Biomimetic Models Core

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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.