Biomimetic Models Core

仿生模型核心

基本信息

批准号：
10395580
负责人：
Jason Paul Gleghorn
金额：
$ 25.41万
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/10395580
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 Devices Endocrine Endothelial Cells Ensure Environment Epithelial Epithelial Cells Equipment Extracellular Matrix Family Fibroblasts Gel Goals Growth Hormonal Hormones Human Human Microbiome Hydrogels Immune Immune response Immunity In Vitro Individual Infection Infection prevention Infiltration Instruction Lactic acid Lactobacillus Learning Liquid substance Membrane Menstrual cycle Methods Mind Modeling Mucous body substance Neisseria gonorrhoeae Organ Organ Model Pathogenicity Perfusion Phenotype Physiological Physiology Pregnancy Production Proteins Recording of previous events Role Sexually Transmitted Diseases Site Standard Model Structure Surface System Techniques Technology Transfer Tissues Training Tumor-infiltrating immune cells Universities Vagina Vascular Endothelium base cell type cervicovaginal design experience host microbiota imaging capabilities 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.

项目概要位于特拉华大学 (UD) 的仿生模型核心核心 B 将负责设计、制造、验证和实施仿生宫颈阴道感染装置，以支持所有各个项目和整体计划将由 Jason Gleghorn 博士指导。模型（V1-V4）将根据相关的需求以越来越复杂的程度进行开发项目的目标一是开发一种简化的模块化 3D 多细胞宫颈或阴道培养系统。它由在径迹蚀刻膜上培养的上皮细胞和上皮下间质室组成由衬有成纤维细胞的无细胞胶原蛋白凝胶 (V1) 组成。所有模型都将接种微生物群，宫颈粘液将在缺氧空气通道内的上皮细胞顶端表面流动。个别模型将被改进以纳入成纤维细胞嵌入的胶原凝胶间质室，第三个目标将包括内皮细胞（V2）的可灌注血管室。这两个器官模型除了细胞间质和细胞间质外还包括子宫颈阴道过渡区此外，我们将证明该系统可以由可灌注血管室（V3）创建。最后，同时进行的第四个目标是获取这些匹配的供体细胞和重建的细胞外基质。模型及其制造方法，并将它们转移到项目现场以供项目 1、2 和 3. 项目 1 重点关注阴道和宫颈微生物群在性传播感染中的作用，并将使用该模型用于研究沙眼衣原体感染动态在不同类型的存在下如何改变微生物群。项目 2 研究细菌背景下沙眼衣原体感染的内分泌控制。复制、上皮屏障功能和免疫反应，因此将利用该模型的能力模型荷尔蒙波动以及免疫细胞浸润项目 3 检查了影响。在免疫反应的背景下，微生物群对淋病奈瑟菌感染的影响，同样依赖于模型重现微生物群与宿主相互作用和免疫细胞作用的能力。 Core 将根据项目的需求开发模型，并使用与所使用的类似的分析方法对其进行验证在项目中。