**1. Nano-properties of titanium dioxide nanotube arrays**

Titanium dioxide (TiO2 ) nanotube arrays are also referred to as titania nanotube arrays (TNA). Nanotubes layered by anodization in particular, have garnered considerable interest in the enhancement of orthopedic procedures due to their inherent high quality and cost-effectiveness [1, 2]. The anodization process produces continuous and vertically aligned TiO2 nanotubes structure in an array form on the titanium (Ti) alloy surface as shown in **Figure 1**.

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deposited [9]. The deposition of bone-like apatite component is crucial in mediating a positive osseointegration, the interaction of implant surface with surrounding bone tissues [11, 12].

Titanium Dioxide Nanotube Arrays for Biomedical Implant Materials and Nanomedicine…

http://dx.doi.org/10.5772/intechopen.73060

Therefore, anatase crystal phase TNA has become a major interest in medical research. A study by Yu et al. [13] reported that anatase TNA could yield an optimal biological response for cell adhesion, spreading, proliferation and differentiation. TNA with 100 nm diameter have been suggested to provide similar characteristic as the natural bone topography comprising nanophase hydroxyapatite (100 nm size regime) in the collagen matrix [14, 15].

Biomaterials are the core needs in diverse medical areas such as for the orthopedic, dental, cardiovascular, and craniofacial implants [59–64]. In the past, Ti or Ti alloys were commonly used as biomaterial implants [16]. Besides having great mechanical properties and excellent corrosion resistance, titanium possesses a good biocompatibility, which related to the behav-

This metal surface is known to be cytocompatible, which refers to the ability to bind with biomolecules and supported cellular attachment (adhesion), growth and proliferation [11, 19–22].

surface. This naturally occurring oxide of titanium (Ti4+) resulted from the reduction–oxidation

to be bioactive which makes it possible to establish direct contact with bone cells and promote

To meet the expectation of successful biomedical implants, there is a critical need in reducing the post-operation healing time and safe placement of implants have become a major concern. This is because the human body has minimum time to react to osseointegration before the body starts rejecting the implants. The currently available implants possess these limitations. For instance, at the early stage of implantation of Ti implant materials into human body, the material surface cannot bind directly to living bone due to biologically inert metallic surface properties [25]. Hence, the healing period takes a longer time and sometimes the surface gets encapsulated over the time [26]. This attributes to poor osseointegration, leading to aseptic loosening of the implant, development of fibrous tissue (at interface of implant-bone), micromotion (at interface of bone implant) and/or wear debris formation (wear particles of bone implant interface) and further delamination (or fracture) between bone and implant material [26, 27].

The surface of implant materials plays a vital role in controlling osseointegration to decrease healing time; in this regard, scholars aim to improve or alter the biocompatibility of Ti implant surface for long-term clinical use [16]. Current studies focus on the potential of titania with a three-dimensional (3-D) microporous or nanoporous structure to enhance the formability of apatite (bone component) and the adherence speed of osteoblastic cells compared with that of a dense titania layer [28–30]. The nanometric scaled surface modification has shown to be

) on the

471

O) [23]. This oxidized layer of Ti is known

Conventionally, Ti alloys have a thin layer of titania also known as titanium oxide (TiO2

4−) and water (H2

**2. Potential application of TNA in biomedical implants**

ior and function of nontoxic materials in living systems [17, 18].

the formation of apatite (major component of bone tissue) [24].

critical for the tissue acceptance and cell survival.

action of surrounding oxygen (O2

**Figure 1. TNA nanomatrix observation by field emission scanning electron microscopy**. (A) The surface modification by anodization produced nanotubular structure of TiO2 layer (TNA) in vertical view and (B) nanoporous structure from top view; the formation of well-aligned nanotubular structure (nanotubes). The nanotubes were linked to each other and ripple marks occurred at the sidewalls.

Several researchers have investigated a range of parameters associated with the physical and element properties of TNA. The physical parameters involve different crystal structures, nanotubes diameter and length, as well as surface roughness. The element contents are the core compositions of TNA. The effect of different parameters could solely or communally modulate diverse cellular responses of the cells adhesion, migration, proliferation and differentiation [3, 4].

Interaction of these parameters may also result in the wettability factors of cellular interaction and biocompatibility [5]. Hence, these parameters need to be optimized before performing a detailed study of the material. This might also help in gaining an understanding of the cellnanostructure interactions and designing novel regenerative biomaterials that could favorably modulate cellular responses to enhance the tissue regeneration [6–8].

The Ti surface readily reacts with oxygen upon contact and results in three titanium oxide crystalline phases such as rutile, brookite and anatase. These phases may also be responsible for the material biological properties [9]. Anatase phase is metastable and exhibit stronger interactions between metal and support, which would be advantageous for medical application [10]. Anatase phase shows better absorption properties of hydroxyl-OH- and phosphate-PO<sup>4</sup> 3+ than rutile titania in simulated body fluid which could favor bonelike apatite component to be deposited [9]. The deposition of bone-like apatite component is crucial in mediating a positive osseointegration, the interaction of implant surface with surrounding bone tissues [11, 12].

Therefore, anatase crystal phase TNA has become a major interest in medical research. A study by Yu et al. [13] reported that anatase TNA could yield an optimal biological response for cell adhesion, spreading, proliferation and differentiation. TNA with 100 nm diameter have been suggested to provide similar characteristic as the natural bone topography comprising nanophase hydroxyapatite (100 nm size regime) in the collagen matrix [14, 15].
