## 3 General and Local Implications of Titanium Alloys
### Allergic Reactions Associated with Titanium-Based Alloys  
Titanium alloys are popular for their high biocompatibility [93; 94] and tolerance in relation with the human tissue. The large use in the osteosynthesis field with positive outcomes assured the titanium-based alloys a well-deserved first place in surgical reconstructive treatment. Recent studies have focused on reporting several aspects regarding cases that describe developed allergic symptomatology in relation with titanium-based alloys. One explanation could be the fact that the advancement made in materials technology produced titanium-based products with an increased quantity of titanium, sensitizing the human body. [PERSON] et al. [95] published a case report regarding a patient that had developed an allergic reaction--an eczema after an osteosynthesis procedure using a titanium-based material. In this case, the patch test revealed no reactions, and only after an examination of the blood samples, the lymphocytes showed an active response towards TiO\({}_{2}\). Another case report belonging to [PERSON] et al. [96] described the existence of a facial eczema in relation to a titanium dental implant. The patients underwent the lymphocyte transformation tests (LLT)--tests that have been newly recognized to be precise for the testing for metal sensitivity, including titanium [97; 98; 99]. The results showed a reaction towards TiCl\({}_{3}\). The removal of the implants determined the remission of the symptomatology. Cases of titanium allergy are still rarely reported, and it is not recognized as an expected interaction. The most used titanium-based alloys consist of titanium dioxide with a major impact in reconstructive medicine based on their multiple advantages. An increased usage of these alloys determined an inevitable exposure of the human body. Although, while the positive allergic reactions are proven to be against titanium reagents, no patient until recently has developed a positive allergic reaction to only one titanium reagent. Taking into consideration the facts, it is safe to conclude that the incidence is low in comparison to the exposure to other metals, and titanium can be considered a low risk material. Still, changes could potentially arise in the future, as the increased exposure to these types of materials alters the human body response as a consequence. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Reference** & **Titanium-Based Alloys** & **Type of Study** & **Samples** & **Implications and Conclusions** \\ \hline \hline \multirow{8}{*}{[PERSON] et al. [1]} & \multirow{8}{*}{Tt4 AI4V} & \multirow{8}{*}{In vivo} & & - Increased superoxide dismutase (**SOD**) **activity** (redox biomarker) in erythrocytes in the study group compared to the control -**\textgreater{}increased** & **antioxidant defence** \\  & & & - Increase in uric acid (**UA**) concentration both in tissue and blood of the study group compared to the control -**\textgreater{}increased antioxidant defence** \\  & & & - Increased tacrolimus (**TAC**) level in the tissue sample of the target group compared to the control -**\textgreater{}increased oxidant status** \\  & & & Soft tissue sample (periosteum) & - decreased oxidative stress index (**OSI**) value in both blood and tissue samples of the study group in comparison to the control -**\textgreater{}increased** & **oxidant status** \\  & & & - increase of advanced glycation end products (**AGE**) **fluorescence** in the tissue sample (periosteum) of the study group -**\textgreater{}oxidative damage product** & **damage product** \\  & & & - increased advanced oxidation protein products (**AOPP**) concentration in the tissue sample (periosteum) of the study group than in the control one -**\textgreater{}oxidative damage product** & **- elevated enzymes aspartate** \\  & & & & **transaminase/alanine transaminase (**ALT/AST**) levels in the study group** \\ \cline{1-1} [PERSON] et al.