Recently, Kim et al. reported an in vitro experiment regarding the expression of mucin genes in human airway epithelial cells. The authors confirmed that TiO₂-NP initiated the TLR4-dependent pathway, leading to the MUC5B overproduction, which relates to the inflammatory response in human airway. In Suarez-Lopez del Amo et al. experiment, the TiO₂ particles derived following implantation were collected and co-cultured with the oral epithelial cells (NOK-SI). Two markers DDR and BRCA1 were used to detect DNA damage repair. The authors suggested that compared to DDR, BRCA1 is an optimal marker for detecting DNA damage induced by Ti particles.

Ti implants are always inserted into diverse complex body environments which contain various inorganic and organic molecules, as well as living cells. Therefore, besides the behavior of Ti particles in animal body and cell culture, the influence of serum proteins or other biomolecules on titanium implant has been studied under different experimental conditions. Jackson et al. studied the absorption behaviors of bovine fibrinogen and bovine serum albumin (BSA) at the commercially pure titanium surface. The releasing of titanium particles into surrounding tissue by protein adsorption and subsequent desorption of formed metal-protein complexes can cause varieties of tissue reactions. It has been also demonstrated that some conditions such as inflammation or formation of microbial biofilm can lead to a locally acidified environment, and this environment can be potentially harmful to titanium implant. Yu et al. gave attention to lipopolysaccharide (LPS) due to its crucial role as a mediator in peri-implant inflammation. The study demonstrated that LPS significantly inhibited Ti release under the low acidic conditions (pH = 2) but promoted Ti release at the mildly acidic and neutral pH levels, which supposed to be encountered in the peri-implant environment.

To approach the mechanism of body reaction to TiO₂-NP, many studies reported inflammatory effects due to TiO₂-NP exposure, including the presence of pro-inflammatory mediators, macrophage inflammatory proteins, and other inflammatory molecules.