Abstract (Overall) The University of Rochester (UR) and Duke University will establish a Translational Center for Barrier MPS (TRaCe-bMPS) to create drug development tools (DDTs) focused on the role of barrier functions in disease, injury, and infection. The overall goal of the Center is to submit full qualification packages to the FDA for five DDTs relevant to the treatment of: 1) central nervous system (CNS) disorders, 2) fibrosis, 3) musculoskeletal autoimmune disease, 4) sepsis, and 5) osteomyelitis. For each DDT we have assembled an experienced and multidisciplinary team to establish reproducibility of biomarker assessments for clinically important contexts of use (CoU). Each DDT will be based on an existing, validated MPS model and leverage the modular µSiM MPS platform which provides design flexibility along with translationally relevant permeability and imaging at the interface between tissue compartments. The TRaCe-bMPS will comprise: 1) a Qualification Program (QP), 2) a Resource Core (RC), and 3) an Administrative Core (AC). These units will work together to achieve the Center’s five-year mission while establishing sustainability through commercialization, collaboration, and resource sharing. The QP will develop DDTs and standard operating procedures (SOPs) and achieve answer-in-sample-out functionality through live cell imaging and integrated sensor technologies. Reproducibility for each DDT will be established in at least two laboratories. Qualification plans and packages will be submitted to the FDA in a collaboration between regulatory scientists at UR and Duke. Working with manufacturers, the RC will qualify every DDT component before distribution to development teams. The RC will also advance DDTs to arrayed formats that are compatible with automated plate readers and liquid handlers. The AC will include an Executive Committee that will direct the Center with input from stakeholders, including pharmaceutical companies who will define end user needs. The AC will also manage formal reporting and other interactions with the NIH, FDA, and the NCATS center hub. The dysregulated transport of cells and molecules between tissues is the underlying cause of many diseases and is applicable to the development of drug programs. Additionally, the delivery of drugs to affected tissues depends on the ability to cross these barriers. Despite the fundamental significance of tissue barriers in medicine, most microphysiological systems (MPS) do not provide reliable access to quantitative assessments cellular and molecular exchanges at tissue barriers. By focusing on DDTs specially designed to provide these metrics, the TRaCe-bMPS addresses an unmet need in drug development. This focus, along with the unique technologies that enable it, will also make the TRaCe-bMPS a unique and valuable contributor to the forthcoming TRaCe-MPS network.

Narrative This project will establish the Translational Center for Barrier MPS (TRaCe-bMPS). The Center will create five device platforms focused on dysregulated barrier function in disease and seek FDA approval for each as a qualified drug development tool (DDT).