*3.1.2. Nanomatrix therapeutic induction*

The inner volume of TiO2 nanotubes can be also filled with chemicals and biomolecules, such as enzymes or proteins. Subsequently, TNA could be applied into new drug-releasing implants for emerging therapies for localized drug delivery [53, 54]. Whereby, the TNA topology can be coated with inflammation-reducing drugs, such as dexamethasone, by using simple physical adsorption or deposition of the drug by magnetic stimuli-responsive drug delivery system as described in **Figure 2**. This technology may act together radiation therapy and even stem cell transplant for an intensification therapy which also known as consolidation or postremission therapy.

#### *3.1.3. Nano-immunomodulatory agents*

Nanomaterial technology allows the development of new immunomodulatory agents, which are either immunologically active components or immunosuppressive agents. This nanostructured material could effectively surpass vaccination, adjuvants, and other immunomodulatory drug treatments. Besides, this unique surface structure could act together with an immunosuppressive agent to therapeutically prevent damage to immune response toward unsuccessful transplant in allergic or even localized autoimmune reaction. Hence, this technology could improve the clinical outcomes of treatments for a range of infectious and noninfectious diseases [55].

*3.1.4. Nano-antibacterial agents*

*3.1.5. Nano-blood-contacting agents*

reduce the bacteria infection risk from the system.

Bacterial infection of in-dwelling medical devices could be controlled by the technology of TNA nanomatrix surface coated with infection-reducing drugs, such as penicillin and streptomycin (**Figure 3**). Traditional antibiotic treatment is limited in solving the bacterial infection problem. Kulkarni et al. [58] discovered that the use of nanotubes with large diameter (30– 100 nm) might reduce the growth of bacteria, such as *Staphylococcus aureus* and *Staphylococcus* 

Titanium Dioxide Nanotube Arrays for Biomedical Implant Materials and Nanomedicine…

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Adsorption of blood proteins is the immediate primary outcome observed at the implant– liquid interface [55]. TNA able to increase the formation of fibrin network by transforming

**Figure 3. TNA as nano-antibacterial agent**. (A) The TNA could be aligned on any medical device surface (substrate) and may act as antimicrobial chemotherapy agent. (B) The bactericidal antibiotics such as *Penicillin a*nd *Streptomycin* can be coated at TNA cylindrical inner surface. (C) This antibacterial surface will inhibit and avoid bacteria grow, thus may

*epidermidis*, compared with the smaller size of nanotube (20 nm).

**Figure 2. TNA nanomatrix as therapeutics system**. (A) The system composes TNA structures created on a Ti surface, (B) loaded with drug-encapsulated polymer micelles at the top acting as drug-carriers and magnet nanoparticles (MNs) at the bottom of the nanotubes. A magnetic stimulated release of drug-carriers was achieved by activating magnetic nanoparticles loaded at the bottom of the nanotubes. (C) The drug may move from a region of high concentration to one of lower concentration via passive diffusion activity. (D) The stimuli-release concept is based on applying a magnetic field to induce the movement of magnetic particles from the bottom and force the release polymer micelles out from the TNA.
