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Biomimetic Models Core

仿生模型核心

基本信息

批准号：
10596509
负责人：
Jason Paul Gleghorn
金额：
$ 52.19万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-20 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10596509
关键词：
3-Dimensional Adopted Air Animal Model Apical Bacteria Bacterial Infections Biological Assay Biological Models Biomimetics Bioreactors Blood Vessels Caring Cell Compartmentation Cells Cervical Cervix Mucus Cervix Uteri Chlamydia trachomatis Clinical Research Collagen Communities Complex Data Delaware Democracy Devices Endocrine Endothelial Cells Environment Epithelial Cells Epithelium Equipment Extracellular Matrix Family Fibroblasts Gel Goals Growth Hormonal Hormones Human Hydrogels Immune Immune response Immunity In Vitro Individual Infection Infection Control Infection prevention Instruction Lactic acid Lactobacillus Learning Liquid substance Membrane Menstrual cycle Methods Modeling Mucous body substance Neisseria gonorrhoeae Organ Organ Model Pathogenicity Perfusion Phenotype Physiological Physiology Pregnancy Production Proteins Recording of previous events Role Rotation Sexually Transmitted Diseases Site Standard Model Structure Surface System Techniques Technology Transfer Tissues Training Universities Vagina Vascular Endothelium cell type cervicovaginal design experience fabrication host microbiota imaging capabilities immune cell infiltrate in vitro Model in vivo interstitial interstitial cell microbial microbiome microbiota microphysiology system pathogen pathogenic bacteria programs reconstitution response vaginal microbiome web site

项目摘要

PROJECT SUMMARY The Biomimetic Models Core, Core B, based at the University of Delaware (UD), will be responsible for designing, fabricating, validating, and implementing biomimetic cervicovaginal infection devices in support of all individual projects and the overall program. Core B will be directed by Dr. Jason Gleghorn. Multiple iterations of the model (V1-V4) will be developed with increasing levels of complexity based on the needs of the associated projects. In aim one, a simplified modular 3D multicellular cervical or vaginal culture system will be developed. This consists of an epithelium cultured on a track-etched membrane with a subepithelial interstitial compartment consisting of an acellular collagen gel lined with fibroblasts (V1). All models will be inoculated with microbiota, and cervical mucus will flow on the apical surface of epithelial cells within an anoxic air channel. In aim two, the individual models will be advanced to incorporate a fibroblast embedded collagen gel interstitial compartment, and a perfusable vascular compartment lined with endothelial cells (V2). The third aim will include integration of the two organ models to include a cervicovaginal transition zone in addition to the cellular interstitial and perfusable vascular compartment (V3). Additionally, we will demonstrate that this system can be created from matched donor cells and reconstituted extracellular matrix (V4). Finally a concurrent fourth aim is to take these models, along with their methods of fabrication, and transfer them to project sites for use in Projects 1, 2, and 3. Project 1 focuses on the role of vaginal and cervical microbiota in sexually transmitted infections and will use this model to study how C. trachomatis infection dynamics are altered in the presence of different types of microbiota. Project 2 investigates endocrine control of C. trachomatis infection in the context of bacterial replication, epithelial barrier function, and immune response, and will thus make use of the model’s ability to model hormonal fluctuations as well as immune cell infiltration. Project 3 examines the influence of the microbiota on N. gonorrhoeae infection in the context of the immune response and will similarly rely on the models’ ability to recapitulate microbiota-host interactions and the role of immune cells. The Biomimetic Models Core will develop models with the projects’ needs in mind and validate them using assays similar to those used in the projects.

项目总结