3D Oral Mucosal Models for Studying Host-Pathogen Interactions in Periodontal Disease

The host immune response to the oral biofilm plays a central role in the aetiology of periodontitis. Our understanding of hostpathogen interactions has historically been reliant on monolayer culture systems stimulated by microorganisms. However, 2D culture systems possess major shortcomings as these do not adequately mimic the complexities of the native tissue and therefore fail to provide meaningful information on the pathogenesis of periodontal disease. To mimic the in vivo condition, various types of 3D oral mucosal equivalents (OME) have been employed, including reconstituted models and 3D organotypic culture models. The rationale for OME is to serve as a relevant in vitro tool to examine the interactions of human epithelial cells with bacterial biofilms, to understand the process of epithelial layer damage, molecular mechanisms underpinning the development of periodontitis and models for testing novel therapeutics. Furthermore, to gain a deeper understanding of periodontal dysbiosis, it is important to appreciate the molecular mechanisms underlying host epithelial cell production of cytokines and chemokines in response to bacterial stimulation; and signalling pathways which underpin host-pathogen interactions such as mitogen-activated protein kinases (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFkB). Thus, the aim of this narrative review is to summarise the evidence regarding the application of 3D oral mucosal models in host-pathogen infection studies relating to periodontal disease, review the molecular mechanisms underlying host response and provide recommendations for future studies in this field.