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.