Three-dimensional humanized gingival tissue model to study oral microbiome

Abstract The oral cavity contains different microenvironments, as the non-shedding surface of the teeth and the epithelial mucosa, where oral barriers and microbial communities coexist. The interactions and balances between these two communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium is the first necessary step towards chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental models able to mimic the structural, physical, and metabolic conditions present in the oral gingival tissue to support the long-term investigation of host-pathogens unbalances. Herein, we report a 3D anatomical gingival in vitro model based on human primary culture that recapitulates the native tissue organization, and a native oxygen gradient within the gingival pocket to support human microbiome persistence with a physiologically relevant level of microbial diversity as well as native spatial organization. The modulation of inflammatory markers in the presence of oral microbiome suggested the humanized functional response of this model. The model will be used in future studies to investigate host-pathogen unbalances in gingivitis and periodontal disease.