regions are first formed that coalesce and form a continuous, homogeneous pre-layer on the metal surface. Both the pre-layer and the spheres comprise clusters of Ca₃(P0₄)₂ from which preferential crystalline hydroxyapatite needles grow:

Ca₃(P0₄)₂ + Ca²⁺ + 2 OH→ Ca₁₀(PO₄)₆(OH)₂

[0020] While this two-phase process has many beneficial aspects, 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.

[0021] 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. In particular, in various embodiments, it provides a CPP deposition that is predominantly needle-shaped hydroxyapatite after only a short duration of time. For example, 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. In certain embodiments, it may be preferred that the hydroxyapatite has a random orientation.

[0022] In various embodiments of the present technology, a medical implant is provided 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 can be provided with nano-scale texturing, if desired. 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.

[0023] The electrochemical deposition can be carried out in an electrolysis cell, or bath, in which the implant, as least the metallic or otherwise electroconductive surface, is cathodically polarized. For example, 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.

[0024] At least a portion of the electroconductive surface is placed in contact with an electrolyte solution comprising calcium ions and phosphate ions. For example, the electrolyte can comprise a Ca²⁺/H_xP0₄ ^{(3 x)"} containing solution. In various embodiments, 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. In certain embodiments, 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). Of course it is also possible to choose a different concentration ratio of calcium and phosphate ions, if desired. In terms of actual concentration of the calcium and phosphate ions, various embodiments currently provide 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. Such a concentration may call for the electrical potential to be applied for from about 1 to about 5 minutes, preferably about 2.5 minutes, in order to obtain desired deposition. In other embodiments, it is possible to decrease the concentration to about 1/10^ώ, or less, of the standard-like concentration. For example, 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. For embodiments having lower concentrations, 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 can be applied for from about 1 to about 20 minutes, or from about 5 to about 15 minutes, such as 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. [0025] Once contact has been established between the electroconductive or metallic surface of the implant and the electrolyte solution, for example, by immersing the implant into an electrolyte bath, an electrical potential is applied between the electroconductive surface and the electrolyte solution. In various embodiments, the present technology provides applying an electrical potential having a constant current density of from about 10 to about 50 mA/cm for a period of time of from about 1 to about 20 minutes. For example, the electrical potential can be applied having a constant current density of from about 20 to about 40 mA/cm for a period of time of from about 2 to about 10 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. Without limiting the mechanism, function or utility of the present technology, it is believed that, in embodiments having the appropriate concentration levels, heterogeneous nucleation or precipitation may occur within the solution near the implant surface that additionally settles on the implant surface.

[0026] Specifically, 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. Thus, to the extent an implant includes any 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. As described herein, 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. Depending upon the various parameters, it may be possible to obtain a slightly mixed state of hydroxyapatite and amorphous calcium phosphate phase, provided that the electrochemical deposition still provides a homogeneous, discrete island-type coating regions. [0027] 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. As is known in the art, during cathodic polarization of a metal in an aqueous electrolyte, the following reactions occur at the surface of the cathode (reduction of water, proton discharge, and reduction of dissolved oxygen):

2 H₂0 + 2 e - -» H₂ + 2 OH

2 H₃0⁺ + 2 e - -» H₂ + 2 H₂0

0₂ + H₃0⁺ + 4 e - -» 3 OH

resulting in the formation of hydroxyl ions and hence alkalization close to the surface. In the case of a metal implant comprising titanium, the calcium and phosphate ions react with the hydroxyl groups on the titanium surface because of heterogeneous nucleation. Hydroxyl ions from the cathodic sub process (above) hydroxylate the titanium surface by physical and chemical adsorption:

Ti0₂ + H₂0 -> TiO(OH)₂

[0028] Additionally, it is known that increased cathodic polarization is associated with increased hydrogen production and oxygen depletion of the titanium surface because of the partial reduction of titanium dioxide:

Ti0₂ + 2H₂0 + e^" -> Ti(OH)₃ + OH^"

[0029] Thus in various embodiments, the pH of the electrolyte solution is maintained at from about 3 to about 7, or from about 5 to about 7, using hydrochloric acid or ammonium hydroxide. For some applications, it may be desirable to maintain the pH at the near physiological condition of about 6 (e.g., about 6.4). In certain other embodiments, because of the desire to avoid a continuous coating of CPP on the metal implant, 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.

[0030] While it is believed that the CPP deposition process is accelerated with increasing current density, the formation of CPP on a metal surface is generally controlled by a nucleation mechanism as the initial growth step. With increasing current density, however, hydrogen gas development is also increased. Accordingly, care must be taken into consideration because hydrogen bubbles may initiate a faster electrolyte exchange in front of the cathode and increase the diffusion of the electrolyte ions due to a thinner diffusion boundary layer. Excessive hydrogen bubbling may also interfere with the electrochemical deposition process and prevent homogeneous CPP formation. Accordingly, in various embodiments, the present technology provides placing the implants in a bath containing the electrolyte solution and rotating the implants during application of the electrical potential.

[0031] 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.

[0032] 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. In certain embodiments, 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 from about 10 to about 50 mA/cm . As previously discussed, the electrical potential can be applied for a period of time of from about 1 to about 20 minutes depending on the remaining deposition parameters and desired amount of hydroxyapatite deposition. 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. In various aspects, once the electrochemical deposition is complete, the implants can be removed and sent to a rinsing station. Depending on the particular metal used, 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.

[0033] In certain embodiments, the electrochemical deposition process may be carried out by cathodic polarization in a number of successive, repeated process cycles. For example, 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.

[0034] The present technology is further illustrated through the following non-limiting examples.

Example 1

[0035] 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 CaCl₂ and ΝΗ₄Η₂Ρ0₄ 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.

[0036] After connection to a potentiostat, electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 40 mA/cm in order to provide a high flux of ions toward the cathode. After a deposition time of about 2.5 minutes, the 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.

Example 2

[0037] 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 CaCl₂ and ΝΗ₄Η₂Ρ0₄ 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.

[0038] After connection to a potentiostat, electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 20mA/cm in order to provide a high flux of ions toward the cathode. After a deposition time of about 10 minutes, the 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.

Example 3

[0039] 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 CaCl₂ and NH₄H₂P0₄ 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.

[0040] After connection to a potentiostat, electrochemical deposition is carried out by means of galvanostatic polarization under cathodic current flow at a current density of about 30mA/cm in order to provide a high flux of ions toward the cathode. After a deposition time of about 10 minutes, the 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.

[0041] The embodiments described herein are exemplary and not intended to be limiting in describing the full scope of compositions and methods of the present technology. Equivalent changes, modifications and variations of embodiments, materials, compositions and methods can be made within the scope of the present technology, with substantially similar results.

Claims

CLAIMS What is claimed is:

1. A method for electrochemically depositing a discrete region of a calcium phosphate onto a medical implant comprising at least one area having an electroconductive surface, the method comprising:

a. contacting at least a portion of the electroconductive surface of the implant with an electrolyte solution comprising calcium ions and phosphate ions; and b. applying an electrical potential between the electroconductive surface and the electrolyte solution, thereby forming a plurality of discrete regions of a calcium phosphate onto the electroconductive surface, wherein the calcium phosphate comprises a needle-shaped morphology.

2. The method of Claim 1, wherein the applying an electrical potential comprises applying a constant current density of from about 10 to about 50 mA/cm for a period of time of from about 1 to about 20 minutes, wherein the calcium phosphate phase comprises hydroxyapatite.

3. The method of Claim 2, wherein the applying an electrical potential comprises applying a constant current density of about 40 mA/cm for a period of time of from about 2 to about 5 minutes.

4. The method of Claim 1, wherein the electrolyte solution comprises calcium chloride and ammonium dihydrogen phosphate in an amount that corresponds to a calcium:phosphate ion ratio of about 1.7: 1.

5. The method of Claim 4, wherein the concentration of calcium ions in the electrolyte solution is about 1.7 mM.

6. The method of Claim 1, wherein the electrolyte solution is maintained at a pH of from about 3 to about 7 using hydrochloric acid or ammonium hydroxide.

7. The method of Claim 1, wherein the contacting comprises placing the implant in a bath containing the electrolyte solution and rotating the implant during application of the electrical potential.

8. The method of Claim 1, wherein the electrolyte solution has a pH of about

5.1, a concentration of calcium ions of about 1.7 mM, and a concentration of phosphate ions of about 1.0 mM, and wherein the applying an electrical potential comprises applying a constant current density of about 40 mA/cm is provided for about 2 minutes at ambient temperature.

9. The method of Claim 1, wherein the electrolyte solution has a pH of about 6, a concentration of calcium ions of about 0.2 mM, and a concentration of phosphate ions of about 0.1 mM, and wherein the applying an electrical potential comprises applying a constant current density of about 30 mA/cm for about 10 minutes at ambient temperature.

10. The method of Claim 1, wherein the electroconductive surface of the implant comprises a material from the group consisting of titanium, a titanium alloy, titanium nitrate, a CoCrMo alloy, stainless steel, an electroconductive polymer, and mixtures thereof.

11. The method of Claim 1, wherein the electroconductive surface of the implant comprises nano- scale texturing.

12. A method for electrochemically depositing a discrete region of a calcium phosphate onto a medical implant comprising at least one area having a metallic surface, the method comprising:

a. contacting at least a portion of the metallic surface of the implant with an electrolyte solution comprising calcium ions and phosphate ions; and

b. applying an electrical potential between the metallic surface as a cathode and the electrolyte solution having a constant current density of from about 10 to about

50 mA/cm for a period of time of from about 1 to about 20 minutes, thereby depositing a plurality of discrete regions of needle-shaped hydroxyapatite crystals onto the metallic surface.

13. The method of Claim 12, further comprising allowing partial dissolution of the hydroxyapatite to occur concurrent with the depositing.

14. The method of Claim 13, wherein the electrolyte solution is maintained at a pH of from about 5 to about 7.

15. The method of Claim 12, wherein the applying the electrical potential comprises applying the electrical potential for at least two discrete intervals of time.

16. A process for making a plurality of medical implants having discrete regions of a calcium phosphate, comprising:

a. preparing an electrolyte solution comprising calcium ions and phosphate ions having a concentration ratio of calcium:phosphate of about 1.7: 1;

b. placing a plurality of implants into the electrolyte solution, wherein each implant comprises at least one area having an electroconductive surface; and

c. applying a constant electrical potential between the electroconductive surfaces as cathodes and the electrolyte solution, wherein the electrical potential has a constant current density of from about 10 to about 50 mA/cm and is applied for a period of time of from about 1 to about 20 minutes, thereby depositing a plurality of discrete regions of needle-shaped hydroxyapatite crystals onto the electroconductive surfaces.

17. The process of Claim 16, wherein the electrolyte solution is in an inner bath container that is disposed within an outer bath container, and the outer bath container contains circulating water maintained at a temperature of about 37 °C.

18. The process of Claim 16, further comprising removing the plurality of implants from the electrolyte solution after the depositing, rinsing the implants, and anodizing the implants.

19. The process of Claim 16, wherein the electrolyte solution comprises deionized water, calcium chloride dihydrate, and ammonium dihydrogen phosphate.

20. The process of Claim 16, further comprising cleaning the plurality of implants using an ultrasonic wash prior to placing the plurality of implants in the electrolyte solution.