Peri-implant disease pathogenesis animal models: Consensus report of Workgroup 1 of the IADR Implantology Research Group Best Evidence Consensus Symposium on Peri-Implant Disease and Its Treatment.

Background The pathogenesis and etiology of peri-implantitis demand a deeper understanding to lead to successful treatment modalities. Animal models of peri-implantitis pathogenesis offer unique insights but their translational impact requires consideration of implant biomaterials science. This systematic review, sanctioned by the International Association for Dental Research (IADR) Implantology Research Group, aimed to systematically review animal models in peri-implant disease research. Experts deliberated on merits, limitations, and optimization of various models to guide researchers in selecting suitable platforms for investigations.Methods A pre-registered review (ID: CRD42023399976) was performed guided by the PICO question: Population (P): Laboratory animals with dental implants or surrogate biomaterials placed in the oral cavity; Intervention (I): Induction of peri-implant inflammation; Control (C): Animals without induced inflammation or those subjected to a placebo treatment only; Outcome (O): Parameters including bone loss, histopathology of peri-implant tissues, tissue inflammatory response, and microbiological outcomes.Results Searches identified 158 articles, with 96 meeting inclusion criteria following a 2-step systematic review (inter-reviewer agreement: kappa = 0.72; 0.68, respectively for each phase). Most studies were on large animal models, mainly dogs (n = 66); the majority employed ligature-induced peri-implant defect models. These models often reported delayed implant placement after teeth extraction followed by active breakdown via ligatures of various types, and a chronicity progression period without the ligatures to assimilate chronic inflammatory lesions. Primate studies (n = 6) were published from the late 1990s to early 2000s. Murine models in mice (n = 16) focused on disease establishment and biomolecular aspects, while rat models (n = 6) addressed diabetes, xerostomia, and inflammation suppression. Murine models invariably required custom implant devices due to volume limitations, which often did not have implant surface modifications limiting their translational potential. Mini-pig models (n = 2) delved into microbiological shifts and the impact of soft tissue management on peri-implant infection.Conclusion Comprehensive overview of animal models in peri-implant disease research offered insights into their strengths, challenges, and findings. The ongoing shift toward non-animal alternatives and future horizons in peri-implantitis research is highlighted.Plain Language Summary This commissioned systematic review provides a comprehensive overview of animal models in peri-implant disease research, offering insights into their strengths, challenges, and findings. Further, this article summarizes the consensus proceedings of the IADR IRG Peri-Implantitis Best Evidence Consensus and provides guidance for future use of animals in peri-implantitis research.