Establishment of an oral infection model resembling the periodontal pocket in a perfusion bioreactor system

Abstract

Periodontal infection involves a complex interplay between oral biofilms, gingival tissues and cells of the immune system in a dynamic microenvironment. A humanized in vitro model that reduces the need for experimental animal models, while recapitulating key biological events in a periodontal pocket, would constitute a technical advancement in the study of periodontal disease. The aim of this study was to use a dynamic perfusion bioreactor in order to develop a gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen sponges. An 11 species subgingival biofilm was used to challenge the generated tissue in the bioreactor for a period of 24 h. The histological and scanning electron microscopy analysis displayed an epithelial-like layer on the surface of the collagen sponge, supported by the underlying ingrowth of gingival fibroblasts, while monocytic cells were also found within the sponge mass. Bacterial quantification of the biofilm showed that in the presence of the organotypic tissue, the growth of selected biofilm species, especially Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine secretion showed that interleukin (IL)-1 β, IL-2, IL-4, and tumor necrosis factor (TNF)-α levels in cell culture supernatants were significantly up-regulated in presence of the biofilm, indicating a positive inflammatory response of the organotypic tissue to the biofilm challenge. In conclusion, this novel host-biofilm interaction organotypic model might resemble the periodontal pocket and have an important impact on the study of periodontal infections, by minimizing the need for the use of experimental animal models.

Pressure Cycling Technology Assisted Mass Spectrometric Quantification of Gingival Tissue Reveals Proteome Dynamics during the Initiation and Progression of Inflammatory Periodontal Disease

“…Comparisons made between consecutive time points showed that the number of upregulated proteins was increased during the progression of the disease, an observation that is in agreement with the current literature on transcriptomics changes in the gingival tissues during the course of experimental periodontitis . Another commonly used approach for investigating differences between the studied groups is to place the differentially regulated proteins in the context of pathways or processes and place an emphasis on the proteins in the top enriched categories . Many of the top enriched GO terms in the protein localization category were “extracellular” or “secretory related.” This may not be surprising since oral biofilms are known to stimulate the secretion of several inflammatory molecules .…”

Options and Limitations in Clinical Investigation of Bacterial Biofilms

“…Biofilms account for 80% of chronic microbial human infections, leading to increased rates of hospitalization, elevated health care costs, and increased mortality and morbidity rates (6). Upper and lower respiratory tract diseases, native valve endocarditis, chronic otitis media, eye infections, chronic wounds, diabetic foot ulcers, urinary tract infections (UTIs), and periodontitis are all biofilm-associated diseases (7)(8)(9)(10)(11)(12). Biofilms can also develop on abiotic surfaces, including medical devices such as orthopedic prostheses, artificial cardiac valves, coronary stents, intravascular and urinary catheters, neurosurgical, cochlear, and breast implants, dentures, and ventricularassist and ocular devices (13).…”

Commensal and pathogenic biofilms differently modulate peri‐implant oral mucosa in an organotypic model

“…The in vivo situation is much better reflected in three dimensional (3D) organotypic models (Antoni, Burckel, Josset, & Noel, ). The co‐culture of organotypic oral mucosa models with planktonic bacteria, monospecies biofilms, or even multispecies biofilms facilitated in vitro studies, which explored the impact of host–microbe interactions (T. Ahlstrand et al, ; Andrian, Grenier, & Rouabhia, ; Bao, Papadimitropoulos, Akgul, Belibasakis, & Bostanci, ; Buskermolen et al, ; Diaz et al, ; Gursoy, Pollanen, Kononen, & Uitto, ; Pinnock, Murdoch, Moharamzadeh, Whawell, & Douglas, ). In order to study the soft‐tissue‐implant interface, Chai et al .…”