WO2004098436A2

WO2004098436A2 - Method for producing adherent coatings

Info

Publication number: WO2004098436A2
Application number: PCT/US2004/013613
Authority: WO
Inventors: Racquel Z. Legeros; John P. Legeros; Shujie Li
Original assignee: New York University NYU
Current assignee: New York University NYU
Priority date: 2003-05-01
Filing date: 2004-05-03
Publication date: 2004-11-18
Anticipated expiration: 2005-11-01
Also published as: US6974532B2; WO2004098436A3; US20050000819A1

Abstract

A method for forming a highly adherent coating of a desired calcium phosphate phase on titanium-based substrates for use as orthopedic and dental implants. The calcium phosphate phase coating is electrochemically deposited onto the substrate from a metastable calcium phosphate electrolyte solution using a modulated electrical potential under pH, temperature and electrolyte composition and concentration conditions favorable for forming the desired calcium phosphate.

Description

Method for Producing Adherent Coatings of Calcium Phosphate Phases on Titanium and Titanium Alloy Substrates By Electrochemical Deposition

Field of The Invention

This invention relates generally to calcium phosphate materials for use in dental and

orthopedic applications and more specifically relates to an electrochemical method for

depositing coatings of calcium phosphate phases on titanium or titanium alloy substrates.

Background of The Invention

Calcium phosphate (Ca-P) materials commercially available as bone graft or bone

substitute materials for dental and orthopedic applications include calcium phosphate phases

such as: hydroxyapatite (HA), Ca₁₀(PO₄)₆(OH)₂. beta-tricalcium phosphate (β-TCP), Ca₃(P0₄)₂;

biphasic calcium phosphate (BCP) consisting of mixtures of HA and β-TCP; unsintered apatite

or calcium-deficient apatite (CDA); coralline HA, and bovine bone derived apatite (sintered

and unsintered). These materials are characterized as bioactive, osteoconductive, and

promote direct attachment with bone without intervening fibrous tissues, thus developing a very

strong interface between the Ca-P material and bone. However, a serious shortcoming of Ca-P

materials is their low mechanical or fracture strength and they therefore cannot be used in

load-bearing areas.

Commercially pure titanium (cp-Ti) and titanium (Ti) alloy (Ti6AI4V) are metals

possessing corrosion resistance, biocompatibility, durability, and strength. These metals are

preferred for dental and orthopedic implants or prosthesis. However, these metals do not

directly bond to the bone. 'HA-coated' dental and orthopedic implants were therefore developed to combine the bioactivity and osteoconductivity of the 'HA' coating and the

properties (e.g., strength) of the Ti or Ti alloy substrate. Plasma spraying is the coating

deposition technique used for the commercial 'HA-coated' orthopedic and dental implants. This

technique uses HA as the coating source and involves extremely high temperature. The high

temperature and other operating parameters produce coatings of variable composition,

principally in the ratio of the crystalline (principally HA) to non-crystalline (amorphous calcium

phosphate, ACP) phases (HA/ACP ratio). This ratio was found to vary from 30HA/70ACP to

70HA/30ACP in coatings of commercial implants. Of the crystalline phase, 90 to 95% is HA

and 5 to 10% is made up of mixtures of tricalcium phosphates (α-TCP, β-TCP), tetracalcium

phosphate (TTCP), and sometimes, calcium oxide, CaO. The coating composition (mainly the

HA/ACP ratio) significantly affects in vitro dissolution properties of the coating: the lower the

ratio, the more soluble the coating. The variability in coating degradation may affect biological

performance, coating stability and implant stability. It is therefore necessary to develop

alternative coating methods using low temperature that will provide coatings with reproducible

homogeneous composition.

Deposition of brushite or dicalcium phosphate dihydrate (DCPD), CaHP0₄.2H₂0,

dicalcium phosphate anhydrous (DCPA) or monetite, CaHP0₄, and apatite (AP) has been

achieved using electrochemical deposition method' AP coatings have also been obtained by

transformation of the initially formed DCPD or DCPA coating. In studies relating to these,

neither the adherence of the ECD-deposited calcium phosphate coating to the substrate nor

the dissolution properties of the coatings was reported.

Octacalciumphosphate (OCP), Ca₈H₂(P0₄)₆-5H₂0, one of the biologically relevant

calcium phosphates, can easily transform to carbonate hydroxyapatite (CHA) in synthetic

systems. Because of structural similarity between OCP and HA, Ca₁₀(PO₄) ₆(OH)₂, OCP is

speculated to be a necessary precursor of bone apatite which is a carbonate hydroxyapatite (CHA). OCP has been demonstrated to be more resorbable and to enhance more bone

formation than either HA or β-TCP.

SUMMARY OF THE INVENTION

Now in accordance with the present invention, an electrochemical method is provided

for depositing adherent octacalciumphosphate (OCP) and other coatings of calcium phosphate

phases on commercially pure titanium or titanium alloy (e.g. Ti6AI4V) substrates of different

shapes and different surface preparations. Calcium phosphate phases that can be

electrochemically deposited include: amorphous calcium phosphate, ACP (of different

compositions - including incorporation of Zn, Mg, F, P₂0₇, organic moieties, etc); dicalcium

phosphate dihydrate, DCPD, CaHP0₄.2H₂0; dicalcium phosphate anhydrous, DCPA, CaHP0₄;

octacalcium phosphate, OCP, Ca₈H₂(P0₄)₆.5H₂0; substituted tricalcium phosphate, b-TCP

(substituted with Mg, Zn, etc); calcium-deficient apatite, HAp (of different calcium deficiency);

biphasic calcium phosphate, BCP, consisting of mixture of HAp and substituted b-TCP of

varying HAp/b-TCP ratios; substituted apatites: carbonate hydroxyapatite, CHA; fluoroapatite,

FA, carbonate and F-substituted apatites, CFA; chloro-apatite, CIAp or (CI.OH)-Ap; Strontium

apatite, SrAP or (Sr,Ca)AP. In addition other substituents may also be deposited (e.g., borate,

manganate, citrate, etc.)

In addition, originally deposited calcium phosphate phase can be transformed to other

calcium phosphate phases (e.g. ACP a DCPD or HAp or substituted HAp; DCPD or DCPA -a

substituted HAp or substituted b-TCP; OCP -> substituted HAp; etc). Bioactive molecules or

drugs can be incorporated in the electrochemically deposited calcium phosphate - allowing

their controlled release or delivery in vivo. Titanium (Ti) alloy plates, tensile bars with various types of surfaces (e.g., grit blasted

with apatitic abrasive, chemically textured, arc-deposited, and CoCr-beaded) and dissolution

cylinders are electrochemically coated using modulated pulse time electric fields which can be

programmed by a microprocessor. Modulated electrochemical deposition (MECD) is carried

out using pH and temperature conditions favorable for OCP or other calcium phase formation.

Coatings produced by the invention were characterized using x-ray diffraction, FTIR, scanning

electron microscopy, tensile strength tests and solubility tests. XRD and FTIR analyses

showed that pure uniform OCP coatings were produced on Ti6AI4V surfaces with coating to

substrate tensile strengths greater than 7000 psi. Coatings on Ti Arc-deposited surfaces,

chemically textured surfaces and CoCr beaded surfaces all gave tensile strengths ranging from

5000 psi to 7000 psi with no coating shadows in the crevices. Dissolution of OCP coating in

100ml of 0.1 M Tris Buffer solution was determined from the amount of calcium (Ca) released

onto the buffer which was 7.7 ± 1.0 ppm Ca at pH 7.3 after 4hr, and 22 ± 1.4 ppm Ca at pH 3

after 2hr. OCP crystal size can be controlled by the current density and relative pulse time

modulation. Thus, by use of the invention: (1) highly adherent calcium phosphate (e.g., OCP)

coating of uniform compositions (e.g., OCP) on Ti alloy substrates can be obtained at low

temperatures using MECD by optimizing pulse time modulation of the electric field, reaction

pH, temperature and electrolyte composition; and (2) OCP readily transforms to CHA when

exposed to SBF.

BRIEF DESCRIPTION OF DRAWINGS

In the drawings appended hereto:

Figure 1 is a graph depicting XRD patterns of several calcium phosphate phase coatings deposited by the method of the invention;

Figure 2 is a graph depicting FT-IR patterns of several calcium phosphate coatings deposited

by the method of the invention;

Figure 3 is a series of SEMs of different calcium phosphate phase coatings deposited by the

method of the invention.

Figure 4 is a graph depicting dissolution of an electrodeposited OCP coating under several

conditions;

Figure 5 is an FTIR of an OCP coating before and after transformation to CHA and under

several other specified conditions; and

Figure 6 depicts XRD profiles before and after transformation to CHA.

DESCRIPTION OF PREFERRED EMBODIMENTS

Sample Preparation

Three (3) types of Ti alloy (Ti6AI4V) substrates and Ti alloy bars with four (4) different

surface preparations were used to demonstrate the invention. The three types were: plain Ti

alloy plate, 25 x 25 x 1.5mm³, tensile strength bars, diameter, 25 mm, length 42 mm and

dissolution cylinders, diameter, 12mm, length 25mm. The four kinds of surface preparations

were: grit blasted with an apatitic abrasive (MCD abrasive, HiMed, Bethpage); arc-deposited;

chemically textured and coated with Co-Cr beads. The plates and dissolution cylinders were

grit blasted with apatitic abrasive. The arc-deposited, chemically textured and Co-Cr beaded

surfaces were received from Stryker-Howmedica-Osteonics. Arc-deposited means that the Ti

coating was deposited by melting Ti wire with an electric arc (high voltage/high current) onto

the surface. Chemical treatment was by acid-etching. Co-Cr beaded surfaces were obtained by

bonding Co-Cr beads (425-500 microns in diameter) onto a Co-Cr substrate. Twelve (12) samples of each type of surface (grit-blasted with apatitic abrasive, arc-deposited, and coated

with Co-Cr beads) and six (6) samples of chemically textured surfaces were coated with OCP

for tensile-strength measurements. Twelve (12) grit-blasted OCP-coated cylinders were used

for dissolution studies, using six (6) cylinders for each pH (pH 3.0 and pH 7.4). The coating on

plates were used for analyses using scanning electron microscopy (SEM), x-ray diffraction

(XRD), Fourier transform infrared (FTIR) spectroscopy and inductive coupled plasma (ICP) for

elemental analyses and for transformation experiments in simulated body fluid (SBF). Coated

tensile bars were used for tensile measurements.

All substrates were cleaned ultrasonically, acid etched for 30 minutes, rinsed and

dried. Nail vanish was applied on the substrates except for a circular area (diameter, 1 ,0cm) at

the center. Two similar substrates were used as anode and cathode; the separation distance

was kept constant. MECD was carried out using modulated pulse time electric fields

programmed with a custom-made dual microprocessor. The pH and temperature conditions for

OCP formation were according to methods previously described (LeGeros, R.Z., et al. (1989)

Scan Electron Micro. 3:129-138, LeGeros R.Z., et al. (1991) Monographs in Oral Sciences 15:,

LeGeros, R.Z., et al. (1984) Scan Electron Micros 4:1771-1777 and LeGeros, R.Z. (1985)

Calcif Tissue Int. 37:194-197). Metastable calcium phosphate solutions for coating were

prepared by mixing 100ml 0.01 M Ca(Ac)₂ and 100ml 0.0067M NaH₂P0₄ solutions,

(Metastable calcium phosphate solutions can be used at different pH and temperature

conditions and electrolyte concentration to obtain the desired calcium phosphate). See R.Z.

LeGeros, 1991 , Calcium Phosphates in Oral Biology and Medicine. Monographs in Oral

Sciences. Vol. 15, H. Meyers, ed; Karger, Basel). The electrochemical deposition solution can

be at temperatures from room temperature to about 95°C. The present pH used depend on

the desired calcium phosphate phase and generally will be in the range of 4 to 12. The solution composition depends on the calcium phosphate phase desired or desired substitution

in the HAp or b-TCP.

The pH of each electrolyte was adjusted to 5.0 with HCI (0.1 M/L) using a combined pH

glass electrode at room temperature. After mixing and stirring, the pH of the solution was

adjusted again to 5.0 at 60°C. The solution temperature during the process was kept constant

in a water-bath maintained at 60°C, MECD deposition was performed under controlled pulse

current time and average current density of 4ma/cm² for 30 minutes, Preliminary experiments

were first performed to determine the effect of varying the nature of the modulation on OCP

crystal size. These experiments showed that OCP crystals as large as 5μm are obtained when

using a deposition program giving an "ON" pulse (potential applied) of 20 sec followed by an

"OFF" pulse of 40 sec; or OCP crystals smaller then 2μm, are obtained using a deposition

program giving an "ON" pulse of 5 sec followed by an "OFF" pulse of 5 sec. After the coating

process, coated samples were washed with distilled and deionized water and air-dried.

Characterization of the OCP coatings

Coating thickness was measured using a microscopic focusing technique.

The coatings were scraped from some plate substrates and powdered (< 90 microns)

before FTIR, XRD and ICP analyses.

FTIR analyses were made on a Nicolet 550 Series II. Micro-pellets were prepared by

mixing 1.0 mg of the scraped powdered coating with 300mg KBr (IR grade, Perkin-Elmer,

Connecticut) pressed under 10,000 psi.

XRD analyses were made on Philips APD 3520 using curved crystal monochromator

and Cu radiation generated at 45kV and 50 mA and using Arkansas quartz as standard. The

scraped powdered coating was placed on a quartz plate to reduce background radiation and

improve the signal to noise ratio. For X-ray microcamera, the powdered coating was dispersed as a thin film on a piece of scotch tape. The scotch tape was loaded in microcamera, the

dental negative film was exposed for 2 hours and developed.

Scanning electron microscopy (SEM) analyses were made using JEOL 5400 operating

at 20 KV. The coated plates were mounted on aluminum holder and coated with platinum.

For analyses of calcium and phosphate ion concentrations of the coating, ICP

analyses were made on Thermal-Electron Incorporated apparatus (Franklin, Mass). 1mg of

powdered coating was dissolved using a few drops of 17% HCI and diluted to 25 ml in a

volumetric flask using an acidic mixture solution (5% HCI and 2% HN0₃). Standard calcium and

phosphate solutions were prepared by diluting standard calcium and phosphate solutions

(Fischer Scientific, New Jersey) with the same acidic mixture solution.

Tensile bond strength determination

The tensile strength measurements were made using the facilities at Stryker-

Howmedica-Osteonics laboratories in New Jersey in accordance with ASTM specifications

("Specifications for calcium phosphate coating for implantable materials"). Specimen geometry

and test procedures complied with Osteonics Mechanical Test Procedure MTP002 (ASTM

F1501) using one layer (0.010 in.) of FM 1000® sheet adhesive (American Cyanamid. Wayne,

NJ) was utilized to bond specimen/grit-blasted mating plug on the coatings, The cure cycle for

all specimens was 180°C± 5° for 90 minutes. After cooling, the excess adhesive was removed

by lightly melting.

An Instron Model 4505 Universal Testing System under Series IX computer control

was employed for testing. The crosshead displacement rate was 0.05 in./min. Gross visual

observations and a stereoscope was used to determine the models of failure. Evaluation of the dissolution property of the coatings

Dissolution studies were made by suspending OCP-coated cylinders in 100ml of 0.1 M

Tris buffer solution (37°C), stirring rate 150 rpm, for 4 hrs at pH 7.3 (n=6) and 2hrs at pH 3

(n=6). A custom-made water bath accurate to ± 0.1 °C was part of the dissolution system. Six

(6) of cylinders were immersed in 100ml of 0.1 M Tris buffer solution for each pH (pH 3.0 and

pH 7.4), 37°C for 2 hours. Dissolution experiments performed at pH 3 reflect the acidic pH

environment of osteoclast cells while those performed at pH 7.3 reflect the normal

physiological pH. The calcium (Ca) ions released from the coating onto the buffer with time

was monitored using a Ca-ion selective electrode coupled with Metrohm 692 pH/lon Meter

connected to an IBM PS desktop computer. The dissolution procedure was in accordance with

ASTM F1926 specifications (Test method for evaluation of the environmental stability of

calcium phosphate coating').

Transformation of the OCP coating.

Six (6) coated plates were suspended in simulated body fluid at pH 7.25, 37°C for one

week. SBF solution was prepared according to Kokubo, T., (1996) Thermochim Acta,

280:479-490. Formation of carbonate hydroxyapatite was characterized using FTIR, XRD and

SEM.

RESULTS

Composition, crystallinity, morphology and thickness of the coatings.

The calcium phosphate phase coating was shown by FTIR (Figure 2 curve D), XRD

(Figure 1 , curve D) to consist of only OCP. (The Figures also show the patterns for additional

calcium phosphate coatings that can be deposited by the present invention by use of suitable

pH and temperature conditions and electrolyte concentration). XRD microcamera film showed a small diffraction ring (100) near the center, the strongest diffraction peak for OCP at 4.8°2Θ.

ICP analyses showed the Ca/P ratio of 1.33+0.05 further confirming the coating composition

(Ca/P of pure OCP = 1.33). The coating was shown by SEM to be composed of thin platy

crystals (Figure 3D). The crystal size of OCP was influenced by the parameters of current

density, pulse time modulation and pulse time frequency: the lower the current density, the

larger the crystal size and the shorter the pulse time frequency, the smaller the crystal size.

The average coating thickness on various types of surfaces was 19 microns. The coating

thickness on the four kinds of surface was not significantly different (Anova test, p<0.05).

Coating thickness can be increased by increasing the time of deposition.

Tensile strength of OCP coatings

The coatings on the surface grit-blasted with apatitic abrasive (n=12), chemically

textured (n=6), arc-deposited (n=12) and CoCr-beaded-surfaces (n=12), are all different.

Tensile strength of the coatiηg on various types of surfaces ranged from 5,000 to 7,000 psi

(35 MPa to 52 MPa). The tensile strengths of the coating on these four kinds of surfaces as a

group were significantly different from each other (Anova test, p <0.01). The tensile strength on

arc-deposited, CoCr-beaded surfaces and chemically textured surfaces were not significantly

different from each other (student t-test, p>0.05). The mean tensile strength of the surface grit

blasted with apatitic abrasive was found to be significantly higher than those from the arc-

deposited, CoCr-beaded and chemically textured surfaces (0.05>p>0.002).

Dissolution property of the coatings

The mean calcium concentration (ppm Ca) was 7.7 ± 1 ppm at pH: 7.3 after four hours

(A in Figure 4) and 22 ± 1.4 ppm at pH 3 (B in Figure 4) after two hours. Transformation of OCP coating in SBF

The OCP coating (Curve A in Figure 5) was transformed to CHA after immersion in

SBF as shown by FTIR (Curve B in Figure 5. Curve C shows the FTIR spectrum of cowbone

for comparison). Crystallinity (reflecting crystal size and/or perfection) is shown by the XRD

before and after transformation to CHA profiles (curves A and B in Figure 6) to be similar to

that of cowbone apatite (Curve C in Figure 6). SEM showed differences in morphology and

size of the coating crystals before and after exposure to SBF.

DISCUSSION

Plasma-sprayed HA coating has been shown to enhance bone apposition and

interfacial strength compared with uncoated Ti or Ti alloy dental and orthopedic implants.

However, the plasma-spray process, being a line-of-sight process, is not suitable for coating

porous surfaces and implants of complex geometry. Furthermore, because this process

involves very high temperatures, coating composition (principally, HA/ACP ratio) can vary

between coating layers (e.g., closest to and farthest from the metal substrate). Because of the

preferential dissolution of the ACP component, the variation in the HA/ACP may affect

biodegradation and stability of the coating and, ultimately, the stability of the implant.

In use of the modulated electrochemical deposition for Ca-P phases on the Ti alloy,

cathodic polarization of Ti alloy leads to an increase in pH at the interface between the alloy

and electrolyte due to the formation of OH^" ions. The sudden increase in pH triggers crystal

nucleation and initiates crystal growth of the desired calcium phosphate phase directly on the

substrate surface. OCP crystal size can be controlled by current density and relative pulse time

modulation. Crystals grown at high current density were smaller than those obtained at low

current density indicating that more ions had much higher probability of interacting with each other and forming larger number of nuclei sites at high current density. The crystal size was

also related to the duration of the pulse current: the longer the duration, the larger the crystal

size. Appropriate modulation of pulse current time allows the slower phosphate ions (H₂P0₄ ^"'

HP0₄ ^2", P0₄ ^3") to catch up and join faster calcium ions (Ca²⁺) to form Ca-P0₄ nuclei that will

eventually grow to OCP crystal.

By use of the invention, uniform OCP deposition was made on Ti alloy surfaces

regardless of shapes (plates or cylinders) or surface preparation (grit blasted with apatitic

abrasive, arc-deposited, chemically treated or Co-Cr beaded). Coatings consisting of desired

calcium phosphate phases (e.g., DCPD, DCPA, calcium deficient apatites, (F,OH)-apatite or

carbonatehydroxyapatite) can be obtained using the right combination of pH, temperature and

solution composition,

Tensile strength

Prior reported studies on electrodeposition of calcium phosphates (e.g. brushite,

monetite, apatite) have not included information on the tensile strength between the coating

and the metal substrate. We have found, using an Instron Universal testing system, that by

employing the present invention the tensile strengths of the OCP coating on different surfaces

ranged from 5000 psi to 7000 psi (35 MPa to 50 MPa). The tensile strength measurements

were made on OCP coating before immersion in SBF. The tensile strength value was highest

for the OCP coated on surface roughened by grit blasting with apatitic abrasive. Since the

microporosities of the OCP coatings on surfaces receiving different treatments were similar,

the observed higher tensile strength on surfaces grit blasted with apatitic abrasive cannot be

attributed to the possible contribution of the glue used. Instead, it may be due to the difference

in surface roughness introduced by the different treatments (grit blasting with alumina, acid

treatment, arc deposited Ti or Co-Cr beaded). Dissolution properties of OCP coatings

In vivo studies on calcium phosphate coated (plasma-sprayed 'HA') implants indicated

the importance of initial coating properties on the implant fixation and bone apposition. Dalton

and Cook (Dalton, J.E. et al. (1995) J Biomed Materials, 29:239-245) have shown that

degradation of some HA-coated implants resulted in less bone apposition than stable HA

coatings. (Nagano, M. et al, (1996) Biomaterials, 17:1771-1777) found that when an

amorphous coating dissolved, bone directly apposed underlying material. Initial studies on in

vitro dissolution of plasma-sprayed 'HA' coatings showed that variability in the dissolution

properties paralleled the variability in the coating composition, principally the HA/ACP ratio.

ASTM testing of properties of plasma-sprayed HA coatings include in vitro dissolution in

neutral and acidic solutions. In this study, neutral pH (7.4) represented normal physiological pH

and acidic pH (3) represented the pH of the environment during osteoclast-mediated activity on

the coatings.

The optimal biodegradation characteristics of calcium phosphate coatings are yet to be

resolved. A coating that is too soluble can degrade before enhanced stability is gained from

the calcium phosphate activity. Stable coatings, which are not readily resorbed or biodegraded,

are not as bioactive as the more degradable coatings. Additionally, the less stable coatings

(e.g., plasma-sprayed HA coatings with low HA/ACP ratio) may eventually delaminate and

separate from the underlying metallic structure. A coating with some intermediate degradation

response may be optimal for implant fixation.

Application of the method of invention showed low variance standard variation in the

dissolution data of the ECD deposited OCP coating indicating homogeneous and consistent

coating composition. This is a decided advantage compared to the variability in the

composition (mainly HA/ACP ratio) of the plasma-sprayed 'HA' coating. CONCLUSION

Modulated electrochemical deposition (MECD) is an alternative method to plasma-

spray technique for coating calcium phosphate on the metal alloy at low temperature. The

MECD method consists of depositing calcium phosphate coatings on implant surfaces by

immersion in an aqueous electrolyte containing Ca and P ions under modulated controlled

potential and current at low temperature (<100°C). This method has the following advantages

over high temperature techniques: (a) provides a more uniform and predictable coating

composition onto implants of complex geometry or porosity; (b) does not cause any adverse

heat effects on the substrates; (c) co-precipitation of bioactive molecules of growth factors can

be made if desired. Highly adherent, calcium phosphate coatings on Ti alloy substrates can be

obtained at low temperature using the MECD method by optimizing pulse time modulation of

the electric field and using appropriate reaction pH, temperature and electrolyte composition.

The MECD deposited OCP coatings show homogenous morphology, composition, thickness

and dissolution properties.

While the present invention has been described in terms of specific embodiments

thereof, it will be understood in view of the present disclosure, that numerous variations upon

the invention are now enabled to those skilled in the art, which variations yet reside within the

scope of the present teaching. Accordingly, the invention is to be broadly construed, and

limited only by the scope and spirit of the claims now appended hereto.

Claims

1. A method for forming a highly adherent coating of a desired calcium phosphate phase on a

titanium-based substrate for use as an orthopedic or dental implant, comprising:

electrochemically depositing the coating of said calcium phosphate phase onto said

substrate from a metastable calcium phosphate electrolyte solution using a modulated

electrical potential under pH, temperature and electrolyte composition and concentration

conditions favorable for forming the desired calcium phosphate phase.

2. A method in accordance with claim 1 , wherein said substrate is an alloy of titanium.

3. A method in accordance with claim 1 , wherein said substrate is substantially pure titanium.

4. A method in accordance with claim 1 , wherein said modulated electrical potential provides

pulses of plating current.

5. A method in accordance with claim 4, wherein said calcium phosphate phase comprises

octacalcium phosphate.

6. A method in accordance with claim 4, wherein said calcium phosphate phase comprises a

carbonate-substituted apatite,

7. A method in accordance with claim 4, wherein said calcium phosphate phase comprises a

calcium deficient apatite.

8. A method in accordance with claim 4, wherein said calcium phosphate phase comprises a

fluoride-substituted apatite,

9. A method in accordance with claim 4, wherein the crystal size of the calcium phosphate

phase deposit is controlled by one or both of the duration of the current pulses and of the

plating current density.

10. A titanium-based substrate for use as a dental or orthopedic implant, produced by the

method of claim 1.