*3.1.1. Nanodrug delivery agents*

Notably, the proposed TNA structure has adaptive features which are required to successfully improve cell interaction with the implant materials. The continuous and vertically aligned TNA topography demonstrates extremely larger surface area than the flat titanium surface and has been assumed to overcome current clinical implants limitations [31]. Moreover, this improved

tube layer to the titanium metal which eventually rectifies the problems of existing ceramic coatings arising from weak interfacial bonding [28]. Besides that, TNA topography may provide similar characteristic as a natural bone topography (pore size/diameter ~ 60–100 nm) that

Furthermore, the unique structure of TNA exhibit surface area that is three times higher than that of flat titanium, creating additional spaces for cell interaction particularly at the cell extracellular matrix level; this structure may also address the limitations of existing clinical implants [14, 21, 32, 33]. Moreover, the improved bioactive layer of the oxide nanotube structures on Ti allows the nanotube layer to adhere to the titanium metal (metastable), leading to stronger interfacial bonding that that of existing ceramic coatings [34]. These nanostructure properties can increase the surface energy and improve interactions with various proteins (such as vitronectin and fibronectin), resulting in enhanced specific cell adhesion and osseointegration [13, 35–38]. Yu et al. [13] reported that anatase TNA elicits optimal biological responses for cell adhesion, spreading, proliferation, and differentiation. Furthermore, the surfaces of these nanostructures can effectively reduce inflammatory responses compared with surfaces of conventional implants [39–41]. Therefore, the proposed TNA structure possesses adaptive features that can successfully improve cell interaction with the implant mate-

An orthopedic implant is a medical device built from metallic alloys such as Ti which is used to replace a missing joint or bone or to support a damaged bone. It may consist of a single type or comprise modular parts of biomaterial. For example, bone plates and bone screws used in spinal fusion surgery and fixation of fractured bone part. Meanwhile, the hip and knee replacements are medically termed as artificial joints or prostheses used to treat various type of arthritis affecting these joints, which are common health complaints in elderly patients. Besides, the bone implants are also used to treat the bone damaged from accident or cancer or

Dental implant is an artificial tooth root made of Ti used to place into the jaw and hold a dental prosthesis as replacement for tooth or bridge. This technique was invented in 1952 by a Swedish orthopedic surgeon named Per-Ingvar Brånemark [45]. The implant is considered the standard in replacement of missing teeth due to periodontal diseases, injuries, or some other reasons [46]. Dental implants are divided into three types, namely, the osseointegrated, miniimplant for orthodontic anchorage, and zygomatic [47]. Besides, another important implant used in dental application is the titanium mesh membrane. This barrier implant membrane surface provides great mechanical properties for Guided Bone Regeneration (GBR) treatment

nanotubes on Ti provides good adherence of the nano-

bioactive layer of inward growth TiO2

472 Titanium Dioxide - Material for a Sustainable Environment

might improve the interference of bone cells response [15].

rials and may potentially enhance osseointegration [42–44].

**2.1. Examples of biomedical implants**

musculoskeletal diseases [30].

to assist the new bone formation [48].

New nanoengineering approaches allow target drug delivery, improve drug solubility, increase therapeutic index, extend drug half-life, and decrease drug immunogenicity. Nanotherapeutics enables the delivery of drugs to specific cells by using nanostructured materials [51]. This property overcomes the limitations of systemic drug administration and may potentially revolutionize treatment of numerous diseases [52].
