*3.1.5. Nano-blood-contacting agents*

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 reduce the bacteria infection risk from the system.

fibrinogen to fibrin and reduce clotting time also forming dense fibrin network (**Figure 4**). Moreover, TNA elicited low monocyte activation and cytokine secretion. The adsorption of biomaterial and blood able to evaluate by using a micro-BCA assay and X-ray photoelectron spectroscopy (XPS) [56].

molecular detection of biomarkers for disease diagnosis. Biosensors consist of physicochemical transducers (electrochemical, mass, optical, and thermal) and biological analytes as a molecular recognition system. The sensitivity of biosensors depends on the properties of the transducers and the bio-recognition element. Nanostructured transducers with TNA could be used as diagnostic tools with increased sensitivity, specificity, and reliability for medical

Titanium Dioxide Nanotube Arrays for Biomedical Implant Materials and Nanomedicine…

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

477

The nanometric scaled topography of biomedical products plays a decisive role in the surrounding tissue acceptance, cellular stability and cell survival [59–64]. It is important to understand nanomaterials-molecular interactions at different cellular mechanisms in order to predict the safety of nanomaterials application and their long-term effects. The study of molecular signaling pathways could help to explain the cell fate activity when it interacts with this nanomaterial. A study by Arcelli et al. [9] has found that Ti with various surface textures on osteoblast cells is able to regulate the expression of genes that are linked to osteoblast differentiation and bone regeneration such as TIMP1, PTN, and RUNX1 whether directly or indirectly. The indirect mechanism has been found through cell communication (PLCG2 and EPHA7), cellular proliferation, differentiation (MSX1), cycle regulation (RASSF2 and WDR26)

Furthermore, material surface textures interaction may trigger various cellular mechanisms such as tissue remodeling (reorganization or restoration of existing tissues), organization of extracellular matrix and protein development, arrangement and disassembly activities (biogenesis), bone remodeling (bone matrix, reabsorption minerals and bone development), morphogenesis of anatomical structure and macromolecule complex assembly of biological process. Most of material surface textures such as nanorough/nanomaterials interactions are predicted from functional analysis using bioinformatics software such as gene ontology (GO) analysis [64]. However, precise laboratory work needs to be done in accordance with these mechanisms and the knowledge of designing safe nano-biomedical products from molecular genetic aspects. The nanomaterial technology could lead to advances in medical therapies for a variety of diseases, especially cancer. Indeed, nanotechnology may have a great impact in medicine and healthline. However, little is known about the impact of nanotechnology on human health and also on the environment especially in terms of new mechanisms associated with nanotoxicology [4, 65]. Nanomaterial toxicological profile requires the analysis of different endpoints and cellular mechanisms. Numerous studies have indicated that some nanoparticles reveal traces of toxicity in biological systems [66]. This has led to an interest in the area of nanotoxicology, which examines the possible toxicity of nanomaterial products for advanced medical applications. These research issues have underlined the need for toxicogenomic studies which govern the examination of toxicology, genomics, proteomics and metabolomics of human cells interaction with targeted nanomaterial product. The need of molecular biology study on nanomaterial product is important in the development of specific strategies treat-

**4. Molecular cross-talks between TNA and molecular stability**

and cell adhesion (TNC, TNXB, ZFHX1B and TRPM7).

ment especially in nanotherapeutic manipulation.

applications [42].
