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.

项目总结 总部设在特拉华大学(UD)的仿生模型Core，Core B将负责 设计、制造、验证和实施支持ALL的仿生宫颈阴道感染装置 个别项目和整体方案。核心B将由杰森·格雷霍恩博士执导。的多次迭代 模型(V1-V4)将根据相关客户的需求，随着复杂性的增加而开发 项目。在第一个目标中，将开发一种简化的模块化3D多细胞宫颈或阴道培养系统。 这是由培养在带有上皮下间质隔膜的蚀刻膜上的上皮细胞组成的。 由脱细胞的胶原凝胶和成纤维细胞组成(V1)。所有模型都将接种微生物区系， 宫颈粘液将在缺氧空气通道内的上皮细胞的顶端表面流动。在目标二中， 个别型号将被改进为包含嵌入胶原凝胶间质隔室的成纤维细胞， 和内衬内皮细胞的可灌流血管隔室(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外，还包括宫颈阴道移行区 可灌流的血管隔室(V3)。此外，我们还将演示此系统可以从 匹配的供体细胞和重组的细胞外基质(V4)。最后，同时实现的第四个目标是将这些 模型及其制造方法，并将其转移到项目现场以用于项目1、2和 3.项目1侧重于阴道和宫颈微生物区系在性传播感染中的作用，并将利用 这个模型用来研究沙眼衣原体在不同类型的沙眼衣原体存在下的感染动态是如何改变的 微生物区系。项目2从细菌的角度研究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，因此将利用模型的能力 荷尔蒙波动模型以及免疫细胞渗透模型。项目3考察了 微生物区系对淋病奈瑟菌感染的免疫反应也同样依赖于 模型概括微生物-宿主相互作用和免疫细胞作用的能力。仿生模型 CORE将在考虑到项目需求的情况下开发模型，并使用与使用的分析类似的方法对其进行验证 在项目中。