**Biomimetic Porous Bone-Like Apatite Coatings on Metals, Organic Polymers and Microparticles Metals, Organic Polymers and Microparticles**

**Biomimetic Porous Bone-Like Apatite Coatings on** 

DOI: 10.5772/intechopen.71390

Takeshi Yabutsuka Additional information is available at the end of the chapter

Takeshi Yabutsuka

[21] Zhou K et al. Porous hydroxyapatite ceramics fabricated by an ice-templating method.

[22] Julbe A, Farrusseng D, Guizard C. Porous ceramic membranes for catalytic reactors—

[23] Wu P et al. A review of preparation techniques of porous ceramic membranes. Journal

[24] Bowen C et al. Processing and properties of porous piezoelectric materials with high hydrostatic figures of merit. Journal of the European Ceramic Society. 2004;**24**(2):541-545

[25] Li H, Tian C, Deng ZD. Energy harvesting from low frequency applications using piezo-

[26] Zhang Y et al. Enhanced pyroelectric and piezoelectric properties of PZT with aligned porosity for energy harvesting applications. Journal of Materials Chemistry A. 2017;

overview and new ideas. Journal of Membrane Science. 2001;**181**(1):3-20

Scripta Materialia. 2011;**64**(5):426-429

**5**(14):6569-6580

10 Recent Advances in Porous Ceramics

of Ceramic Processing Research. 2015;**16**:102-106

electric materials. Applied physics reviews. 2014;**1**(4):041301

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.71390

#### **Abstract**

When pH and temperature of simulated body fluid (SBF) are raised, fine particles of calcium phosphate are precipitated. Recently, the authors' research group found that these fine particles were highly active to induce formation of porous bone-like apatite in SBF, or body fluid, and named them 'apatite nuclei.' By using apatite nuclei, the author successfully imparted high bioactivity, that is, apatite-forming ability, to various kinds of bioinert biomaterials such as metals and organic polymers in a series of recent studies. These materials spontaneously formed porous bone-like apatite layer on their surfaces in SBF in a short time and showed high bioactivity in vitro. In addition, thWe author also successfully fabricated microcapsules consisted of porous bone-like apatite by using apatite nuclei.

**Keywords:** porous bone-like apatite, apatite nuclei, bioactive metals, bioactive organic polymers, apatite microcapsules

#### **1. Introduction**

#### **1.1. Bioactive materials**

When artificial materials such as metals, ceramics and organic polymers are implanted in the body, these materials are generally encapsulated with noncalcified fibrous tissue and separated from the surrounding living tissue. Such biological response is known as a normal immune reaction of the living body with respect to exogenous materials. In early 1970s, L.L. Hench found that Na<sup>2</sup> O-CaO-SiO<sup>2</sup> -P2 O5 -type glass (bioglass®) showed bone-bonding ability without the isolation from surrounding living tissue [1]. Since the discovery of bioglass®, ceramic materials such as glass-ceramic Ceravital® containing crystalline apatite [2], sintered

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hydroxyapatite (Ca10(PO<sup>4</sup> ) 6 (OH)<sup>2</sup> ) [3], glass-ceramics Cerabone® A-W containing crystalline apatite and wollastonite (CaO·SiO<sup>2</sup> ) [4, 5], and so on have been found to bond with living bone. Most of the ceramics mentioned above forms apatite layer on their surface and can bond with living bone through the apatite layer in living body [6, 7]. This apatite layer consists of minute crystallites containing carbonate ions in chemical composition [8] and is similar to apatite, which contains living bone [9, 10]. On the apatite layer, osteoblast actively proliferates and differentiates [6, 11]. Hence, bone tissue is formed on the apatite layer and the artificial materials can be also found to bond with the surrounding bone tissue through the apatite layer. Such material property is often defined as 'bioactivity' in the research field of ceramic biomaterials.

#### **1.2. Simulated body fluid**

In early 1990s, T. Kokubo proposed an acellular simulated body fluid (SBF) with ion concentrations similar to those of human blood plasma [12–14]. It is possible to reproduce the abovementioned apatite formation reaction on most of the bioactive materials by soaking the materials in SBF. Hence, we can predict bioactivity, that is, apatite-forming ability, of specimens by soaking them in SBF and evaluating apatite formation on their surface. **Table 1** shows the ion concentrations of simulated body fluid and human blood plasma. The SBF can be prepared by dissolving NaCl, NaHCO<sup>3</sup> , KCl, K<sup>2</sup> HPO4 ·3H<sup>2</sup> O, MgCl<sup>2</sup> ·6H<sup>2</sup> O, CaCl<sup>2</sup> and Na<sup>2</sup> SO<sup>4</sup> in pure water and maintaining the pH value at 7.40 with (CH<sup>2</sup> OH)<sup>3</sup> CNH<sup>2</sup> and 1 mol dm−3 HCl solution at 36.5°C. The details of preparation method of SBF and the bioactivity test are certified by ISO 23317 [14]

#### **1.3. Apatite nuclei**

When pH and temperature of SBF are raised, fine particles of calcium phosphate are precipitated. Generally, calcium phosphate formation in an aqueous solution can be described as shown in (Eq. (1)) by applying hydroxyapatite as a representative calcium phosphate.


$$10\,\text{Ca}^{2+} + 6\text{PO}\_4^{3-} + 2\text{OH}^- = \text{Ca}\_{\text{10}}\text{(PO}\_4\text{)}\_6\text{(OH)}\_2\tag{1}$$

When pH value or concentration of the aqueous solution increases, apatite formation is promoted from a viewpoint of the abovementioned chemical equilibrium because of an increase of

ment because of an increase of chemical reaction rate of calcium phosphate formation. Yao et al. found that thus-precipitated fine particles of calcium phosphate showed high activity for induction of porous bone-like apatite formation in SBF and named the particles 'apatite nuclei' [15].

As described in Section 1.3, apatite nuclei, precipitated by raising pH or temperature of SBF, actively induce apatite formation in SBF or body environment. By using apatite nuclei, excellent implant materials possessing various mechanical properties as well as high bioactivity and bioaffinity can be developed by combining it with various kinds of bioinert materials such as metals and organic polymers. Recently, we found that high apatite-forming ability

• Micropores are formed on the surface of the substrate by acid treatment or sandblasting

• The abovementioned micropores-formed substrate or porous substrate is soaked in SBF, and pH and temperature of SBF is increased. By this treatment, apatite nuclei are precipi-

When this material is implanted into a bone defect, it is thought that apatite nuclei induce apatite formation and this material subsequently bonds with living bone through the formed bone-like apatite layer (**Figure 1**). As a result, it is expected that the materials can bond with

**2. Fabrication of bioactive metals by incorporation of apatite nuclei as** 

Metals have high mechanical strength and high fracture toughness. Among them, stainless used steel (SUS), cobalt-chromium (Co-Cr) alloys, titanium (Ti) and its alloys have

**1.4. Bioactive materials' design by utilizing the function of apatite nuclei**

**Figure 1.** Bioactive materials' design by utilizing the function of apatite nuclei.

3−. In addition, the reaction is accelerated under high-temperature environ-

Biomimetic Porous Bone-Like Apatite Coatings on Metals, Organic Polymers and Microparticles

http://dx.doi.org/10.5772/intechopen.71390

13

OH<sup>−</sup>

process.

or Ca2+ and PO4

can be imparted by the following method [16].

tated in the pores of the substrate.

**precursors of apatite**

**2.1. Bioactive metals**

living bone through the formed apatite layer.

**Table 1.** Ion concentrations of simulated body fluid (SBF) and human blood plasma.

Biomimetic Porous Bone-Like Apatite Coatings on Metals, Organic Polymers and Microparticles http://dx.doi.org/10.5772/intechopen.71390 13

**Figure 1.** Bioactive materials' design by utilizing the function of apatite nuclei.

hydroxyapatite (Ca10(PO<sup>4</sup>

12 Recent Advances in Porous Ceramics

**1.2. Simulated body fluid**

are certified by ISO 23317 [14]

10 Ca2+ + 6PO4

**Ion Ion concentration/mM**

Na<sup>+</sup> 142.0 142.0 K<sup>+</sup> 5.0 5.0 Mg2+ 2.5 2.5 Ca2+ 1.5 1.5 Cl<sup>−</sup> 147.8 103.0

<sup>−</sup> 4.2 27.0

2− 1.0 1.0

**Table 1.** Ion concentrations of simulated body fluid (SBF) and human blood plasma.

2− 0.5 0.5

**1.3. Apatite nuclei**

biomaterials.

Na<sup>2</sup> SO<sup>4</sup>

HCO3

HPO4

SO<sup>4</sup>

apatite and wollastonite (CaO·SiO<sup>2</sup>

)6 (OH)<sup>2</sup>

can be prepared by dissolving NaCl, NaHCO<sup>3</sup>

) [3], glass-ceramics Cerabone® A-W containing crystalline

bone. Most of the ceramics mentioned above forms apatite layer on their surface and can bond with living bone through the apatite layer in living body [6, 7]. This apatite layer consists of minute crystallites containing carbonate ions in chemical composition [8] and is similar to apatite, which contains living bone [9, 10]. On the apatite layer, osteoblast actively proliferates and differentiates [6, 11]. Hence, bone tissue is formed on the apatite layer and the artificial materials can be also found to bond with the surrounding bone tissue through the apatite layer. Such material property is often defined as 'bioactivity' in the research field of ceramic

In early 1990s, T. Kokubo proposed an acellular simulated body fluid (SBF) with ion concentrations similar to those of human blood plasma [12–14]. It is possible to reproduce the abovementioned apatite formation reaction on most of the bioactive materials by soaking the materials in SBF. Hence, we can predict bioactivity, that is, apatite-forming ability, of specimens by soaking them in SBF and evaluating apatite formation on their surface. **Table 1** shows the ion concentrations of simulated body fluid and human blood plasma. The SBF

dm−3 HCl solution at 36.5°C. The details of preparation method of SBF and the bioactivity test

When pH and temperature of SBF are raised, fine particles of calcium phosphate are precipitated. Generally, calcium phosphate formation in an aqueous solution can be described as

<sup>3</sup><sup>−</sup> + 2OH<sup>−</sup> = Ca<sup>10</sup> (PO4)

**SBF Blood plasma**

shown in (Eq. (1)) by applying hydroxyapatite as a representative calcium phosphate.

in pure water and maintaining the pH value at 7.40 with (CH<sup>2</sup>

, KCl, K<sup>2</sup>

HPO4

·3H<sup>2</sup>

6 (OH)

O, MgCl<sup>2</sup>

OH)<sup>3</sup>

·6H<sup>2</sup>

CNH<sup>2</sup>

<sup>2</sup> (1)

O, CaCl<sup>2</sup>

and

and 1 mol

) [4, 5], and so on have been found to bond with living

When pH value or concentration of the aqueous solution increases, apatite formation is promoted from a viewpoint of the abovementioned chemical equilibrium because of an increase of OH<sup>−</sup> or Ca2+ and PO4 3−. In addition, the reaction is accelerated under high-temperature environment because of an increase of chemical reaction rate of calcium phosphate formation. Yao et al. found that thus-precipitated fine particles of calcium phosphate showed high activity for induction of porous bone-like apatite formation in SBF and named the particles 'apatite nuclei' [15].

#### **1.4. Bioactive materials' design by utilizing the function of apatite nuclei**

As described in Section 1.3, apatite nuclei, precipitated by raising pH or temperature of SBF, actively induce apatite formation in SBF or body environment. By using apatite nuclei, excellent implant materials possessing various mechanical properties as well as high bioactivity and bioaffinity can be developed by combining it with various kinds of bioinert materials such as metals and organic polymers. Recently, we found that high apatite-forming ability can be imparted by the following method [16].


When this material is implanted into a bone defect, it is thought that apatite nuclei induce apatite formation and this material subsequently bonds with living bone through the formed bone-like apatite layer (**Figure 1**). As a result, it is expected that the materials can bond with living bone through the formed apatite layer.
