**3. Fabrication of bioactive organic polymers by incorporation of apatite nuclei as precursors of apatite**

#### **3.1. Bioactive organic polymers**

X-ray diffraction (TF-XRD) profiles of the surface of the bioactive SUS after soaking in SBF for 0 day (i.e., before soaking in SBF), 1 day, 3 days and 7 days. Before soaking in SBF, diffraction peaks of apatite were not detected. This result suggested that the calcium phosphate coating formed in the alkaline SBF treatment was consisted of amorphous calcium phosphate (ACP). After soaking in SBF for 1 day, 3 days and 7 days, diffraction peaks of apatite were clearly detected. **Figure 5** shows the SEM micrograph and the EDX profile of the surface of the bioactive SUS after soaking in SBF for 1 day. It was observed that the whole surface was covered with porous coating, which consisted of needle-like crystallites, which characterize bone-like apatite, in the SEM observation. In the EDX profile, the intensity of the peaks of P and Ca was relatively increased in comparison with those after the alkaline SBF treatment shown in **Figure 3**. From these results, it is indicated that apatite formation was induced within 1 day

**Figure 4.** TF-XRD profile of the surface of the bioactive SUS after the soaking in SBF for 0 day, 1 day, 3 days and 7 days.

**Figure 3.** (a) SEM micrograph and (b) EDX profile of the surface of the SUS plate after the alkaline SBF treatment.

16 Recent Advances in Porous Ceramics

and high bioactivity was imparted to the SUS by the alkaline SBF treatment.

Organic polymers have various mechanical properties and are easily processed in various shapes such as sticks, plates, films, sponges and fibers. Because of these properties, organic polymers have been widely used as various implant materials such as artificial hip joint, artificial knee joint, artificial knuckle joint and artificial ligament. Generally, however, organic polymers are not bioactive and cannot bond with living bone in living body. If organic polymers acquire bioactivity, implant materials with various mechanical properties as well as high bioactivity can be developed. As a conventional method to impart bioactivity to organic polymers, the method that bioactive ceramics particles such as sintered hydroxyapatite are dispersed in polymeric matrix have been mainly applied. Among them, HAPEX™, which contains 40 vol% of hydroxyapatite in high density polyethylene matrix [35], has been already in practical use as an orbital implant and a middle ear implant. However, such method is difficult to control bioactivity of the materials because most of ceramics particles are buried inside the polymeric matrix and bioactivity was performed by only the particles exposed to the surface of the materials [36]. As one of the most effective method for solving this problem, the alkaline SBF treatment described in Section 1.4 can act as an attractive candidate to impart bioactivity also to polymeric biomaterials, similar to the case of metals. Recently, the author successfully established the surface modification technique to impart bioactivity to ultrahigh-molecular weight polyethylene (UHMWPE) [37], polyethyleneterephthalate (PET) [24], poly-l-lactic acid (PLLA) [38], polyetheretherketone (PEEK) [39–41], carbon fiber-reinforced PEEK (CFR-PEEK) [42], glass fiber-reinforced PEEK (GFR-PEEK) [42] and glass fiber-reinforced poly(m-Xylyleneadipamide)-6 (GFR-MXD6) [43]. Among them, the author introduces the details of bioactive PEEK as representative cases of polymeric biomaterials in this chapter.

*3.3.2. Impartation of apatite-forming ability: incorporation of apatite nuclei as precursors of apatite*

the micropores-formed PEEK were treated with glow-discharge in O<sup>2</sup>

**Figure 6.** SEM micrograph of the surface of the PEEK plate after the sulfuric acid treatment.

alkaline SBF treatment. Hereafter, this material is denoted as 'bioactive PEEK'

**coatings in biomimetic environment**

**3.4. Apatite-forming ability of bioactive PEEK: formation of porous bone-like apatite** 

Next, bioactivity of the bioactive PEEK was evaluated by SBF test similar to the case of SUS as described in Section 2.4. **Figure 8** shows the TF-XRD profiles of the surface of the bioactive PEEK after the soaking in SBF for 0 day, 1 day, 3 days, 7 days and 14 days. After soaking in SBF for 1 day, diffraction peaks of apatite were detected. As elapse of soaking time, the intensity of the diffraction peaks increased and those of PEEK decreased. **Figure 9** shows the SEM micrograph and the EDX profile of the surface of the bioactive PEEK after soaking in SBF for 1 day. It can be seen that the whole surface of the plate was covered with porous coatings consisted of needle-like crystallites, which characterize bone-like apatite, in the SEM observation

Next, the author conducted surface modification to impart bioactivity to PEEK by incorporation of apatite nuclei. As a pretreatment for the apatite nuclei incorporation, the surfaces of

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

treatment, reactive functional groups, which have hydrophilic property, were supplied on the surfaces of organic polymers [45]. The pH value of SBF was increased to 8.4 by dissolving tris(hydroxymethyl)aminomethane at 25°C. In order to precipitate apatite nuclei in the micropores, the micropores-formed PEEK was soaked in this SBF and kept at 70°C for 24 hours. Hereafter, this treatment is denoted as 'alkaline SBF treatment'. **Figure 7** shows the SEM micrograph and the EDX profile of the surface of the micropores-formed PEEK after the alkaline SBF treatment. It can be seen that the surface morphology was different from **Figure 6**, after the sulfuric acid treatment. In the EDX profile, peaks of P and Ca were detected. In the SEM micrograph, spherical particles of apatite nuclei were observed on the whole surface. It is considered that apatite nuclei were precipitated on the surface or inside the pores by the

gas atmosphere. By this

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

19

#### **3.2. PEEK as orthopedic materials**

PEEK is well known as one of the next-generation polymeric materials with high mechanical toughness. In addition, PEEK is in the spotlight of orthopedic or dental fields because of its more similar elastic modulus with cortical bone than metallic biomaterials such as Ti alloys, SUS and Co-Cr alloys and ceramic biomaterials such as alumina, zirconia and sintered hydroxyapatite. From these mechanical properties, it is expected that PEEK becomes a candidate for replacing conventional metallic or ceramic bone substitutes in clinical use [44]. Although PEEK has biocompatibility, bioactivity of PEEK is extremely poor. If high bioactivity is imparted to PEEK, the range of its clinical or dental use such as minimally invasive orthopedic treatment will be largely extended. As described in this section, micropores were formed on PEEK by sulfuric acid treatment. Then apatite nuclei were precipitated in the pores and bioactivity was imparted to PEEK by incorporation of apatite nuclei.

#### **3.3. Fabrication process of bioactive PEEK**

#### *3.3.1. Micropores formation by sulfuric acid treatment*

First, in order to form micropores on the surface of the PEEK, PEEK plates were treated with 98% sulfuric acid at room temperature. **Figure 6** shows the SEM micrograph of the surface of the PEEK after the sulfuric acid treatment. It can be seen that cancellous micropores around 500 nm in diameter were formed on the whole surface of the plate.

Biomimetic Porous Bone-Like Apatite Coatings on Metals, Organic Polymers and Microparticles http://dx.doi.org/10.5772/intechopen.71390 19

**Figure 6.** SEM micrograph of the surface of the PEEK plate after the sulfuric acid treatment.

artificial knee joint, artificial knuckle joint and artificial ligament. Generally, however, organic polymers are not bioactive and cannot bond with living bone in living body. If organic polymers acquire bioactivity, implant materials with various mechanical properties as well as high bioactivity can be developed. As a conventional method to impart bioactivity to organic polymers, the method that bioactive ceramics particles such as sintered hydroxyapatite are dispersed in polymeric matrix have been mainly applied. Among them, HAPEX™, which contains 40 vol% of hydroxyapatite in high density polyethylene matrix [35], has been already in practical use as an orbital implant and a middle ear implant. However, such method is difficult to control bioactivity of the materials because most of ceramics particles are buried inside the polymeric matrix and bioactivity was performed by only the particles exposed to the surface of the materials [36]. As one of the most effective method for solving this problem, the alkaline SBF treatment described in Section 1.4 can act as an attractive candidate to impart bioactivity also to polymeric biomaterials, similar to the case of metals. Recently, the author successfully established the surface modification technique to impart bioactivity to ultrahigh-molecular weight polyethylene (UHMWPE) [37], polyethyleneterephthalate (PET) [24], poly-l-lactic acid (PLLA) [38], polyetheretherketone (PEEK) [39–41], carbon fiber-reinforced PEEK (CFR-PEEK) [42], glass fiber-reinforced PEEK (GFR-PEEK) [42] and glass fiber-reinforced poly(m-Xylyleneadipamide)-6 (GFR-MXD6) [43]. Among them, the author introduces the details of bioactive PEEK as representative

PEEK is well known as one of the next-generation polymeric materials with high mechanical toughness. In addition, PEEK is in the spotlight of orthopedic or dental fields because of its more similar elastic modulus with cortical bone than metallic biomaterials such as Ti alloys, SUS and Co-Cr alloys and ceramic biomaterials such as alumina, zirconia and sintered hydroxyapatite. From these mechanical properties, it is expected that PEEK becomes a candidate for replacing conventional metallic or ceramic bone substitutes in clinical use [44]. Although PEEK has biocompatibility, bioactivity of PEEK is extremely poor. If high bioactivity is imparted to PEEK, the range of its clinical or dental use such as minimally invasive orthopedic treatment will be largely extended. As described in this section, micropores were formed on PEEK by sulfuric acid treatment. Then apatite nuclei were precipitated in the pores and bioactivity was imparted to PEEK by incorporation of

First, in order to form micropores on the surface of the PEEK, PEEK plates were treated with 98% sulfuric acid at room temperature. **Figure 6** shows the SEM micrograph of the surface of the PEEK after the sulfuric acid treatment. It can be seen that cancellous micropores around

cases of polymeric biomaterials in this chapter.

**3.3. Fabrication process of bioactive PEEK**

*3.3.1. Micropores formation by sulfuric acid treatment*

500 nm in diameter were formed on the whole surface of the plate.

**3.2. PEEK as orthopedic materials**

18 Recent Advances in Porous Ceramics

apatite nuclei.

#### *3.3.2. Impartation of apatite-forming ability: incorporation of apatite nuclei as precursors of apatite*

Next, the author conducted surface modification to impart bioactivity to PEEK by incorporation of apatite nuclei. As a pretreatment for the apatite nuclei incorporation, the surfaces of the micropores-formed PEEK were treated with glow-discharge in O<sup>2</sup> gas atmosphere. By this treatment, reactive functional groups, which have hydrophilic property, were supplied on the surfaces of organic polymers [45]. The pH value of SBF was increased to 8.4 by dissolving tris(hydroxymethyl)aminomethane at 25°C. In order to precipitate apatite nuclei in the micropores, the micropores-formed PEEK was soaked in this SBF and kept at 70°C for 24 hours. Hereafter, this treatment is denoted as 'alkaline SBF treatment'. **Figure 7** shows the SEM micrograph and the EDX profile of the surface of the micropores-formed PEEK after the alkaline SBF treatment. It can be seen that the surface morphology was different from **Figure 6**, after the sulfuric acid treatment. In the EDX profile, peaks of P and Ca were detected. In the SEM micrograph, spherical particles of apatite nuclei were observed on the whole surface. It is considered that apatite nuclei were precipitated on the surface or inside the pores by the alkaline SBF treatment. Hereafter, this material is denoted as 'bioactive PEEK'

#### **3.4. Apatite-forming ability of bioactive PEEK: formation of porous bone-like apatite coatings in biomimetic environment**

Next, bioactivity of the bioactive PEEK was evaluated by SBF test similar to the case of SUS as described in Section 2.4. **Figure 8** shows the TF-XRD profiles of the surface of the bioactive PEEK after the soaking in SBF for 0 day, 1 day, 3 days, 7 days and 14 days. After soaking in SBF for 1 day, diffraction peaks of apatite were detected. As elapse of soaking time, the intensity of the diffraction peaks increased and those of PEEK decreased. **Figure 9** shows the SEM micrograph and the EDX profile of the surface of the bioactive PEEK after soaking in SBF for 1 day. It can be seen that the whole surface of the plate was covered with porous coatings consisted of needle-like crystallites, which characterize bone-like apatite, in the SEM observation

**Figure 7.** (a) SEM micrograph and (b) EDX profile of the surface of the PEEK plate after the alkaline SBF treatment.

were applied same treatments without sulfuric acid treatment. The average value of adhesion strength of the porous bone-like apatite coating for the bioactive PEEK with the pores formed by the sulfuric acid treatment was 6.7 MPa. In contrast, PEEK without pores formation was 2.1 MPa. The PEEK with pores formed by the sulfuric acid treatment presented higher adhesion strength. This difference was caused by a mechanical interlocking effect between the PEEK and porous bone-like apatite layer by existence of the micropores, similar to the case of the SUS.

**Figure 9.** (a) SEM micrograph and (b) EDX profile of the surface of the bioactive PEEK after the soaking in SBF for 1 day. The generation of cracks observed in **Figure 9** (a) was caused when the specimen was air-dried after the SBF test.

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

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

21

As described in Section 2.1, the author reported that this bioactivity method was applicable not only to PEEK but also to other kinds of polymeric biomaterials such as UHMWPE, PET, PLLA, CFR-PEEK, GFR-PEEK and GFR-MXD6 by optimizing the condition of micropores formation and apatite nuclei precipitation according to the kinds of materials, similar to the case of the metals [24, 37, 38, 42, 43]. Also in the case of these polymers, apatite formation was induced within 1 day in SBF in most cases. Hence, it is suggested that the alkaline SBF treatment was an effective method to impart high bioactivity not only to metals but also to polymeric implant materials.

**4. Fabrication of apatite microcapsules consisted of biomimetic porous bone-like apatite coatings by using apatite nuclei as precursors of apatite**

Drug delivery system (DDS) is one of the most attractive techniques in the medical and pharmaceutical fields. DDS can contributes to chemotherapy that can achieve low side effects because it can achieve an efficient local or controlled release of pharmaceutical drugs. The microcapsules can be filled with pharmaceutical drugs. Hence, the DDS carriers consisted of microcapsules have a possibility to be applied in many kinds of pharmaceutical fields. Apatite has high bioaffinity because it forms bone-like apatite coatings consisted of needle-like fine crystallites on its surface in living body and can avoid immune reaction. From the above idea, it is thought that microcapsules possessing high biocompatibility can be obtained by applying apatite. The porous bone-like

**4.1. Fabrication of microcapsule consisted of porous bone-like apatite**

apatite microcapsules can be fabricated by the following process [46, 47]:

**3.6. Case of the other types of polymers**

**Figure 8.** TF-XRD profiles of the surface of the untreated PEEK and the bioactive PEEK after the soaking in SBF for 0 day, 1 day, 3 days, 7 days and 14 days.

and peaks of P and Ca were strongly detected in the EDX analysis. By considering the results of TF-XRD, SEM and EDX, it is revealed that porous bone-like apatite, which was induced by apatite nuclei, covered the whole surface of the bioactive PEEK within 1 day and the apatite layer grew thick as elapse of the soaking time.

#### **3.5. Adhesion property of porous bone-like apatite coating formed on the bioactive PEEK**

Similar to the case of metals, adhesive strength between the bioactive PEEK and the porous bone-like apatite coating formed by soaking in SBF for 14 days was measured by a modified ASTM C-633 method [30–33]. For the reference, the author prepared the specimens, which Biomimetic Porous Bone-Like Apatite Coatings on Metals, Organic Polymers and Microparticles http://dx.doi.org/10.5772/intechopen.71390 21

**Figure 9.** (a) SEM micrograph and (b) EDX profile of the surface of the bioactive PEEK after the soaking in SBF for 1 day. The generation of cracks observed in **Figure 9** (a) was caused when the specimen was air-dried after the SBF test.

were applied same treatments without sulfuric acid treatment. The average value of adhesion strength of the porous bone-like apatite coating for the bioactive PEEK with the pores formed by the sulfuric acid treatment was 6.7 MPa. In contrast, PEEK without pores formation was 2.1 MPa. The PEEK with pores formed by the sulfuric acid treatment presented higher adhesion strength. This difference was caused by a mechanical interlocking effect between the PEEK and porous bone-like apatite layer by existence of the micropores, similar to the case of the SUS.

#### **3.6. Case of the other types of polymers**

and peaks of P and Ca were strongly detected in the EDX analysis. By considering the results of TF-XRD, SEM and EDX, it is revealed that porous bone-like apatite, which was induced by apatite nuclei, covered the whole surface of the bioactive PEEK within 1 day and the apatite

**Figure 8.** TF-XRD profiles of the surface of the untreated PEEK and the bioactive PEEK after the soaking in SBF for 0 day,

**Figure 7.** (a) SEM micrograph and (b) EDX profile of the surface of the PEEK plate after the alkaline SBF treatment.

Similar to the case of metals, adhesive strength between the bioactive PEEK and the porous bone-like apatite coating formed by soaking in SBF for 14 days was measured by a modified ASTM C-633 method [30–33]. For the reference, the author prepared the specimens, which

**3.5. Adhesion property of porous bone-like apatite coating formed on the** 

layer grew thick as elapse of the soaking time.

**bioactive PEEK**

1 day, 3 days, 7 days and 14 days.

20 Recent Advances in Porous Ceramics

As described in Section 2.1, the author reported that this bioactivity method was applicable not only to PEEK but also to other kinds of polymeric biomaterials such as UHMWPE, PET, PLLA, CFR-PEEK, GFR-PEEK and GFR-MXD6 by optimizing the condition of micropores formation and apatite nuclei precipitation according to the kinds of materials, similar to the case of the metals [24, 37, 38, 42, 43]. Also in the case of these polymers, apatite formation was induced within 1 day in SBF in most cases. Hence, it is suggested that the alkaline SBF treatment was an effective method to impart high bioactivity not only to metals but also to polymeric implant materials.
