Advances in modeling periodontal host-microbe interactions: insights from organotypic and organ-on-chip systems

Periodontal disease, a chronic inflammatory condition affecting the supporting structures of teeth, is driven by an imbalanced interaction between the periodontal microbiota and the host inflammatory response. Beyond its local impact, periodontal disease is associated with systemic conditions such as diabetes mellitus, cardiovascular disease, and inflammatory bowel disease, emphasizing the importance of understanding its mechanisms. Traditional pre-clinical models, such as monolayer cultures and animal studies, have provided foundational insights but are limited by their physiological relevance and ethical concerns. Recent advancements in tissue engineering and microfluidic technologies have led to the development of three-dimensional (3D) organotypic culture models and organ-on-chip systems that more closely mimic native tissue microenvironments. This review provides an overview of the evolution of methods to study periodontal host-microbe interactions, from simple 2D monolayer cultures to complex 3D organotypic and microfluidic organ-on-chip (OoC) models. We discuss various fabrication strategies, host-microbe co-culture techniques, and methods for evaluating outcomes in these advanced models. Additionally, we highlight insights gained from gut-on-chip platforms and their potential applications in periodontal research and understanding oral-systemic links of periodontal disease. Through a comprehensive overview of current advancements and future directions, this review provides insights on the transformative potential of OoC technology in periodontal research, offering new avenues for studying disease mechanisms and developing therapeutic strategies.