**2. HAp coating**

HAp (Ca10(PO4)6(OH)2), which is the main inorganic component in the mammal bone or tooth [1], has attracted attention as a surface‐coating compound because of its high osteoconductiv‐ ity. Many pyro methods of forming HAp and other calcium phosphate coatings on metallic substrates have been reported (e.g., plasma spraying [2, 3], sol‐gel method [4,5], electron beam sputtering method [6], and ion beam sputtering method [7]). However, all have weak points in relation to coating with HAp on complex‐shaped implants. Plasma spraying remains the most commonly used technique for HAp coating on a Ti or Ti alloy substrate in the fabrication of artificial joint replacements [1] and in endosseous dental implants [2]. On the other hand, many hydro coating techniques (e.g., cathodic electrolysis method [8‐10], electrophoretic method [11, 12], and thermal substrate method [13‐18]) have been proposed as approaches to forming thin film coatings on metallic substrates. The cathodic electrolysis and thermal substrate methods are single‐step coating techniques in an aqueous solution, and they coat the HAp directly from the solution. The electrophoretic method is omitted from this review because it uses HAp formed by other methods in advance, despite the hydroprocessing. Therefore, in this paper, we describe the cathodic electrolysis and thermal substrate methods.

#### **2.1. Theory of HAp coating using hydroprocessing**

It is known that the solubility of HAp in an aqueous solution decreases with increasing temperature and that the relationship between the HAp solubility product, *K*SP/(mol dm–3) 9 , and the temperature, *T*/K, is given by [19]:

$$
\log K\_{Sp} = -8219.41 \, / \, T - 1.6657 \, - \, 0.098215T. \tag{1}
$$

Therefore, heating an aqueous solution containing Ca2+ and PO4 3– ions results in the precipi‐ tation of calcium phosphates, such as HAp, in the solution.

The ionic product of HAp, *K*IP/(mol L–1) 9 , is expressed as follows:

$$K\_{IP} = \left[\text{Ca}^{2+}\right]^5 \left[\text{PO}\_4^{3-}\right]^3 \left[\text{OH}^-\right]\_{\prime} \tag{2}$$

where [X] indicates the molar concentration (mol L–1) of ionic species X. The increase in [Ca2+] or [PO4 3–] content or pH value in the solution initiates the precipitation of HAp because *K*IP achieves *K*SP. Moreover, [PO4 3–] increases with increasing pH value (Figure 1). Therefore, the increase in pH directly accelerates the precipitation of HAp, which indirectly increases the [PO4 3–] content.

Figure 2 shows the solubility curves of various compounds on a calcium orthophosphate [19]; as shown, there are many compounds other than HAp. This figure indicates that CaHPO4 (DCPA) is the most stable compound at pH < 5, with HAp the most stable at pH > 5. Therefore, HAp can be easily obtained in a solution where pH > 5 and where the ion content and temperature are controlled. However, HAp cannot precipitate in the pH < 5 solution, and hydroprocessing using the precipitation phenomenon in the aqueous solution cannot give β‐ Ca3(PO4)2 (β‐TCP), a bioactive compound.

**Figure 1.** Logarithmic concentration diagram for orthophosphoric acid.

**2. HAp coating**

Biomedical Engineering

288

**2.1. Theory of HAp coating using hydroprocessing**

Therefore, heating an aqueous solution containing Ca2+ and PO4

9

5 3 2+ 3– – *KIP* Ca PO OH , <sup>4</sup>

where [X] indicates the molar concentration (mol L–1) of ionic species X. The increase in [Ca2+]

increase in pH directly accelerates the precipitation of HAp, which indirectly increases the

Figure 2 shows the solubility curves of various compounds on a calcium orthophosphate [19]; as shown, there are many compounds other than HAp. This figure indicates that CaHPO4 (DCPA) is the most stable compound at pH < 5, with HAp the most stable at pH > 5. Therefore,

3–] content or pH value in the solution initiates the precipitation of HAp because *K*IP

tation of calcium phosphates, such as HAp, in the solution.

and the temperature, *T*/K, is given by [19]:

The ionic product of HAp, *K*IP/(mol L–1)

achieves *K*SP. Moreover, [PO4

3–] content.

or [PO4

[PO4

HAp (Ca10(PO4)6(OH)2), which is the main inorganic component in the mammal bone or tooth [1], has attracted attention as a surface‐coating compound because of its high osteoconductiv‐ ity. Many pyro methods of forming HAp and other calcium phosphate coatings on metallic substrates have been reported (e.g., plasma spraying [2, 3], sol‐gel method [4,5], electron beam sputtering method [6], and ion beam sputtering method [7]). However, all have weak points in relation to coating with HAp on complex‐shaped implants. Plasma spraying remains the most commonly used technique for HAp coating on a Ti or Ti alloy substrate in the fabrication of artificial joint replacements [1] and in endosseous dental implants [2]. On the other hand, many hydro coating techniques (e.g., cathodic electrolysis method [8‐10], electrophoretic method [11, 12], and thermal substrate method [13‐18]) have been proposed as approaches to forming thin film coatings on metallic substrates. The cathodic electrolysis and thermal substrate methods are single‐step coating techniques in an aqueous solution, and they coat the HAp directly from the solution. The electrophoretic method is omitted from this review because it uses HAp formed by other methods in advance, despite the hydroprocessing. Therefore, in this paper, we describe the cathodic electrolysis and thermal substrate methods.

Micro-Nano Mechatronics — New Trends in Material, Measurement, Control, Manufacturing and Their Applications in

It is known that the solubility of HAp in an aqueous solution decreases with increasing temperature and that the relationship between the HAp solubility product, *K*SP/(mol dm–3)

log – 8219.41 / – 1.6657 – 0.098215 . *KT T SP* (1)

(2)

3–] increases with increasing pH value (Figure 1). Therefore, the

, is expressed as follows:

9 ,

3– ions results in the precipi‐

**Figure 2.** Solubility curves of calcium orthophosphoric compounds at 37 oC, depending on pH in aqueous solution. HAp: hydroxyapatite (Ca10(PO4)6(OH)2), TCP: calcium phosphate (Ca3(PO4)2), OCP: octacalcium phosphate (Ca8H2(PO4)6 5H2O), DCPA: dicalcium phospate anhydrous (CaHPO4), DCPD: dicalcium phospate dihydrate (CaHPO4 2H2O).

#### **2.2. Thermal substrate method in aqueous solution [13]**

This process involves passing an alternating current through a metallic sample immersed in an aqueous solution. The immersed metallic sample heats up to more than 100 ºC by Joule heating, even though the hydroprocessing occurs at atmospheric pressure (Figure 3). There‐ fore, this method can produce the special reaction conditions (>100 ºC in an aqueous solution) by not using the pressure vessel.

composed of HAp (Figure 4 (b)–(d)). From the EDX analysis, the molar ratio of calcium to phosphorous (Ca/P) of HAp was 1.41‐1.43. This shows the coated HAp was calcium deficient. The pH dependence of the solubility of the calcium phosphate compounds explains why the precipitate changed with increasing pH of the solution, i.e., the solubility curves of DCPA and HAp cross at approximately pH = 5 for various compounds of calcium phosphate [19]. The surface morphology of the precipitated HAp strongly depends on coating temperature: low temperature (40 ºC) gave net‐like HAp (Figure 4 (b)); high temperature (140 ºC) gave needle‐ like HAp (Figure 4 (d)); and mid temperature (60 ºC) gave plate‐like HAp (Figure 4 (c)). That is, by using hydroprocessing, we can control the crystalline form, which could not have been achieved using traditional methods. Figure 5 shows the scanning electron microscopy (SEM) photographs of the HAp‐coated samples on porous Ti alloy surfaces formed by sintering Ti6Al4V particles (ca. 100 μm in diameter) on cpTi substrates [16]. Heating at 100 ºC for 15 min. in a pH = 7 solution ledto HAp precipitation overthe entire surface oftheTi6Al4V sintered particles (on both front and back faces) and on the base cpTi substrate of the experimental samples. In particular, it was found that HAp precipitate was also detected at the sinter neck regions of adjacent particles and on the base substrate, while the original open‐pored geometry was maintained. Therefore, this method can be used to apply the HAp coating to a substrate

Hydroxyapatite Coating on Titanium Implants Using Hydroprocessing and Evaluation of their Osteoconductivity 291

**Figure 4.** SEM photographs of the surface of the samples treated by various methods.

with complex topography.

**Figure 3.** Experimental apparatus for HAp coating.

When the thermal substrate method in an aqueous solution is used, the fact that the solubility of HAp decreases with increasing temperature means that HAp precipitation occurs only on the substrate. It is important to coat HAp while controlling the concentration of the solute and the pH value ofthe solution and temperature, because they affect the degree of supersaturation of HAp in the solution (Eqs (1) and (2)). Figure 4 (a)–(d) shows the change in the surface morphology of the samples coated with HAp under controlled pH and temperature, whose foctors determined the degree of the supersaturation with respect to HAp [14, 15, 17, 18]. The precipitate at pH = 4.0 (Figure 4 (a)) appeared to pile up like bricks and was identified as DCPA, which is a stable compound. On the other hand, in the solution at pH = 8.0, the precipitate was

**Figure 4.** SEM photographs of the surface of the samples treated by various methods.

**2.2. Thermal substrate method in aqueous solution [13]**

by not using the pressure vessel.

Biomedical Engineering

290

**Figure 3.** Experimental apparatus for HAp coating.

This process involves passing an alternating current through a metallic sample immersed in an aqueous solution. The immersed metallic sample heats up to more than 100 ºC by Joule heating, even though the hydroprocessing occurs at atmospheric pressure (Figure 3). There‐ fore, this method can produce the special reaction conditions (>100 ºC in an aqueous solution)

Micro-Nano Mechatronics — New Trends in Material, Measurement, Control, Manufacturing and Their Applications in

Pyrex beaker Pyrex beaker

When the thermal substrate method in an aqueous solution is used, the fact that the solubility of HAp decreases with increasing temperature means that HAp precipitation occurs only on the substrate. It is important to coat HAp while controlling the concentration of the solute and the pH value ofthe solution and temperature, because they affect the degree of supersaturation of HAp in the solution (Eqs (1) and (2)). Figure 4 (a)–(d) shows the change in the surface morphology of the samples coated with HAp under controlled pH and temperature, whose foctors determined the degree of the supersaturation with respect to HAp [14, 15, 17, 18]. The precipitate at pH = 4.0 (Figure 4 (a)) appeared to pile up like bricks and was identified as DCPA, which is a stable compound. On the other hand, in the solution at pH = 8.0, the precipitate was

Cooling tube Cooling tube

Solution (0.2 dm3 Solution (0.2 dm )3)

Ti sample (in vivo) (2x5 mm) Ti sample (in vivo) (2x5 mm)

Ti sample (in vitro) (t0.3 mm) Ti sample (in vitro)(t0.3 mm)

Thermocouple Thermocouple

TC supporter TC supporter

Coolant Coolant

Copper lead rod (coated with epoxy resin) Copper lead rod (coated with epoxy resin)

Ammeter

Powerstat

~

Thermo-meter AC power supply AC power supply

composed of HAp (Figure 4 (b)–(d)). From the EDX analysis, the molar ratio of calcium to phosphorous (Ca/P) of HAp was 1.41‐1.43. This shows the coated HAp was calcium deficient. The pH dependence of the solubility of the calcium phosphate compounds explains why the precipitate changed with increasing pH of the solution, i.e., the solubility curves of DCPA and HAp cross at approximately pH = 5 for various compounds of calcium phosphate [19]. The surface morphology of the precipitated HAp strongly depends on coating temperature: low temperature (40 ºC) gave net‐like HAp (Figure 4 (b)); high temperature (140 ºC) gave needle‐ like HAp (Figure 4 (d)); and mid temperature (60 ºC) gave plate‐like HAp (Figure 4 (c)). That is, by using hydroprocessing, we can control the crystalline form, which could not have been achieved using traditional methods. Figure 5 shows the scanning electron microscopy (SEM) photographs of the HAp‐coated samples on porous Ti alloy surfaces formed by sintering Ti6Al4V particles (ca. 100 μm in diameter) on cpTi substrates [16]. Heating at 100 ºC for 15 min. in a pH = 7 solution ledto HAp precipitation overthe entire surface oftheTi6Al4V sintered particles (on both front and back faces) and on the base cpTi substrate of the experimental samples. In particular, it was found that HAp precipitate was also detected at the sinter neck regions of adjacent particles and on the base substrate, while the original open‐pored geometry was maintained. Therefore, this method can be used to apply the HAp coating to a substrate with complex topography.

Micro-Nano Mechatronics — New Trends in Material, Measurement, Control, Manufacturing and Their Applications in Biomedical Engineering 292

Natural bone contains CO3–Ap and a considerable amount of organic components, such as collagen (about 23 mass% [21]).Itis known thatthe hybridorganic–inorganic structure initiates pliable bone. Some researchers have reported the preparation of nanocomposites of HAp/ collagen and HAp/gelatin [28–30], as natural bone is considered a nanocomposite of mineral and proteins. Moreover, immobilization of collagen on implants displays a tighter fixation with the surrounding tissue, since the collagen behaves as an adhesive protein with cells because of the amino groups in the collagen molecules [31, 32]. From the viewpoint of osteoconductivity, we expected that preparing the HAp/collagen composite coating would be a more promising approach than using an individual coating of either CO3–Ap or HAp. In the solution to which acid‐soluble collagen is added, HAp/collagen or HAp/gelatin composite films are easily obtained on a substrate, depending on coating temperature. In general, as mammalian collagen rapidly denatures to gelatin at >45 ºC, HAp/collagen composite can be obtained at <40 ºC and HAp/gelatin composite at >50 ºC. Figure 4 (g)–(h) shows the surface of the samples coated in the pH = 8 solution with 72 mg L–1 collagen, derived from calf, at 140 ºC and 40 ºC (10–15 mass% collagen or gelatin in the film) [33]. The surface morphologies of HAp/ collagen and HAp/gelatin significantly depend on the coating temperature and are not affected by whether the composite film contains collagen or gelatin. That is, collagen and gelatin have only a small effect on the HAp crystal growth of the adsorption onto HAp. Hydroprocessing can be used to form HAp/collagen and HAp/gelatin composite films, which could not be formed using high‐temperature processing, and the content of collagen and gelatin in the films

Hydroxyapatite Coating on Titanium Implants Using Hydroprocessing and Evaluation of their Osteoconductivity 293

In the electrochemical technique, a redox reaction produces supersaturation of OH– ions near

thermal substrate method. This local effect induces heterogeneous nucleation on the metal substrate serving as the electrode. The addition of hydrogen peroxide to the solution prevents H2 gas generation at the cathodic electrode and promotes nucleation and growth of the HAp coating. Adding H2O2 to electrolytes enhances the formation of OH– ions at the solution– electrode interface at a lower cathodic potential, as described in the following reaction (3) [10]:

In this method, the surface morphology of the precipitated HAp greatly depends on coating temperature [34] in the same manner as in the thermal substrate method. The effect of temperature on the surface morphology of coated samples is shown in Figure 4 (i)–(j). The HAp crystals had a similar shape to those formed using the thermal substrate method, although the size of HAp crystals differed between the cathodic electrolysis and the thermal substrate methods. The molar ratio (Ca/P) of HAp was almost same as that using the thermal substrate method. The coatings at >100 ºC were conducted in the pressure vessel. When using

HAp/gelatin composite films are formed on a substrate, depending on coating temperature.

3– in the same manner as in the

– – HO+ 2 2 2e = 2OH . (3)

2– or collagen are added, CO3–Ap, HAp/collagen, or

can be controlled up to 60 mass%.

the electrolysis solution, to which CO3

**2.3. Cathodic electrolysis in aqueous solution [8‐10]**

the electrode in the aqueous solution containing Ca2+ and PO4

**Figure 5.** and/or cross-sectional views of the samples with surface roughness. (a)-(c) beads-sintered porous samples (as sintered), (d)(e) HAp coated on beads-sintered porous samples (thermal substrate method, 0.7 mM CaCl2+0.3 mM Ca(H2PO4)2, pH 7, 100 oC, 15 min.).

Biological apatite in natural bone does not appear in the form of pure HAp and it contains a considerable amount of carbonate ions [20] (about 7.4 mass% with respect to total bone and 11.4 mass% with respect to the inorganic component in natural bone [21]). Carbonate apatite (CO3–Ap), which replaces PO4 3– and/or OH– ions with CO3 2– ions, is similar to the inorganic component of bone, and it seems to be a more promising bioactive material than stoichiometric HAp, because CO3–Ap has greater solubility than pure HAp [20]. In addition, it has been reported that CaCO3 displays bioactivity, such as cell compatibility and hard tissue compati‐ bility [22, 23]; that is, CO3 2– is expected to influence biological reactivity and osteoconductive properties. It is also well known that the solubility of CaCO3 in an aqueous solution decreases with increasing temperature [24]. In the solution, when CO3 2– ions are added, CO3–Ap or CO3– Ap/CaCO3 composite films are easily obtained on a substrate. Typical SEM photographs of the surface of the samples are shown in Figure 4 (e)–(f), coated in the pH = 8 solution with <0.5 mM NaHCO3 added at 140 ºC for a period of 15 min., and afterthe steam autoclaving treatment (5 mass% CO3 in this film) [25, 26]. The precipitates coated from the solution with >0.5 mM NaHCO3 added contained CO3–Ap and CaCO3 at all temperatures, and the X‐ray diffraction spectra showed a mixture of calcite, vaterite, and aragonite. The crystalline form of CO3–Ap was changed, depending on the added NaHCO3 content, as well as coating temperature. In particular, adding a significant amount of NaHCO3 (>5 mM) brought about sphere‐like‐shaped CO3–Ap (Figure 4 (f)) in the 140 ºC coating. In CO3–Ap films, FT–IR analysis revealed that CO3 2– was substituted for PO4 3– (Type B CO3–Ap) in advance, which was similar to biological apatite [27], and adding more CO3 2– to the solution gave the substitution for OH– (Type A). Therefore, in the samples with <0.5 mM NaHCO3 added, Type B CO3–Ap was obtained, and in the samples with >5 mM NaHCO3 added (i.e., having the binary phase of CO3–Ap/CaCO3), Type AB CO3–Ap was formed.

Natural bone contains CO3–Ap and a considerable amount of organic components, such as collagen (about 23 mass% [21]).Itis known thatthe hybridorganic–inorganic structure initiates pliable bone. Some researchers have reported the preparation of nanocomposites of HAp/ collagen and HAp/gelatin [28–30], as natural bone is considered a nanocomposite of mineral and proteins. Moreover, immobilization of collagen on implants displays a tighter fixation with the surrounding tissue, since the collagen behaves as an adhesive protein with cells because of the amino groups in the collagen molecules [31, 32]. From the viewpoint of osteoconductivity, we expected that preparing the HAp/collagen composite coating would be a more promising approach than using an individual coating of either CO3–Ap or HAp. In the solution to which acid‐soluble collagen is added, HAp/collagen or HAp/gelatin composite films are easily obtained on a substrate, depending on coating temperature. In general, as mammalian collagen rapidly denatures to gelatin at >45 ºC, HAp/collagen composite can be obtained at <40 ºC and HAp/gelatin composite at >50 ºC. Figure 4 (g)–(h) shows the surface of the samples coated in the pH = 8 solution with 72 mg L–1 collagen, derived from calf, at 140 ºC and 40 ºC (10–15 mass% collagen or gelatin in the film) [33]. The surface morphologies of HAp/ collagen and HAp/gelatin significantly depend on the coating temperature and are not affected by whether the composite film contains collagen or gelatin. That is, collagen and gelatin have only a small effect on the HAp crystal growth of the adsorption onto HAp. Hydroprocessing can be used to form HAp/collagen and HAp/gelatin composite films, which could not be formed using high‐temperature processing, and the content of collagen and gelatin in the films can be controlled up to 60 mass%.

#### **2.3. Cathodic electrolysis in aqueous solution [8‐10]**

100 m

100 m

**Figure 5.** and/or cross-sectional views of the samples with surface roughness. (a)-(c) beads-sintered porous samples (as sintered), (d)(e) HAp coated on beads-sintered porous samples (thermal substrate method, 0.7 mM CaCl2+0.3 mM

Biological apatite in natural bone does not appear in the form of pure HAp and it contains a considerable amount of carbonate ions [20] (about 7.4 mass% with respect to total bone and 11.4 mass% with respect to the inorganic component in natural bone [21]). Carbonate apatite

3– and/or OH– ions with CO3

component of bone, and it seems to be a more promising bioactive material than stoichiometric HAp, because CO3–Ap has greater solubility than pure HAp [20]. In addition, it has been reported that CaCO3 displays bioactivity, such as cell compatibility and hard tissue compati‐

properties. It is also well known that the solubility of CaCO3 in an aqueous solution decreases

Ap/CaCO3 composite films are easily obtained on a substrate. Typical SEM photographs of the surface of the samples are shown in Figure 4 (e)–(f), coated in the pH = 8 solution with <0.5 mM NaHCO3 added at 140 ºC for a period of 15 min., and afterthe steam autoclaving treatment (5 mass% CO3 in this film) [25, 26]. The precipitates coated from the solution with >0.5 mM NaHCO3 added contained CO3–Ap and CaCO3 at all temperatures, and the X‐ray diffraction spectra showed a mixture of calcite, vaterite, and aragonite. The crystalline form of CO3–Ap was changed, depending on the added NaHCO3 content, as well as coating temperature. In particular, adding a significant amount of NaHCO3 (>5 mM) brought about sphere‐like‐shaped CO3–Ap (Figure 4 (f)) in the 140 ºC coating. In CO3–Ap films, FT–IR analysis revealed that

Therefore, in the samples with <0.5 mM NaHCO3 added, Type B CO3–Ap was obtained, and in the samples with >5 mM NaHCO3 added (i.e., having the binary phase of CO3–Ap/CaCO3),

**(c)**

**(e)**

2– is expected to influence biological reactivity and osteoconductive

3– (Type B CO3–Ap) in advance, which was similar to biological

2– to the solution gave the substitution for OH– (Type A).

50 m

50 m

2– ions, is similar to the inorganic

2– ions are added, CO3–Ap or CO3–

**(b)**

Micro-Nano Mechatronics — New Trends in Material, Measurement, Control, Manufacturing and Their Applications in

**(d)**

0.5mm

with increasing temperature [24]. In the solution, when CO3

**(a)**

Biomedical Engineering

292

Ca(H2PO4)2, pH 7, 100 oC, 15 min.).

(CO3–Ap), which replaces PO4

2– was substituted for PO4

apatite [27], and adding more CO3

Type AB CO3–Ap was formed.

bility [22, 23]; that is, CO3

CO3

In the electrochemical technique, a redox reaction produces supersaturation of OH– ions near the electrode in the aqueous solution containing Ca2+ and PO4 3– in the same manner as in the thermal substrate method. This local effect induces heterogeneous nucleation on the metal substrate serving as the electrode. The addition of hydrogen peroxide to the solution prevents H2 gas generation at the cathodic electrode and promotes nucleation and growth of the HAp coating. Adding H2O2 to electrolytes enhances the formation of OH– ions at the solution– electrode interface at a lower cathodic potential, as described in the following reaction (3) [10]:

$$\text{CH}\_2\text{O}\_2 + 2\text{e}^- = 2\text{OH}^-.\tag{3}$$

In this method, the surface morphology of the precipitated HAp greatly depends on coating temperature [34] in the same manner as in the thermal substrate method. The effect of temperature on the surface morphology of coated samples is shown in Figure 4 (i)–(j). The HAp crystals had a similar shape to those formed using the thermal substrate method, although the size of HAp crystals differed between the cathodic electrolysis and the thermal substrate methods. The molar ratio (Ca/P) of HAp was almost same as that using the thermal substrate method. The coatings at >100 ºC were conducted in the pressure vessel. When using the electrolysis solution, to which CO3 2– or collagen are added, CO3–Ap, HAp/collagen, or HAp/gelatin composite films are formed on a substrate, depending on coating temperature.

> Figure 6 shows the bone–implant contact ratios, *R*B–I, of the samples coated under the various conditions mentioned above and classified based on the following four surface morphologies: (A) needle‐like, (B) plate‐like, (C) net‐like, and (D) sphere‐like. The samples are then compared with the control implant ((E) noncoated Ti). In Fig. 6, the samples are distinguished according to color based on whether or not the coating contained CaCO3 and collagen or gelatin (white: HAp; gray: CO3–Ap or HAp/gelatin; black: CO3–Ap/CaCO3 or HAp/collagen). The *R*B–I value of HAp‐coated samples (white bar) is the same as or higher than that of the as‐polished one (E). In particular, *R*B–I in the cancellous bone part is highest in the sample coated with the needle‐like HAp (A‐1). The influence of the different surface morphologies on *R*B–I is apparent [17, 18]. A small amount of CO3 included in CO3–Ap does not influence osteoconductivity, and an increased amount of CO3 (>15 mass%CO3), including that in CO3–Ap/CaCO3, has a negative effect on (black bar in (A‐1), (B‐1), (C‐1), and (D‐1)) [25, 26]. The *R*B–I value of HAp/gelatin‐ coated samples is the same as that of HAp (gray and white bars in (A‐2) and (B‐2)), and we did not find a positive effect of the addition to HAp on the osteoconductivity, or any negative effects within the limit of gelatin content used. In the HAp/collagen films (C‐2), osteoconduc‐ tivity was improved, and maximum *R*B–I was obtained when the collagen content was the same as that in natural bone. The addition of too much collagen, exceeding that amount of collagen

Hydroxyapatite Coating on Titanium Implants Using Hydroprocessing and Evaluation of their Osteoconductivity 295

content in natural bone, inhibited the improvement of the osteoconductivity [33].

for osteoconductivity has not been adequately established.

The inside of the human body is equivalent to a water environment atroom temperature, since the water content in the body is about 60%. It is thought that hydroformed HAp has greater osteoconductivity than HAp synthesized using pyroprocessing, because synthesized HAp in the aqueous solution at neutral pH and room temperature is similarto that formed in the body. In addition, titanium dioxide, TiO2, which does not exist in the human body, is a remarkable compound with respect to its osteoconductivity. It is important to research and improve the osteoconductivity of substances such as HAp, TiO2, and CaTiO3. However, we need to pay attention to the properties of their compounds, such as surface roughness [35], crystallinity, and corrosivity, all of which influence osteoconductivity. Furthermore,the evaluation criterion

The development of implants with high functionality is an important problem that urgently needs to be solved, instead of merely making progress in medical technology. It is thought that nothing can compete with such implants in the progress and development of the individual technology. We hope that these important problems can be solved using the combination of the discovery of new bioactive compounds (organic and inorganic) and their coating techni‐ ques, alloy designs for the implants, and/or the growth of related surrounding techniques for

**4. Conclusion**

them.
