Three-DimensionalIn VitroOral Mucosa Models of Fungal and Bacterial Infections

Abstract

Oral mucosa is the target tissue for many microorganisms involved in periodontitis and other infectious diseases affecting the oral cavity. Three-dimensional (3D) in vitro and ex vivo oral mucosa equivalents have been used for oral disease modeling and investigation of the mechanisms of oral bacterial and fungal infections. This review was conducted to analyze different studies using 3D oral mucosa models for the evaluation of the interactions of different microorganisms with oral mucosa. In this study, based on our inclusion criteria, 43 articles were selected and analyzed. Different types of 3D oral mucosa models of bacterial and fungal infections were discussed in terms of the biological system used, culture conditions, method of infection, and the biological endpoints assessed in each study. The critical analysis revealed some contradictory reports in this field of research in the literature. Challenges in recovering bacteria from oral mucosa models were further discussed, suggesting possible future directions in microbiomics, including the use of oral mucosa-on-a-chip. The potential use of these 3D tissue models for the evaluation of the effects of antiseptic agents on bacteria and oral mucosa was also addressed. This review concluded that there were many aspects that would require optimization and standardization with regard to using oral mucosal models for infection by microorganisms. Using new technologies-such as microfluidics and bioreactors-could help to reproduce some of the physiologically relevant conditions and further simulate the clinical situation.

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

“… 2007 ). However, RHE models do have limitations, such as the lack of supporting cell types, the absence of mucins, non-constant desquamation, and the overgrowth of microbes due to static conditions (Tabatabaei, Moharamzadeh and Tayebi 2020 ). These limitations need to be addressed to gain accurate views of fungal infection.…”

Implant Soft-Tissue Attachment Using 3D Oral Mucosal Models—A Pilot Study

“…It is important to note that the results from the in vitro studies described above were based on monolayer cell culture systems, and can be different when 3D, multi-layered, full-thickness oral mucosal models are used. In previous studies by Chai et al, the interactions between implants and oral soft tissues have been investigated at the interface, using 3D, tissue-engineered human oral mucosa models [ 10 , 11 , 12 , 13 ]. Microscopic imaging has revealed that cells attached to titanium surfaces in both a “pocket” and “non-pocket” manner, depending on the epithelium’s contact angle with the implant surface.…”

“…The 3D model was designed to assess the interaction between dental implants and human oral mucosa in terms of the implant–soft tissue attachment, biological seal, and the interface contour [ 10 ]. Our experiments on the 3D model have shown that the results obtained from multiple-endpoint analysis of the oral mucosa model were more clinically relevant and more informative than monolayer cell culture systems [ 11 , 12 , 13 ].…”

Immunoresponsive Tissue-Engineered Oral Mucosal Equivalents Containing Macrophages

“… 1 OME can be in the form of a reconstituted human epithelium where keratinocytes alone are cultured on a porous membrane or as full-thickness cultures that are composed of a fibroblast-populated connective tissue topped with a stratified squamous oral epithelium. Collectively, these OME have been used in numerous studies to study, among others, oral mucosal microbial infection, 2 , 3 wound healing, 4 , 5 cancer progression, 6 , 7 and oral mucositis, 8 , 9 as well as to examine the response of the oral mucosa to biomaterials and to monitor toxicity, drug delivery, and efficacy. 10–12 …”

“…1 OME can be in the form of a reconstituted human epithelium where keratinocytes alone are cultured on a porous membrane or as full-thickness cultures that are composed of a fibroblast-populated connective tissue topped with a stratified squamous oral epithelium. Collectively, these OME have been used in numerous studies to study, among others, oral mucosal microbial infection, 2,3 wound healing, 4,5 cancer progression, 6,7 and oral mucositis, 8,9 as well as to examine the response of the oral mucosa to biomaterials and to monitor toxicity, drug delivery, and efficacy. [10][11][12] Resident and recruited immune cells are essential for maintenance of oral tissue and are critical in driving host responses to external insults, while dysregulation of the immune response can cause chronic conditions leading to debilitating oral lesions or poor outcomes in the case of oral squamous cell carcinoma.…”