**3. Bioactive titanium dioxide coating on polyetheretherketone for spinal implant application**

#### **3.1. Background**

Orthopedic implants have become one of the most highly developed fields in hard‐tissue replacement. Polyetheretherketone (PEEK) polymer, with its high chemical resistance, radio‐ lucency to X‐ray scanning, and low elastic modulus similar to human cancellous bone, has become a highly preferred biomaterial, providing a promising alternative to metallic implants [21]. In particular, the elastic modulus can avoid the stress shielding effect, and prevent com‐ pression fractures and osteopenia syndrome; the X‐ray radiolucency characteristic does not present a medical image shielding problem. PEEK can also be sterilized and shaped by machining to fit the contour of bones [22]. Consequently, PEEK has been widely used for load‐bearing orthopedic applications, including dental implants, screws, and spinal inter‐ body fusion cages [23, 24].

Despite these excellent properties, PEEK is still categorized as a bioinert material because of its hydrophobic feature and inertness with the surrounding tissue [21]. To overcome this problem, two primary strategies, bulk modification and surface modification, have been proposed to enhance the bone fusion ability of the PEEK. Bulk modification incorporates various bioactive materials, such as hydroxyapatite (HA) [25], strontium‐containing hydroxyapatite [26], β‐tri‐ calcium phosphate [27], or TiO2 [28], into the PEEK matrix to form PEEK‐based biocomposites. However, their tensile strength and toughness decrease as more of the bioactive materials are added, resulting in a substantial increase in the elastic modulus of these biomedical compos‐ ites; the biomechanical property of these PEEK‐based biocomposites is therefore no longer similar to that of human cancellous bone [21]. Conversely, surface modification only alters the surface properties of a material, without adversely affecting its bulk properties. In other words, surface modification is a more suitable approach for adapting PEEK to be used as implant. Consequently, various surface modification approaches have been developed to promote the hydrophilic and biological characteristics of PEEK, such as using plasma treatment to change the surface chemistry [29], using chemical treatment to graft functional groups [30], and using laser treatment to roughen the surface [31]. Moreover, adding a functional coating to PEEK to create a bioactive surface is a more effective method for enhancing osseointegration perfor‐ mance [32–38]. Functional coating materials include HA [32], titanium [33, 34], TiO2 [35–37], and diamond‐like carbon [38]. To date, by taking the advantage of good biocompatibility of titanium with human body, very thick titanium produced over PEEK surface via vacuum plasma spray for spinal implant has been clinically available.

It has been well established that under humid conditions, the surface of TiO2 generates hydroxyl groups (─OH<sup>−</sup> ), followed by the conjunction with calcium ions (Ca2+) and phos‐ phate groups (PO4 3−) from physiological fluid. Therefore, bone‐like apatite compounds can be formed on the TiO2 surface to induce osteoblast cell adhesion and proliferation [39, 40]. Based on the results, TiO2 has been reported to exhibit excellent biocompatibility and further classified as a bioactive material [39, 40]. Furthermore, TiO2 demonstrated excellent osseointe‐ gration ability, according to the animal experiment study [41]. These biological characteristics render TiO2 film an even more promising material for the successful modification of PEEK surfaces, in comparison with regular titanium film.

In this research, the AIP technique was used to deposit TiO2 films with controllable A‐TiO<sup>2</sup> and rutile (R‐TiO2 ) phases onto PEEK substrates. The investigation focused on determining the effects of introducing a TiO<sup>2</sup> coating on the *in vitro* and *in vivo* characteristics of TiO2 ‐coated PEEK specimens, and evaluating the ability of the modified PEEK in a clinical application to shorten the osseointegration period for spinal implants and bone tissues.

#### **3.2. Preparation of biocompatible TiO2 films**

specimens. Once the specimens had been coated with TiO2

In summary, the research results show that A‐TiO2

bacteria under the photocatalytic action of A‐TiO2

, respectively. Notably, TiO2

and its inertness in corrosive environments (e.g., a sodium chloride solution) helps reduce the tendency and rate of substrate dissolution and species coating in an electrolyte. This increases the corrosive potential and decreases the corrosive current, as noted herein.

to stainless steel. The key to providing efficient antimicrobial efficacy lies in the photocatalytic performance of the coating, which originates from the anatase phase. Furthermore, based on the TEM observation results, the antimicrobial mechanisms that inhibit *S. aureus* and *E. coli*

all rate of corrosion and increases the corrosion barrier, compared with the features of bare

**3. Bioactive titanium dioxide coating on polyetheretherketone for spinal** 

Orthopedic implants have become one of the most highly developed fields in hard‐tissue replacement. Polyetheretherketone (PEEK) polymer, with its high chemical resistance, radio‐ lucency to X‐ray scanning, and low elastic modulus similar to human cancellous bone, has become a highly preferred biomaterial, providing a promising alternative to metallic implants [21]. In particular, the elastic modulus can avoid the stress shielding effect, and prevent com‐ pression fractures and osteopenia syndrome; the X‐ray radiolucency characteristic does not present a medical image shielding problem. PEEK can also be sterilized and shaped by machining to fit the contour of bones [22]. Consequently, PEEK has been widely used for load‐bearing orthopedic applications, including dental implants, screws, and spinal inter‐

Despite these excellent properties, PEEK is still categorized as a bioinert material because of its hydrophobic feature and inertness with the surrounding tissue [21]. To overcome this problem, two primary strategies, bulk modification and surface modification, have been proposed to enhance the bone fusion ability of the PEEK. Bulk modification incorporates various bioactive materials, such as hydroxyapatite (HA) [25], strontium‐containing hydroxyapatite [26], β‐tri‐

However, their tensile strength and toughness decrease as more of the bioactive materials are added, resulting in a substantial increase in the elastic modulus of these biomedical compos‐ ites; the biomechanical property of these PEEK‐based biocomposites is therefore no longer similar to that of human cancellous bone [21]. Conversely, surface modification only alters the surface properties of a material, without adversely affecting its bulk properties. In other words, surface modification is a more suitable approach for adapting PEEK to be used as implant. Consequently, various surface modification approaches have been developed to promote the

[28], into the PEEK matrix to form PEEK‐based biocomposites.

against *E. coli* is more thorough. The A‐TiO2

were −0.42 V and 1.0 × 10−8 A/cm2

efficacy of A‐TiO<sup>2</sup>

110 Application of Titanium Dioxide

**implant application**

body fusion cages [23, 24].

calcium phosphate [27], or TiO2

stainless steel.

**3.1. Background**

, the *E*corr and *I*corr of the specimens

adds effective antimicrobial characteristics

are different; specifically, the antimicrobial

coating also reduces the over‐

is an inorganic compound,

The detailed AIP‐TiO2 deposition work is described in Section 2.2. The deposition conditions used in this section are listed in **Table 1**; target current and substrate bias were systematically manipulated to achieve specific ratios of A‐TiO<sup>2</sup> and R‐TiO2 in the deposited films, character‐ ized by a fixed 100% oxygen pressure of 0.5 Pa and a cathode target voltage of 20 V.

Based on the microstructure characteristics results [12], the AIP process can successfully fabricate TiO2 films of varying A‐TiO<sup>2</sup> and R‐TiO2 composition when appropriate coating parameters are used. Specifically, the A‐TiO<sup>2</sup> phase in the deposited films ranged from 9.1% to 92.7% (**Table 1**).


**Table 1.** Deposition conditions and the proportions of A‐TiO2 phases for TiO2 coatings. A low target current promotes the growth of A‐TiO2 , whereas a high substrate bias induces the formation of R‐TiO2 . The mechanism behind this outcome was previously investigated [12].

#### **3.3.** *In vitro* **characteristics of TiO2 ‐coated PEEK**

First, the MC3T3‐E1 osteoblast cell line was used in the osteoblast compatibility test to assess the cell adhesion test, cell proliferation test, cell differentiation test, and osteogenesis perfor‐ mance [namely quantification of osteopontin (OPN), osteocalcin (OCN), and calcium content]. Next, the cell morphology that had attached to the PEEK and TiO<sup>2</sup> ‐coated PEEK specimens was observed using field emission scanning electron microscopy (FESEM; Hitachi S‐4800).

**Figure 6** shows the osteoblast cell adhesion ability, cell proliferation ability, cell differentiation ability, and osteogenesis performance on the PEEK and TiO2 ‐coated PEEK specimens at various deposition conditions [36]. Notably, the osteoblast cell adhesion, proliferation, and differentia‐ tion abilities on TiO2 ‐coated PEEK specimens were superior to the bare PEEK specimens for all of the deposition conditions. This indicates that all of the obtained TiO2 coatings possessed cell induction capabilities, which led to accelerated cell adhesion and growth and increased cell proliferation and maturity. These three indicators confirmed the osteoblast compatibility of the TiO2 ‐coatings deposited on PEEK. Furthermore, the osteogenesis performance (revealed by OPN, OCN, and calcium content as shown in **Figure 6(d)**–**(f)** [36], respectively) demonstrated that TiO2 coatings also significantly increased the osteogenesis performance. This suggests that TiO2 coatings enhance extracellular bone matrix growth. **Figure 6** [36] also shows that the speci‐ men 90A30V, which was the richest in R‐TiO<sup>2</sup> phase, exhibited the most osteoblast compatibility.

**Figure 7** shows the morphologies of the osteoblast cells after they were cultured for 0.5 and 48 h on PEEK and TiO<sup>2</sup> ‐coated PEEK specimens at different deposition conditions [36].

**Figure 6.** (a) Cell adhesion ability, (b) cell proliferation ability, (c) cell differentiation ability, (d) OPN, (e) OCN, and (f) calcium content of the osteoblast inoculated on bare PEEK and TiO2 ‐coated PEEK specimens with various deposition conditions [36].

Anticorrosive, Antimicrobial, and Bioactive Titanium Dioxide Coating for Surface-modified Purpose... http://dx.doi.org/10.5772/intechopen.68854 113

A low target current promotes the growth of A‐TiO2

formation of R‐TiO2

112 Application of Titanium Dioxide

tion abilities on TiO2

48 h on PEEK and TiO<sup>2</sup>

the TiO2

that TiO2

conditions [36].

TiO2

**3.3.** *In vitro* **characteristics of TiO2**

, whereas a high substrate bias induces the

‐coated PEEK specimens

coatings possessed

‐coated PEEK specimens at various

phase, exhibited the most osteoblast compatibility.

‐coated PEEK specimens with various deposition

. The mechanism behind this outcome was previously investigated [12].

‐coated PEEK specimens were superior to the bare PEEK specimens for

‐coated PEEK specimens at different deposition conditions [36].

**‐coated PEEK**

Next, the cell morphology that had attached to the PEEK and TiO<sup>2</sup>

all of the deposition conditions. This indicates that all of the obtained TiO2

ability, and osteogenesis performance on the PEEK and TiO2

men 90A30V, which was the richest in R‐TiO<sup>2</sup>

calcium content of the osteoblast inoculated on bare PEEK and TiO2

First, the MC3T3‐E1 osteoblast cell line was used in the osteoblast compatibility test to assess the cell adhesion test, cell proliferation test, cell differentiation test, and osteogenesis perfor‐ mance [namely quantification of osteopontin (OPN), osteocalcin (OCN), and calcium content].

was observed using field emission scanning electron microscopy (FESEM; Hitachi S‐4800).

**Figure 6** shows the osteoblast cell adhesion ability, cell proliferation ability, cell differentiation

deposition conditions [36]. Notably, the osteoblast cell adhesion, proliferation, and differentia‐

cell induction capabilities, which led to accelerated cell adhesion and growth and increased cell proliferation and maturity. These three indicators confirmed the osteoblast compatibility of

OPN, OCN, and calcium content as shown in **Figure 6(d)**–**(f)** [36], respectively) demonstrated

**Figure 7** shows the morphologies of the osteoblast cells after they were cultured for 0.5 and

**Figure 6.** (a) Cell adhesion ability, (b) cell proliferation ability, (c) cell differentiation ability, (d) OPN, (e) OCN, and (f)

‐coatings deposited on PEEK. Furthermore, the osteogenesis performance (revealed by

coatings also significantly increased the osteogenesis performance. This suggests that

coatings enhance extracellular bone matrix growth. **Figure 6** [36] also shows that the speci‐

**Figure 7.** Morphologies of the osteoblasts cultured for 0.5 and 48 h on (a) the bare PEEK specimens, and the TiO2 ‐coated PEEK specimens at different deposition conditions: (b) 60A0V, (c) 90A0V, (d) 90A20V, (e) 90A25V, and (f) 90A30V [36].

Specifically, the morphology of osteoblast cells on the bare PEEK specimens remained spheri‐ cal without the appearance of filopodium, suggesting the poor adhesion to the specimen. By comparison, osteoblasts on the TiO2 ‐coated PEEK specimens with the culturing time of 0.5 h showed a very comfortable adhesion features, that is, the filopodia extension and well‐devel‐ oped lamellipodia on the cells; this was particularly notable on the films with high ratios of R‐TiO2 to A‐TiO2 . Similar results were observed in the cells cultured for 48 h. Overall, these results further confirm that a deposited film with high R‐TiO<sup>2</sup> content has superior osteoblast growth.

Furthermore, bare PEEK, and TiO2 ‐coated PEEK specimens were then immersed in a simu‐ lated body fluid (SBF) for 1, 3, 7, 14, and 28 days, to investigate the effect of TiO<sup>2</sup> coating on the ability to induce HA formation. The TiO2 coatings that possessed A‐TiO2 and R‐TiO2 under the deposition conditions of 60A0V and 90A30V, respectively, were examined. This biomi‐ metic immersion test is a valuable approach for evaluating bioactivity of a candidate bone implant material prior to an *in vivo* test [42].

**Figure 8** illustrates the X‐ray diffraction (XRD) patterns of bare PEEK, A‐TiO<sup>2</sup> ‐coated PEEK, and R‐TiO2 ‐coated PEEK specimens after immersion in the SBF for a varying number of days [43]. During the early immersion period, the diffraction peaks that are ascribed to PEEK showed no observable change, indicating that the growing layer was undetectable in all of the specimens. After 28 days of immersion, weak and broadened diffraction peaks that are ascribed to HA were found, as shown in **Figure 8(a)** [43]. This implies that a very poor crys‐ talline or even amorphous calcium phosphate layer had formed on the PEEK specimens. By contrast, after only 7 days and 3 days of immersion in the SBF solution, diffraction peaks that are ascribed to HA could be observed in A‐TiO2 ‐ and R‐TiO2 ‐coated PEEK specimens, respec‐ tively. Over time, the intensity of these diffraction peaks increased significantly, as shown in **Figure 8(b)** and **(c)** [43], suggesting that additional crystalline HA was formed on them.

**Figure 8.** XRD patterns of the (a) bare PEEK, (b) A‐TiO<sup>2</sup> ‐coated PEEK, and (c) R‐TiO2 ‐coated PEEK specimens immersed in a SBF for 1, 3, 7, 14, and 28 days [43].

Overall, these results suggest that HA growth in a SBF solution can be enhanced by adopting TiO2 coatings, and that the R‐TiO2 coating seems to exhibit a superior capability to induce HA formation. Therefore, the results of the biomimetic immersion tests agree well with the find‐ ing of *in vitro* characteristics from osteoblast compatibility tests.

#### **3.4.** *In vivo* **characteristics of TiO2 ‐coated PEEK**

Specifically, the morphology of osteoblast cells on the bare PEEK specimens remained spheri‐ cal without the appearance of filopodium, suggesting the poor adhesion to the specimen. By

showed a very comfortable adhesion features, that is, the filopodia extension and well‐devel‐ oped lamellipodia on the cells; this was particularly notable on the films with high ratios of

the deposition conditions of 60A0V and 90A30V, respectively, were examined. This biomi‐ metic immersion test is a valuable approach for evaluating bioactivity of a candidate bone

[43]. During the early immersion period, the diffraction peaks that are ascribed to PEEK showed no observable change, indicating that the growing layer was undetectable in all of the specimens. After 28 days of immersion, weak and broadened diffraction peaks that are ascribed to HA were found, as shown in **Figure 8(a)** [43]. This implies that a very poor crys‐ talline or even amorphous calcium phosphate layer had formed on the PEEK specimens. By contrast, after only 7 days and 3 days of immersion in the SBF solution, diffraction peaks that

tively. Over time, the intensity of these diffraction peaks increased significantly, as shown in **Figure 8(b)** and **(c)** [43], suggesting that additional crystalline HA was formed on them.

‐coated PEEK specimens after immersion in the SBF for a varying number of days

‐ and R‐TiO2

‐coated PEEK, and (c) R‐TiO2

. Similar results were observed in the cells cultured for 48 h. Overall, these

coatings that possessed A‐TiO2

‐coated PEEK specimens with the culturing time of 0.5 h

‐coated PEEK specimens were then immersed in a simu‐

content has superior osteoblast

and R‐TiO2

‐coated PEEK specimens, respec‐

‐coated PEEK specimens immersed

coating on the

‐coated PEEK,

under

comparison, osteoblasts on the TiO2

Furthermore, bare PEEK, and TiO2

ability to induce HA formation. The TiO2

implant material prior to an *in vivo* test [42].

are ascribed to HA could be observed in A‐TiO2

**Figure 8.** XRD patterns of the (a) bare PEEK, (b) A‐TiO<sup>2</sup>

in a SBF for 1, 3, 7, 14, and 28 days [43].

results further confirm that a deposited film with high R‐TiO<sup>2</sup>

lated body fluid (SBF) for 1, 3, 7, 14, and 28 days, to investigate the effect of TiO<sup>2</sup>

**Figure 8** illustrates the X‐ray diffraction (XRD) patterns of bare PEEK, A‐TiO<sup>2</sup>

to A‐TiO2

114 Application of Titanium Dioxide

R‐TiO2

growth.

and R‐TiO2

Bullet‐shaped PEEK implants with a diameter of φ 4.0 mm × L 6.0 mm were used in an ani‐ mal experiment. Bare PEEK, A‐TiO2 ‐coated PEEK, and R‐TiO2 ‐coated PEEK implants were inserted into the femurs of New Zealand white male rabbits to evaluate the *in vivo* osseointe‐ gration capacity through the push‐out test and histological observation.

The push‐out test can precisely quantify the degree of fixation between an implant and bone tissues [44]. **Figure 9** shows the push‐out test results for the three implants after 4, 8, and 12 weeks [37]. Notably, the shear strength between the bone tissues and the implant increased as implantation time increased; at 12 weeks, the shear strength of the bare, A‐TiO<sup>2</sup> ‐coated, and R‐TiO2 ‐coated PEEK implants was 2.54 MPa, 3.02 MPa, and 6.51 MPa, respectively. It was thus concluded that the bare PEEK implant had the poorest shear strength, but this could be enhanced by adding a TiO2 coating. Overall, the R‐TiO2 coating had the optimal fixation.

To identify the failure mode between the implant and bone tissues after the push‐out test, FESEM was adopted to observe the fracture morphology of the implant surface at 12 weeks, as shown in **Figure 10** [37]. It was noted that new bone tissue had fully peeled off the surface

**Figure 9.** Shear strength between bone tissues and mplant for the (a) bare PEEK implant, (b) A‐TiO2 ‐coated PEEK implant, and (c) R‐TiO2 ‐coated PEEK implant at 4, 8, and 12 weeks after implantation [37].

**Figure 10.** Fracture morphology of the (a) bare PEEK implant, (b) A‐TiO2 ‐coated PEEK implant, and (c) R‐TiO2 ‐coated PEEK implant with (d) the composition analysis of its bone tissues and implant interface after the push‐out test conducted at 12 weeks [37].

of the bare PEEK implant (**Figure 10(a)** [37]), indicating that failure occurred at the bone/PEEK interface. Thus, the osseointegration capacity of a bare PEEK implant is poor. By contrast, when a TiO2 coating was applied to the implant, a large area of the residual bone tissue adhered to the surface of the implant (**Figure 10(b)** and **(c)** [37]). Additionally, a particularly large amount of residual bone tissue on the R‐TiO2 ‐coated PEEK implant surface was confirmed by elemental mapping, as revealed in **Figure 10(d)** [37]. These analytical results indicate that TiO2 ‐coated implants have a superior ability to induce bone growth and achieve bone ingrowth. The A‐ TiO2 ‐coated PEEK implants experienced some coating detachment, resulting in a mixed adhe‐ sive failure between the A‐TiO2 coating and PEEK substrate, as well as cohesive failure of the bone itself. However, the R‐TiO2 ‐coated PEEK implant surfaces were almost completely cov‐ ered with new bone tissue, almost no film detachment from the implants was observed, and thus, the failure can be regarded as cohesive failure by the bone tissue itself.

**Figure 11** depicts the histological sections of the three implants at 4, 8, and 12 weeks after implantation [37]. Notably, new bone tissue that was generated by bone remodeling had formed mature lamellar bone, and directly connected to the TiO2 ‐coated PEEK implants after 4 weeks, indicating excellent osseointegration performance. Thus, it was concluded that Anticorrosive, Antimicrobial, and Bioactive Titanium Dioxide Coating for Surface-modified Purpose... http://dx.doi.org/10.5772/intechopen.68854 117

**Figure 11.** Histological sections of the bare PEEK implant, A‐TiO2 ‐coated PEEK implant, and R‐TiO2 ‐coated PEEK implant at 4, 8, and 12 weeks after implantation [37].

of the bare PEEK implant (**Figure 10(a)** [37]), indicating that failure occurred at the bone/PEEK interface. Thus, the osseointegration capacity of a bare PEEK implant is poor. By contrast, when

PEEK implant with (d) the composition analysis of its bone tissues and implant interface after the push‐out test

implants have a superior ability to induce bone growth and achieve bone ingrowth. The A‐

ered with new bone tissue, almost no film detachment from the implants was observed, and

**Figure 11** depicts the histological sections of the three implants at 4, 8, and 12 weeks after implantation [37]. Notably, new bone tissue that was generated by bone remodeling had

after 4 weeks, indicating excellent osseointegration performance. Thus, it was concluded that

‐coated PEEK implants experienced some coating detachment, resulting in a mixed adhe‐

mapping, as revealed in **Figure 10(d)** [37]. These analytical results indicate that TiO2

thus, the failure can be regarded as cohesive failure by the bone tissue itself.

formed mature lamellar bone, and directly connected to the TiO2

 coating was applied to the implant, a large area of the residual bone tissue adhered to the surface of the implant (**Figure 10(b)** and **(c)** [37]). Additionally, a particularly large amount of

‐coated PEEK implant surface was confirmed by elemental

‐coated PEEK implant, and (c) R‐TiO2

coating and PEEK substrate, as well as cohesive failure of the

‐coated PEEK implant surfaces were almost completely cov‐

‐coated

‐coated

‐coated PEEK implants

a TiO2

TiO2

residual bone tissue on the R‐TiO2

conducted at 12 weeks [37].

116 Application of Titanium Dioxide

**Figure 10.** Fracture morphology of the (a) bare PEEK implant, (b) A‐TiO2

sive failure between the A‐TiO2

bone itself. However, the R‐TiO2

TiO2 coating exhibits strong osteoblast compatibility and rapidly activates bone remodeling. Subsequently, the coating induced adhesion and proliferation of osteoblasts on the implant surface, and differentiation into osteocytes for the production of new bone tissue and later bone bonding. Conversely, new lamellar bone on the surface of the bare PEEK implants was not completely mature and not fully bonded with the implant.

The response of the TiO2 ‐coated PEEK implants in the marrow cavity (located far from the cortical bone) at 4 weeks indicated that regenerated bone tissues grew onto the implant sur‐ faces; moreover, this new bone is the result of bone tissue repair, which proliferates from the endosteum of cortical bone. Due to the osteoconductive effect, the new bone tissues grew inward to the implant surfaces in the marrow [45]. These findings indicate that TiO<sup>2</sup> coatings have excellent osteoconductivity and promote new bone growth on the TiO2 ‐coated PEEK implant surfaces, with connections to cortical bone. By contrast, the surfaces of the bare PEEK implant were covered with fibrous tissue, implying that bone bonding did not occur between the implant and the cortical bone. Fibrous tissue growth is likely caused by micro movement in the implant and poor stability during the early implantation period [46].

When the implant period was extended to 8 weeks, immature osteogenesis was observed in the cortical bone around the bare PEEK implant, and new bone tissue was maturing after 12 weeks. However, fibrous tissue was still identified at the interface between the implants and bone tissues, indicating that the osseointegration capacity of bare PEEK implants is very limited, even when the implantation period is extended. By contrast, 8 weeks after the implan‐ tation of the TiO2 ‐coated PEEK implants, histological sections in the marrow cavity revealed that the new bone tissue was maturing and osteocytes covered the their surface. In other words, the osteoconductive effect of TiO<sup>2</sup> coating triggers quick bone remodeling. The new bone was fully mature and closely integrated with the TiO2 coating in the cavity after 12 weeks (**Figure 11** [37]). However, a comparison of the TiO2 coatings with different phase structures indicated that the degree of bone bonding between new bone and the R‐TiO2 ‐coated PEEK implant was significantly better than that between new bone and the A‐TiO<sup>2</sup> ‐coated PEEK implant. In addition, some gaps existed between the A‐TiO2 coating and the new bone in some areas; detachment of the A‐TiO2 coating was also noted.

In summary, the *in vitro* and *in vivo* characteristics can be improved by TiO2 coating because of its bioactivity; R‐TiO2 coatings perform particularly well, promoting biomimetic HA growth, osteoblast compatibility, and osseointegration. These phenomena are attributable to the abun‐ dance of negatively charged hydroxyl groups on the R‐TiO2 surface [35–37].
