Decoding host-microbial dynamics in peri-implantitis: Ecosystem-specific experimental models

Peri-implantitis is an inflammatory disease arising within a unique host-microbial-biomaterial ecosystem. Unlike periodontitis, peri-implant tissues lack a periodontal ligament and epithelial junction integrity and interface with metal oxides on titanium surfaces. The inflammatory changes in peri-implant disease not only affect the host but also extend to the implant surfaces, which undergo corrosion and particle release. These specific ecological features must be accurately captured in preclinical experimental models to provide mechanistic insight and enable translational success.

This review evaluates preclinical and microengineered models of peri-implantitis, focusing on how well they recapitulate the peri-implant mucosal barrier, the biomaterial interface, and systemic modifiers. We propose minimum criteria for "true" peri-implantitis models and outline ecosystem-specific platforms for translational research.

A literature search for this narrative review was conducted in PubMed, prioritizing in vivo peri-implantitis models and their use in assessing systemic comorbidities (e.g., diabetes) and local risk factors on peri-implant disease. Furthermore, emerging implant-specific organ-on-a-chip systems for 3D peri-implant mucosa are reviewed.

Ligature- and infection-based rodent and large-animal models have elucidated key bacterial-driven inflammatory pathways around dental implants, but careful consideration is needed to ensure long-term chronicity and to account for titanium degradation as a costimulatory pathogenic factor. Comorbidity-integrated models demonstrate that diabetes, vascular disease, and antiresorptive therapy amplify peri-implant bone loss and can precipitate MRONJ-like lesions. Organ-on-a-chip peri-implant mucosa platforms now enable controlled bacterial and titanium exposure, biomechanical strain, and human-relevant barrier readouts, aligned with reduction principles and prioritizing Human-Centered models.

Ecosystem-specific models that incorporate microrough titanium, inflammatory biomaterial corrosion, barrier biology, and systemic risk factors are essential to advance the study of peri-implantitis. Such models provide a strong foundation for implant-specific investigations that move peri-implantitis management beyond biofilm-centric debridement into the management of host-microbial-biomaterial equilibrium.