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.

项目摘要 位于特拉华州大学（UD）的仿生模型核心（Core 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 个别项目和整体方案。核心B将由Jason Gleghorn博士指导。的多次迭代 该模型（V1-V4）的开发将根据相关的需求， 项目在目标一中，将开发简化的模块化3D多细胞宫颈或阴道培养系统。 这包括在径迹蚀刻膜上培养的上皮细胞和上皮下间质室 由衬有成纤维细胞的脱细胞胶原凝胶组成（V1）。所有模型都将接种微生物群， 并且宫颈粘液将在缺氧空气通道内的上皮细胞的顶端表面上流动。在目标二中， 将推进个体模型以结合成纤维细胞包埋的胶原凝胶间质隔室， 和内衬有内皮细胞的可灌注血管隔室（V2）。第三个目标将包括： 这两种器官模型除了细胞间质外还包括宫颈阴道过渡区， 可灌注血管室（V3）。此外，我们将证明该系统可以从 匹配的供体细胞和重建的细胞外基质（V4）。最后，第四个目标是把这些 模型，沿着其制造方法，并将其转移到项目现场，用于项目1、2和 3.项目1的重点是阴道和宫颈微生物群在性传播感染中的作用， 该模型研究了C.沙眼感染动力学在不同类型的 微生物群项目2研究C.细菌性沙眼感染 复制，上皮屏障功能和免疫反应，因此将利用模型的能力， 模拟荷尔蒙波动和免疫细胞浸润。项目3审查了 微生物群对N.淋病感染的背景下的免疫反应，并将同样依赖于 模型再现微生物-宿主相互作用的能力和免疫细胞的作用。仿生模型 核心将开发模型与项目的需要铭记和验证他们使用类似的分析使用 在项目中。