A Standardized Rat Model to Study Percutaneous/permucosal Osseointegrated Implants Peri-implantitis

Abstract Background: Percutaneous/permucosal osseointegrated implants(POI) are increasingly utilized in clinical practices. However, POI peri-implantitis because of bacterial colonization remains an unsolved problem. With the high incidence rate, distinctive implant characteristic and unique infection pattern, POI peri-implantitis requires a specially designed implant animal model for the researches on the pathogenesis and treatments. Although POI peri-implantitis animal models in forelimb or oral cavity have been utilized in several studies, their high variability in terms of implant site selection, implant design and surgical procedures, etc. , have led to unnecessary tissue damage and less effectivity. Herein, a quantitative-analysis-based standardized rat model for POI related research was proposed. Methods: The hard and soft tissue anatomical structures in region anterior to maxillary molar of rat were systematically evaluated by micro-computed tomography (micro-CT) and vascular perfusion to obtain the best surgical site. We then managed to standardize the model by controlling the age, weight, gender of rats and designing implant based on the quantitative-analysis of available volume of bone and soft tissue. Besides,customized instruments andstep-by-step surgical procedures were developed to avoid damage important structures and reduce the variations.Finally, comprehensive assessments including the expression of biomarkers, micro-CT, and histological images were conducted to verify the model. Results: After dissecting the anatomic structures of rat maxilla, we found that placing the implant anterior to the first molar could reduce experimental period and improve animal welfare. We standardized the model by including Sprague-Dawley male rats weighing 450–500g and aged 12–13 weeks. The customized implant size, shape, and a series of matched surgical instruments were appropriately designed. A clear,step by step, surgical process was established. The aforementioned designs ensured the success rate, stability, and replicability of the model.Each validation method confirmed the successful construction of the model. Conclusions: This study proposed a quantitative-analysis-based standardized POI peri-implantitis rat model with improved animal welfare and reliable procedures. This model could provide efficient in vivo insights to study the pathogenesis and treatmentsof POI peri-implantitis and preliminary screening data for further large animal and clinical trials.