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In vitro 3D human gingival tissue model to study oral microbiome

用于研究口腔微生物组的体外 3D 人类牙龈组织模型

基本信息

批准号：
10603407
负责人：
Chiara Ghezzi
金额：
$ 15.41万
依托单位：
UNIVERSITY OF MASSACHUSETTS LOWELL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10603407
关键词：
3-Dimensional Anatomy Animal Experiments Artificial Saliva Bone Resorption Buffers Chronic Clinical Communities Dental Materials Dentifrices Direct Costs Disease Disease model Ecosystem Environment Epithelium Equilibrium Facilities and Administrative Costs Gingiva Gingivitis Health Homeostasis Host Defense Human Immunology In Vitro Inflammation Inflammatory Irritants Liquid substance Maintenance Metabolic Modeling Mucous Membrane Oral Oral cavity Outcome Oxygen Pathogenesis Patients Periodontitis Physiological Production Saliva Sampling Scientist Symptoms System Testing Time Tissue Engineering Tissue Model Tissues Tooth Loss antimicrobial chemokine clinically relevant community organizations consumer product cost estimate cytokine design dysbiosis effective therapy improved in vitro Model microbial microbial community nutrition oral care oral condition oral microbial community oral microbiome oral pathogen oral tissue pathogen response shear stress tool tooth surface

项目摘要

PROJECT SUMMARY The oral cavity contains different microenvironments, i.e. 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. Current experimental animal and in vitro models do not fully resemble the human condition. To improve clinical outcomes and design effective treatments, new humanized experimental tools are needed to further elucidate these initial host-pathogens unbalances. Previously developed in vitro systems have been used to test irritant responses of new dental materials, dentifrices, and oral care consumer products, but are unable to maintain the complexity of the oral pathogen community organization, due to the lack of the native oxygen and metabolic conditions. In addition, host saliva contributes to the maintenance of the overall oral system stability by buffering the oral environment, providing nutrition to the different communities and delivering antimicrobial features. Therefore, the recapitulation of physiological oral conditions, including oxygen gradients, physiological shear stress, and buffering from saliva will enhance the functions of a humanized sustained gingival tissue model to study initial host-pathogen interactions in vitro. We are proposing to design a physiological culture system based on artificial saliva in order to support long-term culture after inoculation with oral microbiota derived from healthy patients. We will replicate the stability of the ecosystem and evaluate the contribution of host saliva to buffer and provide nutrition to the oral community, as well as physiological shear stress that contributes to the maturation and maintenance of a healthy epithelium. The 3D anatomical gingival tissue model has been shown to modulate the production of a range of cytokines and chemokines in response to interactions with inoculated plaque samples from healthy patients. To assess the clinical relevance of this response, we will study the production of selected cytokines under different conditions; response to the addition of plaque derived from healthy and diseased (gingivitis) patients in comparison to crevicular fluid extracted from the same pool of patients. The efforts will elucidate the initial interactions and balances between these two communities that are responsible for the oral tissue homeostasis or dysbiosis, that ultimately dictates healthy or diseased tissue states. The interdisciplinary team involved in the project has established collaborative activities and includes material scientists, tissue engineers, microbiologists, and periodontists. They are experts in host-material interactions, advanced in vitro tissue and culture models, microbial pathogenesis, host defense, periodontal immunology, and periodontal inflammation.

项目总结