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Objectives The purpose of this experimental in vivo investigation was to evaluate the influence of modifying the implant surface by adding a monolayer of multi‐phosphonate molecules on the de novo bone formation and osseointegration. Material and Methods The study was designed as an animal preclinical trial with intra‐animal control and two healing periods, 2 and 8 weeks, to compare implants with an identical macro‐design but with two different surfaces. Eight female Beagle dogs participated in the study. Control implants had a moderately rough surface combining sandblasting and acid etching; test implants had an additional monophosphonate layer covalently bonded to titanium. Histologic and radiographic (micro‐CT) outcome variables were evaluated. Results The first bone‐to‐implant contact (fBIC) was located more coronally for the test implants at the first (0.065 mm (95% CI = −0.82, 0.60)) and second healing milestones (0.17 mm (95% CI = −0.9, 0.55)). Most coronal BIC of the test implants displayed a higher percentage of osseointegration, +6.33% and +13.38% after 2 and 8 weeks, respectively; however, the differences were not statistically significant. The micro‐CT examination did not show any BIC difference. Conclusions The monophosphonate layer coating demonstrated clinical, histological, and radiographic results similar to the control surface.

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