Biomimetic Models Core

仿生模型核心

• 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
• 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

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.

项目摘要 位于特拉华大学（UD）的仿生模型核心B核心B将负责 设计，制造，验证和实施仿生宫颈阴道感染设备以支持所有人 杰森·格莱格恩（Jason Gleghorn）博士的各个项目和整体计划 该模型（V1-V4）将根据相关的需求增长，复杂性的水平越来越高。 在AIM中，将开发一个模块化3D多细胞宫颈或阴道培养系统的项目。 这是由在轨道蚀刻膜上培养的上皮，并带有次上皮式上的室间室室 由衬有成纤维细胞（V1）的细胞胶原凝胶组成。 宫颈粘液将在AIM 2中的附加空气通道内的上皮细胞的顶部表面流动。 具有先进的单个模型，以掺入成纤维细胞嵌入的胶原蛋白凝胶室间定性室， 灌注孔衬有内皮细胞的灌注室（V2）。 除细胞间质外，还包括宫颈阴道过渡区的两个器官模型 灌注室室（V3）。 匹配的供体细胞和重构的细胞外基质（V4）。 模型以及它们的制造方法，并将其转移到项目1、2和 3。项目1侧重于阴道和宫颈微生物群在性传播感染中的作用，并将使用 该模型研究了在存在不同类型的存在的情况下如何改变沙眼感染动力学 Microbiota。 复制，上皮屏障功能和免疫反应，从而将模型的能力构成 模型的激素波动为免疫细胞浸润。 在免疫反应的背景下，淋病感染的微生物群，并将静静地依赖于 模型能够重新分配微生物群 - 宿主相互作用和免疫细胞的作用 核心与项目的需求构想，并使用类似于所使用的测定方法来验证它们的核心 在项目中。