Biomimetic Models Core

仿生模型核心

• 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
• 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

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 个别项目和总体计划。 Core B 将由 Jason Gleghorn 博士执导。多次迭代 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。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 (V1) 的无细胞胶原蛋白凝胶组成。所有模型都将接种微生物群， 宫颈粘液会在缺氧空气通道内的上皮细胞顶端表面流动。在目标二中， 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， 和内衬内皮细胞的可灌注血管室（V2）。第三个目标将包括整合 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 可灌注血管室（V3）。此外，我们将演示该系统可以通过以下方式创建： 匹配的供体细胞和重建的细胞外基质（V4）。最后，同时存在的第四个目标是实现这些 模型及其制造方法，并将它们转移到项目现场以用于项目 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 模拟荷尔蒙波动以及免疫细胞浸润。项目 3 检验了 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。仿生模型 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。