Inflammatory infiltrate, microvessel density, nitric oxide synthase expression, vascular endothelial growth factor expression, and proliferative activity in peri-implant soft tissues around titanium and zirconium oxide healing caps.

Background: The aim of the present study in humans was to conduct a comparative immunohistochemical evaluation of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS) expression, inflammatory infiltrate, proliferative activity expression, and microvessel density (MVD) in peri-implant soft tissues of titanium and zirconium oxide healing caps. Methods: Five patients, three men and two women (aged 30 to 66 years; mean: 49 years), participated in this study. All patients received dental implants that were 3.8 mm in diameter and 11 mm in length. All implants were left to heal in a non-submerged (single-stage) mode. Healing caps (3.8 mm in diameter and 3.0 mm in height) were inserted in all implants. Half of the implants were supplied with standard, pre-fabricated caps of commercially pure titanium, whereas the other half were provided with test zirconium oxide caps. After a 6-month healing period, a gingival biopsy was performed with a circular scalpel (5.5 mm in diameter) around the healing caps of both groups, without unscrewing or removing the healing caps. The dimensions of the gingival biopsies were 1.7 mm (5.5-3.8 mm) in thickness and 3 mm in height. Results: Statistically significant differences were found in the microvessel density between titanium and zirconium oxide healing caps and group II (P≤0.0001). Statistically significant differences were likewise found in the low and high intensities of NOS1, NOS3, and VEGF (P≤0.0001). In conclusion, the high intensity of NOS1, NOS3, and VEGF were mostly expressed in the titanium group, whereas the low intensity of NOS1, NOS3, and VEGF were mostly expressed in the zirconium oxide group. Conclusions: In our specimens, the inflammatory infiltrate was m ostly present in the titanium specimens. Their extension was much larger than that of the zirconium oxide specimens. Higher values of MVD were observed in the titanium specimens (29.1 versus 15.8). In addition, a higher expression of VEGF intensity was observed in the peri-implant tissues of titanium healing caps, whereas predominantly lower expressions of VEGF intensity were noted around the zirconium oxide healing caps. The Ki-67 expression was higher in the titanium specimens. All these data revealed that the tissues around titanium healing caps underwent a higher rate of inflammation-associated processes, most probably correlated to the higher inflammation processes observed in these tissues. A higher intensity expression of NOS1 and NOS3 was recorded in the tissues around titanium, whereas, on the contrary, a lower intensity of expression was found in the tissues around zirconium oxide specimens. These latter data indicate that the higher expression of these two mediators could be correlated to the higher amount of bacteria present around the titanium samples.