## 4 Discussion
However, several studies have reported findings of other elements in the implant surface such as nitrogen (N), F, P, chloride (Cl), and Na together with some inorganic impurities such as Al, zinc (Zn), Si, and Mg, among others [17; 19]. These inorganic chemical compositions are suggested to be the products of a corrosion process [20]. The detachment of ions and metal particles into the peri-implant tissue may result in a biological response that can be devastating and enhance the high risk of severe complications. Some metals associated with alloys used in dental implants, such as copper (Cu), Al, Ag, vanadium (V) and Mn (Manganese), are associated with high cytotoxicity and reduced cell viability. [PERSON] et al. [21] studied the cytocompatibility of pure metals and experimental binary Ti alloys for implant materials and suggested that the ranking of pure metal cytotoxicity from most potent to least potent was as follows: Cu > Al > Ag (Silver) > V > Mn > Cr (Chromium) > Zr > Nb (Niobium) > Mo (Molybdenum) > commercial pure Ti (CP-Ti). [PERSON] et al. [22] demonstrated a possible effect of Al nanoparticles (AlNPs) in the immune system, in that AlNP exposure caused cytokine-level changes in the spleen, thymus, and serum, besides causing damage to immune organs and dysfunction of immune cells. To date, the systemic toxicity of AlNPs derived from dental implants has not been reported. Locally, AlNPs, with their triggering of immune cell dysfunction, could be the suggested trigger of abnormal immune-related cytokine behavior, which led to an inflammatory reaction of the Schneiderian membrane in the present context. The EDS analysis is a semi-quantitative technique dominantly used to analyze implant surface characteristics in different scenarios [23]. Although it has been proven to be a reliable and a practical method, there is no consensus on the chemical compositions of dental implants. Ti concentration in CP-Ti implants is reported to range approximately from 22.5% [18] to 100% [17], while also finding the existence of some impure contents such as Al, Fe, Si and Na [24]. In this study, EDS compositional maps of the failed implants provide evidence of C and O enrichment in the surrounding bone. In addition, the Ca level was high while the P level was low or undetectable in all three cases. The Ca/P ratio may vary depending on the bone type, location, and loading function; and the determination of this ratio can reveal the bone density change. Theoretically, the fraction of Ca in hydroxyapatite is 40.3% and that in P is 18.4%. [PERSON] et al. [25] reported that the Ca/P ratio in monkey mandible was 1.56 to 1.68. In the infected bone region of the current cases, the Ca/P ratio was almost negligible. This finding confirmed the heterogeneous morpho-chemistry of the affected bone. The Ti components of the implant are within the normal range; however, minor components including F, Na, and Si and traces of other elements such as Au, Al,and Mg revealed the contamination of the implant, which may be the reason for the sinus membrane irritation and inflammation. The presence of Si, Na, Al, and Mg come from the manufacturer and surface finishing process in the Ti implant preparation [26]. The Si contamination can also originate from the ion dissolution from the glass storage vials [27]. Na and F can come from the body fluids or the environment during handling installation. The Au can be the dissolved product from the intraoral gold prosthesis during function or galvanic current activity. Previous studies suggested that some micro- and submicro-sized metal particles trapped by the mucus tissue of the upper respiratory tract can travel through the mechanical barrier of the mucosal tissue and penetrate the tissue, which may initiate various pathological states. A study by [PERSON] et al. [28] found metal particles such as Ti, Zn, Fe, and Ba from the cytological mucus and hypertrophic tissue samples from a patient diagnosed with chronic hypertrophic rhinosinusitis characterized by scanning electron microscopy and Raman microspectroscopy.