3D human periodontal sulcus tissue model to study early fingerprints of oral dysbiosis

About This Grant

Project Summary The oral mucosa, and specifically, the periodontal sulcus, is considered a defense barrier between specialized immune cells and polymicrobial communities. In healthy condition, balanced interactions among the epithelium, microbiota, and immune cells are maintained within the depth of the periodontal sulcus. However, persistent inflammation within the sulcus disrupts the equilibrium, facilitating the growth of pathogenic bacteria and leading to periodontal diseases (gingivitis, periodontitis). At present, the ways in which polymicrobial community influence host physiology and how the innate immune system balance host-pathogen interactions in healthy and disease state are not yet well understood. Moreover, disease trajectory studied by using clinical, animal, or in- vitro models are limited. Specifically, research strategies have failed to mimic key elements of the gingiva, such as anatomical complexity (i.e, sulcus depth at different stages of the disease), polymicrobial native conditions (oxygen and pH levels), and immune components. Thus, there is a compelling need to improve current culture technologies to provide a more sustained in vivo-like environments to investigate host-pathogen interactions in acute and chronic conditions. Therefore, I am proposing a sustained in vitro gingival tissue model, resembling the gingival sulcus anatomy, capable of recreating different periodontal states (healthy, gingivitis, periodontitis), physical properties (i.e., oxygen gradient), and metabolic conditions. Acute and chronic states will be studied with the addition of primary human neutrophils to investigate early dysbiosis clinical fingerprints and monitoring the cytokine profiles in comparison to gingival exudates from patients.