Electrodeposition of Calcium Phosphate Coatings on Metallic Substrates for Bone Implant Applications: A Review

: This review summaries more than three decades of scientiﬁc knowledge on electrodeposition of calcium phosphate coatings. This low-temperature process aims to make the surface of metallic bone implants bioactive within a physiological environment. The ﬁrst part of the review describes the reaction mechanisms that lead to the synthesis of a bioactive coating. Electrodeposition occurs in three consecutive steps that involve electrochemical reactions, pH modiﬁcation, and precipitation of the calcium phosphate coating. However, the process also produces undesired dihydrogen bubbles during the deposition because of the reduction of water, the solvent of the electrolyte solution. To prevent the production of large amounts of dihydrogen bubbles, the current density value is limited during deposition. To circumvent this issue, the use of pulsed current has been proposed in recent years to replace the traditional direct current. Thanks to breaking times, dihydrogen bubbles can regularly escape from the surface of the implant, and the deposition of the calcium phosphate coating is less disturbed by the accumulation of bubbles. In addition, the pulsed current has a positive impact on the chemical composition, morphology, roughness, and mechanical properties of the electrodeposited calcium phosphate coating. Finally, the review describes one of the most interesting properties of electrodeposition, i.e., the possibility of adding ionic substituents to the calcium phosphate crystal lattice to improve the biological performance of the bone implant. Several cations and anions are reviewed from the scientiﬁc literature with a description of their biological impact on the physiological environment.


Introduction
The worldwide clinical demand for bone tissue repair increases every year, particularly due to the aging population [1][2][3][4]. The main metallic bone implants used in orthopedic or dental surgeries are titanium alloys [5][6][7][8][9][10], stainless steel [11][12][13][14][15], and CoCr alloys [16][17][18][19][20][21][22]. These alloys are used because they have suitable mechanical properties for bone tissue replacement and their biocompatibility with the body environment is good. According to the International Union of Pure and Applied Chemistry (IUPAC), biocompatibility is the ability of a material to be in contact with a biological system without producing an adverse effect [23][24][25]. Although these alloys are biocompatible with the body environment, their biological interaction with the bone tissues is very low. Without any improvement in the bioactivity of the implant surface, the bone anchor fails, and revision surgery is required. This is the reason why metal bone implants are commonly coated with calcium phosphate, a ceramic material with a chemical composition similar to that of bone mineral [26][27][28][29][30][31][32]. The bioactivity of the calcium phosphate surface layer stimulates the formation of a direct, adherent, and strong bond with bone tissue [33,34]. The calcium phosphate Electrodeposition uses electrical energy from a generator to trigger a series o ical reactions in an aqueous solution, leading to the synthesis of a calcium phosph ing on a conductive surface [85]. The direct current was typically used first for m twenty years but pulsed current electrodeposition has grown in recent years. T reason is that the pulsed current mode includes some break times during dep providing several benefits detailed in this review of the literature. The first se depth describes the reaction mechanisms involved during the electrodeposition The direct current and pulsed current modes are presented and compared in the fo sections. The last part presents more specific developments of electrodepositi some ionic additives to enhance the biological properties of the synthesized calciu phate coatings.

Electrodeposition of Calcium Phosphate Coatings
Electrodeposition is an electrochemical process that uses two electrodes imm an aqueous solution containing calcium and phosphate ions. Most experimental p use calcium nitrate tetrahydrate ((CaNO3)2·4H2O) and ammonium dihydrogen ph (NH4(H2PO4)) to produce the electrolyte solution. The two electrodes are connect electrical generator (Figure 2). Electrodeposition uses electrical energy from a generator to trigger a series of chemical reactions in an aqueous solution, leading to the synthesis of a calcium phosphate coating on a conductive surface [85]. The direct current was typically used first for more than twenty years but pulsed current electrodeposition has grown in recent years. The main reason is that the pulsed current mode includes some break times during deposition, providing several benefits detailed in this review of the literature. The first section in-depth describes the reaction mechanisms involved during the electrodeposition process. The direct current and pulsed current modes are presented and compared in the following sections. The last part presents more specific developments of electrodeposition with some ionic additives to enhance the biological properties of the synthesized calcium phosphate coatings.

Electrodeposition of Calcium Phosphate Coatings
Electrodeposition is an electrochemical process that uses two electrodes immersed in an aqueous solution containing calcium and phosphate ions. Most experimental protocols use calcium nitrate tetrahydrate ((CaNO 3 ) 2 ·4H 2 O) and ammonium dihydrogen phosphate (NH 4 (H 2 PO 4 )) to produce the electrolyte solution. The two electrodes are connected to an electrical generator ( Figure 2). In an electrolytic cell, the anode is the positive electrode, and the cathode is the negative electrode. When a current density is applied, the electrolysis of water (the solvent) triggers redox reactions on the surfaces of both electrodes. At the cathode where the metal bone implant is connected, the electrochemical reactions imply a pH variation that induces the surface precipitation of a calcium phosphate layer.

Electrochemical Reactions
Several redox reactions may occur at the two electrode-electrolyte interfaces. Oxidation reactions take place at the anode, and reduction reactions take place at the cathode. The main redox reactions of the process involve water, the solution solvent whose anodic oxidation is: The cathodic reduction of water occurs simultaneously: In an acidic medium, proton reduction can also take place at the cathode: These reduction reactions locally increase the pH value of the solution at the cathodeelectrolyte interface, causing acid-base reactions. However, several authors also describe other electrochemical reactions that affect the local pH value in the vicinity of the cathode [69,[96][97][98]: In an electrolytic cell, the anode is the positive electrode, and the cathode is the negative electrode. When a current density is applied, the electrolysis of water (the solvent) triggers redox reactions on the surfaces of both electrodes. At the cathode where the metal bone implant is connected, the electrochemical reactions imply a pH variation that induces the surface precipitation of a calcium phosphate layer.

Electrochemical Reactions
Several redox reactions may occur at the two electrode-electrolyte interfaces. Oxidation reactions take place at the anode, and reduction reactions take place at the cathode. The main redox reactions of the process involve water, the solution solvent whose anodic oxidation is: The cathodic reduction of water occurs simultaneously: In an acidic medium, proton reduction can also take place at the cathode: These reduction reactions locally increase the pH value of the solution at the cathodeelectrolyte interface, causing acid-base reactions. However, several authors also describe other electrochemical reactions that affect the local pH value in the vicinity of the cathode [69,[96][97][98]: However, the amounts of oxygen, nitrate, and dihydrogen phosphate ions are very low compared to the amount of water, the solvent of the electrolyte solution. The reduction of water or the reduction of protons are the main cathodic reactions during the electrochemical process. The corresponding pH variations in the vicinity of the cathode promote the dissociation of the dihydrogen phosphate ions according to an acid-base process.

Acid-Base Reactions
As prepared, the pH of the electrolyte solution is typically acid (4 < pH < 5). At the cathode-electrolyte interface, the variation of pH due to the reduction of water induces the dissociation of dihydrogen phosphate ions in the solution ( Figure 3).
However, the amounts of oxygen, nitrate, and dihydrogen phosphate ions low compared to the amount of water, the solvent of the electrolyte solution. Th tion of water or the reduction of protons are the main cathodic reactions during trochemical process. The corresponding pH variations in the vicinity of the catho mote the dissociation of the dihydrogen phosphate ions according to an acid-base

Acid-Base Reactions
As prepared, the pH of the electrolyte solution is typically acid (4 < pH < 5 cathode-electrolyte interface, the variation of pH due to the reduction of water the dissociation of dihydrogen phosphate ions in the solution (Figure 3). The concentration of phosphate species as a function of the pH of the so shown in Figure 4. With a pH value between 4 and 5, the electrolytic solution initially contains d gen phosphate ions (H 2 PO 4 − ). When the local pH increases between 7.2 and 12 vicinity of the cathode, the hydrogen phosphate ions (HPO 4 2− ) become the major ph ions produced according to reaction (12): For pH values greater than 12.3, the phosphate ions (PO 4 3− ) predominate ac to reaction (13): The concentration of phosphate species as a function of the pH of the solution is shown in Figure 4.
However, the amounts of oxygen, nitrate, and dihydrogen phosphate ions a low compared to the amount of water, the solvent of the electrolyte solution. The tion of water or the reduction of protons are the main cathodic reactions during t trochemical process. The corresponding pH variations in the vicinity of the catho mote the dissociation of the dihydrogen phosphate ions according to an acid-base

Acid-Base Reactions
As prepared, the pH of the electrolyte solution is typically acid (4 < pH < 5) cathode-electrolyte interface, the variation of pH due to the reduction of water the dissociation of dihydrogen phosphate ions in the solution (Figure 3).  With a pH value between 4 and 5, the electrolytic solution initially contains d gen phosphate ions (H 2 PO 4 − ). When the local pH increases between 7.2 and 12. vicinity of the cathode, the hydrogen phosphate ions (HPO 4 2− ) become the major ph ions produced according to reaction (12): For pH values greater than 12.3, the phosphate ions (PO 4 3− ) predominate ac to reaction (13): With a pH value between 4 and 5, the electrolytic solution initially contains dihydrogen phosphate ions (H 2 PO − 4 ). When the local pH increases between 7.2 and 12.3 in the vicinity of the cathode, the hydrogen phosphate ions (HPO 2− 4 ) become the major phosphate ions produced according to reaction (12): Coatings 2022, 12, 539

Calcium Phosphate Coating Precipitation
Reactions (12) and (13) induce a local ionic supersaturation that causes the precipitation of a calcium phosphate coating characterized by low solubility and high thermodynamic stability. As a function of the pH value in the vicinity of the cathode, various phases can precipitate: dicalcium phosphate dihydrate (brushite): octacalcium phosphate: calcium-deficient apatite: with 0 < x < 2 -hydroxyapatite: The composition of the calcium phosphate coating depends on the pH value at the cathode, which is related to the current density imposed by the generator. The main characteristic of these calcium phosphate phases is their stoichiometry, specifically described in biomaterials science by their calcium to phosphorus atomic ratio (Ca/P). The stoichiometry of the phase is related to its solubility in a physiological environment, corresponding to the surface bioactivity conferred to the bone-implant (Table 1). Experimentally, the phases of calcium phosphate are mostly identified by X-ray diffraction ( Figure 5) and infrared spectroscopy ( Figure 6).  Thermal annealing of calcium-deficient apatite (Ca 10− (HPO 4 ) (PO 4 ) 6− (OH) 2− ) at 800 °C produces a mixture of crystalline phases whose proportions depend on its stoichiometry, hence its Ca/P atomic ratio. The obtained crystallized material is a biphasic compound.
If the value of x is between 0 and 1, the calcium-deficient apatite phase has a Ca/P atomic ratio between 1.5 and 1.67. Crystallization of calcium-deficient apatite produces a mixture of HAP and β-tricalcium phosphate (β-TCP) according to reaction (18).
If the value of x is exactly 1, the calcium to phosphorus atomic ratio is 1.5 and the calcium-deficient apatite phase is specifically named tricalcium phosphate (TCP). Thermal annealing at 800 °C crystallizes it into the β phase according to reaction (19) [113].   Thermal annealing of calcium-deficient apatite (Ca 10− (HPO 4 ) (PO 4 ) 6− (OH) 2− ) at 800 °C produces a mixture of crystalline phases whose proportions depend on its stoichiometry, hence its Ca/P atomic ratio. The obtained crystallized material is a biphasic compound.
If the value of x is between 0 and 1, the calcium-deficient apatite phase has a Ca/P atomic ratio between 1.5 and 1.67. Crystallization of calcium-deficient apatite produces a mixture of HAP and β-tricalcium phosphate (β-TCP) according to reaction (18).
If the value of x is exactly 1, the calcium to phosphorus atomic ratio is 1.5 and the calcium-deficient apatite phase is specifically named tricalcium phosphate (TCP). Thermal annealing at 800 °C crystallizes it into the β phase according to reaction (19) [113]. Thermal annealing of calcium-deficient apatite (Ca 10−x (HPO 4 ) x (PO 4 ) 6−x (OH) 2−x ) at 800 • C produces a mixture of crystalline phases whose proportions depend on its stoichiometry, hence its Ca/P atomic ratio. The obtained crystallized material is a biphasic compound.
If the value of x is between 0 and 1, the calcium-deficient apatite phase has a Ca/P atomic ratio between 1.5 and 1.67. Crystallization of calcium-deficient apatite produces a mixture of HAP and β-tricalcium phosphate (β-TCP) according to reaction (18). If the value of x is exactly 1, the calcium to phosphorus atomic ratio is 1.5 and the calcium-deficient apatite phase is specifically named tricalcium phosphate (TCP). Thermal annealing at 800 • C crystallizes it into the β phase according to reaction (19) [113]. TCP

β-TCP
The XRD pattern and the FT-IR spectrum of β-TCP are shown in Figures 7 and 8

Drawbacks of Direct Current Electrodeposition
Although electrodeposition is an efficient process to produce calcium phosphate coatings, there are several disadvantages and limitations to using it in a direct current mode.

Ionic Mobility
As described in Section 2.3, electrodeposited calcium phosphate coatings are obtained by precipitation of cations (Ca 2+ ) with anions (phosphates). Most of the protocols in the literature describe electrolytic solutions prepared with calcium salt and phosphate salt whose molar concentrations have a ratio of 1.67. Typically, the concentration of calcium salt is 0.042 mol L −1 and the concentration of phosphate salt is 0.025 mol L −1 . This

Drawbacks of Direct Current Electrodeposition
Although electrodeposition is an efficient process to produce calcium phosphate coatings, there are several disadvantages and limitations to using it in a direct current mode.

Ionic Mobility
As described in Section 2.3, electrodeposited calcium phosphate coatings are obtained by precipitation of cations (Ca 2+ ) with anions (phosphates). Most of the protocols in the literature describe electrolytic solutions prepared with calcium salt and phosphate salt whose molar concentrations have a ratio of 1.67. Typically, the concentration of calcium salt is 0.042 mol L −1 and the concentration of phosphate salt is 0.025 mol L −1 . This

Drawbacks of Direct Current Electrodeposition
Although electrodeposition is an efficient process to produce calcium phosphate coatings, there are several disadvantages and limitations to using it in a direct current mode.

Ionic Mobility
As described in Section 2.3, electrodeposited calcium phosphate coatings are obtained by precipitation of cations (Ca 2+ ) with anions (phosphates). Most of the protocols in the literature describe electrolytic solutions prepared with calcium salt and phosphate salt Coatings 2022, 12, 539 8 of 24 whose molar concentrations have a ratio of 1.67. Typically, the concentration of calcium salt is 0.042 mol L −1 and the concentration of phosphate salt is 0.025 mol L −1 . This molar ratio is generally chosen with the perspective to produce hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), the gold standard among calcium phosphates, whose calcium to phosphorus atomic ratio is 1.67. However, despite this molar ratio in solution, very few articles show electrodeposited calcium phosphate coatings with the stoichiometry of hydroxyapatite. This could be the result of the mobility of the ions in the solution that modifies the local concentrations of calcium and phosphate ions in the vicinity of the electrodes. During the electrochemical process, the ions move under the influence of the electric field between the two electrodes. The cations move toward the cathode, and the anions move toward the anode [116,117]. The longer the deposition, the more local concentrations in the solution are modified and impact the stoichiometry of the electrodeposited coating. This implies a limitation of the process duration when electrodeposition is used in a direct current mode. This is one of the reasons why regular break times are necessary during deposition, to restore the initial electrolyte concentrations everywhere in the solution.

Accumulation of Dihydrogen Bubbles
The main electrochemical reaction involved in the process is the reduction of water according to reaction (2). This reaction produces dihydrogen bubbles on the surface of the cathode, where the deposition of the coating is expected. Most of the dihydrogen bubbles escape quickly from the cathode, but some of them remain adsorbed on the surface. These bubbles prevent uniform deposition and promote the formation of many porosities that reduce the mechanical properties of the calcium phosphate coating. The cohesion of the layer and its adhesion to the substrate are particularly impacted. The SEM image of Figure 9 shows an example of the porosities caused by adsorbed dihydrogen bubbles on a calcium phosphate coating electrodeposited in direct current mode.
Coatings 2022, 12, x FOR PEER REVIEW 8 of 25 molar ratio is generally chosen with the perspective to produce hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), the gold standard among calcium phosphates, whose calcium to phosphorus atomic ratio is 1.67. However, despite this molar ratio in solution, very few articles show electrodeposited calcium phosphate coatings with the stoichiometry of hydroxyapatite. This could be the result of the mobility of the ions in the solution that modifies the local concentrations of calcium and phosphate ions in the vicinity of the electrodes. During the electrochemical process, the ions move under the influence of the electric field between the two electrodes. The cations move toward the cathode, and the anions move toward the anode [116,117]. The longer the deposition, the more local concentrations in the solution are modified and impact the stoichiometry of the electrodeposited coating. This implies a limitation of the process duration when electrodeposition is used in a direct current mode. This is one of the reasons why regular break times are necessary during deposition, to restore the initial electrolyte concentrations everywhere in the solution.

Accumulation of Dihydrogen Bubbles
The main electrochemical reaction involved in the process is the reduction of water according to reaction (2). This reaction produces dihydrogen bubbles on the surface of the cathode, where the deposition of the coating is expected. Most of the dihydrogen bubbles escape quickly from the cathode, but some of them remain adsorbed on the surface. These bubbles prevent uniform deposition and promote the formation of many porosities that reduce the mechanical properties of the calcium phosphate coating. The cohesion of the layer and its adhesion to the substrate are particularly impacted. The SEM image of Figure  9 shows an example of the porosities caused by adsorbed dihydrogen bubbles on a calcium phosphate coating electrodeposited in direct current mode. The higher the current density, the more dihydrogen bubbles are produced [118]. Therefore, the maximum current density value is limited by the number of bubbles produced by the process. This implies a limitation of the pH values reachable in the vicinity of the cathode, i.e., a limitation of the chemical compositions the process can produce. Since dihydrogen bubbles impose some limitations on the stoichiometry of the synthesized calcium phosphate coatings, the surface bioactivity of the implant is affected. This is one of the reasons why regular break times are necessary during deposition to reduce the accumulation of disturbing dihydrogen bubbles on the surface of the cathode.

Advantages of Pulsed Current Electrodeposition
The use of pulsed current is an efficient solution to solve the problems described above. The idea is to provide some regular break times (toff) during deposition (ton) to restore the initial experimental conditions (Figure 10). The higher the current density, the more dihydrogen bubbles are produced [118]. Therefore, the maximum current density value is limited by the number of bubbles produced by the process. This implies a limitation of the pH values reachable in the vicinity of the cathode, i.e., a limitation of the chemical compositions the process can produce. Since dihydrogen bubbles impose some limitations on the stoichiometry of the synthesized calcium phosphate coatings, the surface bioactivity of the implant is affected. This is one of the reasons why regular break times are necessary during deposition to reduce the accumulation of disturbing dihydrogen bubbles on the surface of the cathode.

Advantages of Pulsed Current Electrodeposition
The use of pulsed current is an efficient solution to solve the problems described above. The idea is to provide some regular break times (t off ) during deposition (t on ) to restore the initial experimental conditions (Figure 10). Different experimental protocols for pulsed currents are described in the literature, with short or long break times. Most protocols describe deposition times and break times of the same duration, but longer break times are also possible. Various durations can be used, ranging from a few microseconds to tens of seconds [72][73][74][75][119][120][121]. However, in all these works, the authors note several advantages of using pulsed currents, describing the improved properties of the electrodeposited calcium phosphate coatings. The authors describe more uniform calcium phosphate coatings with less porosity (Figure 11).

Higher Current Densities
As previously described, the current density values are limited because of their impact on the local ionic concentrations in the solution and on the number of dihydrogen bubbles produced. Both phenomena are undesirable and must be reduced to ensure appropriate electrodeposition of calcium phosphate coatings.
When electrodeposition is carried out in direct current mode, current densities are limited to a maximum of 10 mA cm −2 [122]. Beyond this value, the generated dihydrogen bubbles damage the electrodeposited coating [118]. This maximum current density can be used to produce a calcium-deficient apatite according to reaction (16). Typically, this phase has a calcium to phosphorus atomic ratio between 1.5 and 1.6. After post-deposition thermal annealing at a temperature higher than 800 °C, calcium-deficient apatite crystallizes into a biphasic compound made of hydroxyapatite and β-tricalcium phosphate according to reaction (18) [109]. The proportion of each crystallized phase depends on the stoichiometry of the calcium-deficient apatite, which is described by its calcium to phosphorus atomic ratio.
When electrodeposition is used in a pulsed current mode, the regular break times during the process are efficient for homogenizing the electrolyte solution and letting the Surface homogène Different experimental protocols for pulsed currents are described in the literature, with short or long break times. Most protocols describe deposition times and break times of the same duration, but longer break times are also possible. Various durations can be used, ranging from a few microseconds to tens of seconds [72][73][74][75][119][120][121]. However, in all these works, the authors note several advantages of using pulsed currents, describing the improved properties of the electrodeposited calcium phosphate coatings. The authors describe more uniform calcium phosphate coatings with less porosity (Figure 11). Different experimental protocols for pulsed currents are described in the literature, with short or long break times. Most protocols describe deposition times and break times of the same duration, but longer break times are also possible. Various durations can be used, ranging from a few microseconds to tens of seconds [72][73][74][75][119][120][121]. However, in all these works, the authors note several advantages of using pulsed currents, describing the improved properties of the electrodeposited calcium phosphate coatings. The authors describe more uniform calcium phosphate coatings with less porosity (Figure 11).

Higher Current Densities
As previously described, the current density values are limited because of their impact on the local ionic concentrations in the solution and on the number of dihydrogen bubbles produced. Both phenomena are undesirable and must be reduced to ensure appropriate electrodeposition of calcium phosphate coatings.
When electrodeposition is carried out in direct current mode, current densities are limited to a maximum of 10 mA cm −2 [122]. Beyond this value, the generated dihydrogen bubbles damage the electrodeposited coating [118]. This maximum current density can be used to produce a calcium-deficient apatite according to reaction (16). Typically, this phase has a calcium to phosphorus atomic ratio between 1.5 and 1.6. After post-deposition thermal annealing at a temperature higher than 800 °C, calcium-deficient apatite crystallizes into a biphasic compound made of hydroxyapatite and β-tricalcium phosphate according to reaction (18) [109]. The proportion of each crystallized phase depends on the stoichiometry of the calcium-deficient apatite, which is described by its calcium to phosphorus atomic ratio.
When electrodeposition is used in a pulsed current mode, the regular break times during the process are efficient for homogenizing the electrolyte solution and letting the Surface homogène

Higher Current Densities
As previously described, the current density values are limited because of their impact on the local ionic concentrations in the solution and on the number of dihydrogen bubbles produced. Both phenomena are undesirable and must be reduced to ensure appropriate electrodeposition of calcium phosphate coatings.
When electrodeposition is carried out in direct current mode, current densities are limited to a maximum of 10 mA cm −2 [122]. Beyond this value, the generated dihydrogen bubbles damage the electrodeposited coating [118]. This maximum current density can be used to produce a calcium-deficient apatite according to reaction (16). Typically, this phase has a calcium to phosphorus atomic ratio between 1.5 and 1.6. After post-deposition thermal annealing at a temperature higher than 800 • C, calcium-deficient apatite crystallizes into a biphasic compound made of hydroxyapatite and β-tricalcium phosphate according to reaction (18) [109]. The proportion of each crystallized phase depends on the stoichiometry of the calcium-deficient apatite, which is described by its calcium to phosphorus atomic ratio.
When electrodeposition is used in a pulsed current mode, the regular break times during the process are efficient for homogenizing the electrolyte solution and letting the dihydrogen bubbles escape from the cathode surface. Therefore, the impact of the two unfavorable phenomena is reduced. The range of usable current densities increases, giving access to an extended range of chemical compositions. Current densities of up to 15 mA cm −2 can be used to reach higher pH values and reduce the calcium deficiency of the apatite coating. Another solution to further increase the pH value in the vicinity of the cathode consists of adding hydrogen peroxide (H 2 O 2 ) to the electrolyte solution. Hydrogen peroxide is a strong oxidative reagent whose reduction at the cathode produces hydroxide ions according to the reaction (20): However, the amount of hydrogen peroxide in the electrolytic solution is limited to avoid the overproduction of hydroxide ions that prevent an appropriate deposition of the coating [123]. When combining an optimized pulsed current with a 9 vol.% H 2 O 2 concentration, a stoichiometric hydroxyapatite coating with a calcium to phosphorus atomic ratio of 1.67 is produced according to reaction (17). The obtained coating is less porous and composed of thin needles agglomerates that form spheroids of 1 µm in diameter. This means that the process can be used to produce all the calcium phosphate phases shown in Table 1 or a mixture of these phases. The low current densities of about 1 mA cm −2 produce brushite [122]. Intermediate current densities with values ranging from 2 mA cm −2 to 15 mA cm −2 produce octacalcium phosphate and calcium-deficient apatite [111]. Therefore, the combination of a current density of 15 mA cm −2 and hydrogen peroxide produces stoichiometric hydroxyapatite [72,73,85]. The bioactivity of the calcium phosphate coating can be chosen from a more soluble and reactive compound (brushite) to a more stable material (hydroxyapatite). This flexibility in composition gives full control over the kinetics of interactions between the bone-implant and the body environment, i.e., full control over the bioactivity of the biomaterial.

Improved Morphology and Roughness
The electrodeposited calcium phosphate coatings are made of crystallites that grow during deposition. The direct current mode produces crystallites that have the morphology of needles of about 1 µm in size stacked one upon another ( Figure 12). Sharp microneedles are harmful to bone cells, preventing attachment and spreading [124,125].
Coatings 2022, 12, x FOR PEER REVIEW 10 of 25 dihydrogen bubbles escape from the cathode surface. Therefore, the impact of the two unfavorable phenomena is reduced. The range of usable current densities increases, giving access to an extended range of chemical compositions. Current densities of up to 15 mA cm −2 can be used to reach higher pH values and reduce the calcium deficiency of the apatite coating. Another solution to further increase the pH value in the vicinity of the cathode consists of adding hydrogen peroxide (H2O2) to the electrolyte solution. Hydrogen peroxide is a strong oxidative reagent whose reduction at the cathode produces hydroxide ions according to the reaction (20): However, the amount of hydrogen peroxide in the electrolytic solution is limited to avoid the overproduction of hydroxide ions that prevent an appropriate deposition of the coating [123]. When combining an optimized pulsed current with a 9 vol.% H2O2 concentration, a stoichiometric hydroxyapatite coating with a calcium to phosphorus atomic ratio of 1.67 is produced according to reaction (17). The obtained coating is less porous and composed of thin needles agglomerates that form spheroids of 1 μm in diameter. This means that the process can be used to produce all the calcium phosphate phases shown in Table 1 or a mixture of these phases. The low current densities of about 1 mA cm −2 produce brushite [122]. Intermediate current densities with values ranging from 2 mA cm −2 to 15 mA cm −2 produce octacalcium phosphate and calcium-deficient apatite [111]. Therefore, the combination of a current density of 15 mA cm −2 and hydrogen peroxide produces stoichiometric hydroxyapatite [72,73,85]. The bioactivity of the calcium phosphate coating can be chosen from a more soluble and reactive compound (brushite) to a more stable material (hydroxyapatite). This flexibility in composition gives full control over the kinetics of interactions between the bone-implant and the body environment, i.e., full control over the bioactivity of the biomaterial.

Improved Morphology and Roughness
The electrodeposited calcium phosphate coatings are made of crystallites that grow during deposition. The direct current mode produces crystallites that have the morphology of needles of about 1 μm in size stacked one upon another ( Figure 12). Sharp microneedles are harmful to bone cells, preventing attachment and spreading [124,125]. On the other hand, pulsed current electrodeposition produces smaller crystallites that agglomerate to form spheroids (Figure 13). On the other hand, pulsed current electrodeposition produces smaller crystallites that agglomerate to form spheroids ( Figure 13). This characteristic morphology is more beneficial to bone cells and induces a decrease in the roughness of the coating. Morphology and roughness are two key parameters of calcium phosphate coatings, which are known to affect cell adhesion, spreading, proliferation, and differentiation. However, osteoblastic cell adhesion is a complex phenomenon and not only a simple physical attachment of cells [126,127]. Surface roughness is necessary, but only in a specific range. Roughness values greater than 2 µ m inhibit osteoblastic cell adhesion because the long distances between the peaks and valleys are unfavorable to the formation of osteoblastic pseudopodia [128,129]. Cairns et al. explain that regular smooth topography significantly increases osteocalcin expression and alkaline phosphatase activity, which promote bone cell growth [130]. Valleys are necessary to promote cell localization and stretch, and peaks of appropriate size are suitable to facilitate cell adhesion. Pulsed electrodeposition produces calcium phosphate coatings with roughness values of ca. 1 μm and below, which is in the range of the most appropriate values for the best cell behavior [131,132].

Enhanced Mechanical Properties
Because of the break times during electrodeposition in pulsed current mode, the dihydrogen bubbles produced by the reduction of water can easily escape from the cathode surface. The nucleation and growth of the calcium phosphate coatings are less disturbed by the bubbles, resulting in the densification of the electrodeposited coatings. Scratch test and nanoindentation measurements show that pulsed electrodeposition improves adhesion, apparent Young's modulus, and hardness of calcium phosphate coatings compared to those obtained in direct current mode [133].
Post-deposition thermal annealing can be used to densify the coating [134][135][136]. Temperatures up to 550 °C are generally used for air treatments to avoid oxidation of the metallic substrate. Under a controlled atmosphere (e.g., argon or vacuum), temperatures up to 1000 °C have been described [111]. The corresponding improvement in adhesion is generally studied by a standardized measurement of tensile adhesion according to the international standard ISO 13779-4 ( Figure 14) [137]. This characteristic morphology is more beneficial to bone cells and induces a decrease in the roughness of the coating. Morphology and roughness are two key parameters of calcium phosphate coatings, which are known to affect cell adhesion, spreading, proliferation, and differentiation. However, osteoblastic cell adhesion is a complex phenomenon and not only a simple physical attachment of cells [126,127]. Surface roughness is necessary, but only in a specific range. Roughness values greater than 2 µm inhibit osteoblastic cell adhesion because the long distances between the peaks and valleys are unfavorable to the formation of osteoblastic pseudopodia [128,129]. Cairns et al. explain that regular smooth topography significantly increases osteocalcin expression and alkaline phosphatase activity, which promote bone cell growth [130]. Valleys are necessary to promote cell localization and stretch, and peaks of appropriate size are suitable to facilitate cell adhesion. Pulsed electrodeposition produces calcium phosphate coatings with roughness values of ca. 1 µm and below, which is in the range of the most appropriate values for the best cell behavior [131,132].

Enhanced Mechanical Properties
Because of the break times during electrodeposition in pulsed current mode, the dihydrogen bubbles produced by the reduction of water can easily escape from the cathode surface. The nucleation and growth of the calcium phosphate coatings are less disturbed by the bubbles, resulting in the densification of the electrodeposited coatings. Scratch test and nanoindentation measurements show that pulsed electrodeposition improves adhesion, apparent Young's modulus, and hardness of calcium phosphate coatings compared to those obtained in direct current mode [133].
Post-deposition thermal annealing can be used to densify the coating [134][135][136]. Temperatures up to 550 • C are generally used for air treatments to avoid oxidation of the metallic substrate. Under a controlled atmosphere (e.g., argon or vacuum), temperatures up to 1000 • C have been described [111]. The corresponding improvement in adhesion is generally studied by a standardized measurement of tensile adhesion according to the international standard ISO 13779-4 ( Figure 14 Briefly, a Ti6Al4V cylinder (25 mm in diameter and 25 mm in height) is coated with calcium phosphate and the coated surface is pasted against another Ti6Al4V cylinder coated with adhesive glue (Figure 14a). After polymerization of the glue, the system is exposed to an increasing load applied by a standard tensile machine (Figure 14b) until a total removal of the coating (Figure 14c). The test is repeated five times to obtain an average adhesion value. The resulting adhesion values must be greater than 15 MPa to be accepted by the bone-implant industry [138].

Ionic Substitution to Enhance the Properties of Electrodeposited Coatings
A powerful property of electrodeposition is the possibility of adding ionic substituents to the electrolyte solution used for the synthesis. During deposition, the ionic substituents are integrated into the calcium phosphate lattice to enhance the biological properties of the coating. Several ions are described in the scientific literature with different biological effects [139][140][141][142][143][144][145][146][147].

Divalent Cations
The most common substitutions of electrodeposited calcium phosphate coatings are obtained from divalent cations (M 2+ ) substituting calcium (Ca 2+ ) according to reaction (21): Among the divalent cations capable of enhancing the biological properties of electrodeposited calcium phosphate coatings, Co 2+ , Cu 2+ , Mg 2+ , Mn 2+ , Sr 2+ , Zn 2+ are particularly studied in the scientific literature.

Cobalt (Co 2+ )
The addition of cobalt to the calcium phosphate coating aims to promote angiogenesis in vivo, i.e., the neovascularization of newly formed bone tissues. These new blood vessels are involved in the supply of nutrients to bone cells and the transport of macromolecules during bone repair and regeneration [148]. For the efficient promotion of angiogenesis and to prevent any toxic effect of cobalt ions within the body, a 5 at.% substitution is commonly recommended [149].

Copper (Cu 2+ )
Copper is well known to provide antibacterial properties to various surfaces, particularly against Escherichia coli (E. coli) strains [150]. Copper reduces the permeability of the Briefly, a Ti6Al4V cylinder (25 mm in diameter and 25 mm in height) is coated with calcium phosphate and the coated surface is pasted against another Ti6Al4V cylinder coated with adhesive glue (Figure 14a). After polymerization of the glue, the system is exposed to an increasing load applied by a standard tensile machine (Figure 14b) until a total removal of the coating (Figure 14c). The test is repeated five times to obtain an average adhesion value. The resulting adhesion values must be greater than 15 MPa to be accepted by the bone-implant industry [138].

Ionic Substitution to Enhance the Properties of Electrodeposited Coatings
A powerful property of electrodeposition is the possibility of adding ionic substituents to the electrolyte solution used for the synthesis. During deposition, the ionic substituents are integrated into the calcium phosphate lattice to enhance the biological properties of the coating. Several ions are described in the scientific literature with different biological effects [139][140][141][142][143][144][145][146][147].

Divalent Cations
The most common substitutions of electrodeposited calcium phosphate coatings are obtained from divalent cations (M 2+ ) substituting calcium (Ca 2+ ) according to reaction (21): Among the divalent cations capable of enhancing the biological properties of electrodeposited calcium phosphate coatings, Co 2+ , Cu 2+ , Mg 2+ , Mn 2+ , Sr 2+ , Zn 2+ are particularly studied in the scientific literature.

Cobalt (Co 2+ )
The addition of cobalt to the calcium phosphate coating aims to promote angiogenesis in vivo, i.e., the neovascularization of newly formed bone tissues. These new blood vessels are involved in the supply of nutrients to bone cells and the transport of macromolecules during bone repair and regeneration [148]. For the efficient promotion of angiogenesis and to prevent any toxic effect of cobalt ions within the body, a 5 at.% substitution is commonly recommended [149].

Copper (Cu 2+ )
Copper is well known to provide antibacterial properties to various surfaces, particularly against Escherichia coli (E. coli) strains [150]. Copper reduces the permeability of the cell membrane of bacteria, preventing their replication, and finally causing their death [151]. However, the amount of copper in the physiological environment must be limited to prevent any toxic effect on bone cells at high concentrations [152].

Magnesium (Mg 2+ )
Magnesium is known to promote bone densification. An appropriate amount of magnesium in the implant coating improves osteoblastic cell attachment and proliferation. Magnesium also increases the production of alkaline phosphatase, the main enzyme involved in the mineralization of the extracellular matrix of bone [153][154][155][156].

Manganese (Mn 2+ )
Manganese is mainly described for its ability to regulate osteoblast differentiation, control bone resorption, and promote cell adhesion [157]. Furthermore, manganese ions promote the production of osteocalcin, a protein produced by osteoblasts and involved in the bone formation process [158].

Strontium (Sr 2+ )
The use of strontium is well known in the form of strontium ranelate, a widely used drug for the treatment of bone defects such as postmenopausal osteoporosis. Strontium stimulates bone formation and inhibits bone resorption, which explains the increase in bone density in patients [159,160]. A 5 at.% substitution shows the best results in osteoblast cell activity and differentiation, and in osteoclast cell proliferation [161][162][163].

Zinc (Zn 2+ )
Zinc in calcium phosphate coatings is described for several biological actions. Zinc mainly provides antibacterial and anti-inflammatory properties, but the promotion of bone formation and regeneration is also described in the literature [164]. Bone cell adhesion and viability are generally improved due to the presence of a few percent of zinc in the calcium phosphate coatings [165,166].

Monovalent Cations
Several monovalent cations are also described for their interesting biological action.

Silver (Ag + )
Silver is well-known to provide remarkable antibacterial properties to various surfaces. The bacterial inhibition is due to the ability of silver to penetrate the cytoplasm of bacteria. Silver can interact with thiol groups in proteins, inhibiting cellular respiration and causing the death of bacteria [173]. Another mechanism is attributed to the ability of silver to bind to microbial DNA to prevent bacterial replication [174,175].

Sodium (Na + )
Substitution with sodium ions enhances the biomineralization capacity of calcium phosphates in the physiological environment. Moreover, the positive contribution of sodium to bone cell adhesion and proliferation has been observed in vivo [176,177].

Anions
Anionic substitutions are described in the scientific literature in the case of hydroxyapatite. Anions can substitute phosphate groups to produce Ca 10 (PO 4 ) 6−x M x (OH) 2 compounds or hydroxyl groups to produce Ca 10 (PO 4 ) 6 M x (OH) 2−x [146]. The most common anions used to substitute electrodeposited calcium phosphate coatings are CO 2− 3 , Cl − , F − , and SiO 4− 4 .
5.3.1. Carbonate (CO 2− 3 ) Carbonate ions are naturally present in electrolyte solutions at room temperature because atmospheric carbon dioxide (CO 2 ) dissolves in water to produce carbonic acid (H 2 CO 3 ) according to reaction (22).
Carbonic acid is a weak dibasic acid characterized by two dissociation constants, pKa 1 = 6.8 and pKa 2 = 9.9. When the pH of the electrolyte solution increases, bicarbonate ions (HCO − 3 ) and carbonate ions (CO 2− 3 ) are formed [85]: The chemical composition of carbonate calcium phosphates is very similar to that of bone apatite. Substitution with carbonate ions induces higher solubility and bioactivity of the calcium phosphate coating in the physiological environment [80,178,179].

Fluorine (F − )
The use of fluorine is widespread in tooth care products to provide antibacterial properties. Substituting calcium phosphates with fluorine also stimulates the formation of the extracellular matrix and significantly improves bone cell proliferation and alkaline phosphatase activity [180,181].

Silicates (SiO 4− 4 )
Calcium phosphate substituted with silicates improves osteoblast attachment, proliferation, and differentiation. Silicates also favor the formation of extracellular matrix and increase alkaline phosphatase activity and osteocalcin expression [182,183].

Next Generation of Substituted Calcium Phosphate Coatings
Due to the variety of biological behaviors previously described, the multi-substitution of calcium phosphate coatings is an attractive solution to combine several biological properties of different ions [184][185][186][187][188][189][190][191][192][193]. For example, Bracci et al. describe multi-substitution with three divalent cations (Mg 2+ , Sr 2+ , and Mn 2+ ) to cumulate their positive impact on bone cell activity [194]. Another development proposed by Furko et al. is the electrodeposition of calcium phosphate coatings substituted with Ag + and Zn 2+ to provide simultaneous antibacterial and anti-inflammatory properties to the surface of the bone-implant [195]. They also experiment with multi-elemental substitution of electrodeposited calcium phosphate coatings [196,197]. Other works describe electrodeposited calcium phosphate coatings that are simultaneously substituted by anions and cations. Olivier et al. use CO 2− 3 and Sr 2+ to produce coatings with a biomimetic chemical composition capable of improving bone cell proliferation [80]. Huang et al. substitute calcium phosphate coatings with F − and Sr 2+ to provide antibacterial properties and improve bone formation [198]. Bir et al. combine the antibacterial effects provided by F − and Ag + to inhibit more bacterial growth on the surface of the bone-implant [199]. Many other combinations remain to be explored with different amounts of cations and anions added to the calcium phosphate crystal lattice. Ideally, the resulting coating will combine all the biological enhancements previously described ( Table 2).  [183] Another possible development is the substitution with new ions, already described in the literature to substitute calcium phosphate materials, but never in the case of electrodeposited coatings. For example, iron (Fe 2+ or Fe 3+ ) is known to improve osteogenesis, simultaneously providing anticancer and antibacterial properties to calcium phosphates [200][201][202]. Chloride ions (Cl − ) are known to promote cell proliferation and osteoconductivity because of their ability to develop an acidic environment on the surface of bones. This acidity supports the action of osteoclasts in the bone resorption process [203][204][205]. Lithium (Li + ) improves bone regeneration by promoting alkaline phosphatase and osteogenic gene expression in osteoblasts [206,207]. Cerium (Ce 3+ or Ce 4+ ) is used for effective antibacterial properties against E. coli and S. aureus [208,209]. Bismuth (Bi 3+ ), gallium (Ga 3+ ), and selenium (SeO 2− 3 ) show simultaneous positive impacts against bacteria and tumor cells [210][211][212][213][214][215][216]. Erbium (Er 3+ ), europium (Eu 3+ ), or terbium (Tb 3+ ) are added for their photoluminescence properties used in biological imaging systems [217][218][219][220][221][222]. The variety of all these ions and their biological impacts on calcium phosphate coatings used for bone implant applications will be part of the upcoming developments of the electrodeposition process.

Conclusions
In this review, the three steps to synthesize calcium phosphate coatings by electrodeposition were described: electrochemical reactions, acid-base reactions, and precipitation reactions. The process has limitations in the direct current mode because of the production of undesired dihydrogen bubbles due to the reduction of water, the solvent of the electrolyte solution. To solve this problem, pulsed current electrodeposition is a relevant solution that produces uniform calcium phosphate coatings with improved morphology, roughness, and mechanical properties. Moreover, the addition of hydrogen peroxide to the electrolytic solution provides more control over the chemical composition of the coating. Finally, the ionic substitution of electrodeposited calcium phosphate coatings was reviewed, and some new perspectives on the process were described. Multi-substitution or substitution with new ions will be the next development to improve the process.