Collaborative Research: Modular, vascularized microphysiological systems to study the outer blood retinal barrier

University Of Rochester, Rochester NY

Investigators

Abstract

Certain vascularized tissues such as the outer blood retinal barrier are difficult to study using animal models due to major physiological and anatomical differences. Microphysiological systems (MPS), also known as tissue chips, are an alternative to animal models that enable the study of complex tissue systems. MPS can incorporate patient specific stem cells for personalized medicine and are easily scalable for larger scale investigations. This project will support the development of a new MPS that controls physical, biochemical, and cell signaling cues to guide the development of microvascular tissues, including the cues needed for forming perfusable blood vessels. It is expected that successful completion of this work will provide a greater understanding of how physical, biochemical, and cell signaling cues guide microvessel development and establish an alternative to animal models for pre-clinical drug testing. This work will support the training of junior scientists from diverse backgrounds and prepare them for careers in research and education. The Investigators are proactive in working to increase diversity and expose high school students to possible STEM career opportunities. Further, findings that are made from this research will be shared through numerous outreach activities and programs including: Teach the Teachers, undergraduate and high school student mentorship, and speaking at public engagements such as the Annual Benoit Laboratory Alex’s Lemonade Stand. Advances in tissue engineering and tissue chip technology have catalyzed the rise of microphysiological systems (MPS) as an alternative to animal models for preclinical testing. MPS for vascularized tissues either forego perfused microvasculature or rely on oversimplified endothelial cell-lined fluidic channels. Microvascular tissues are 3D and have tissue specific molecular transport, angioarchitectural, and paracrine-tissue crosstalk properties. Engineered extracellular matrices (eECM) comprised of poly(ethylene glycol) (PEG) hydrogels crosslinked with matrix metalloproteinase (MMP)-degradable peptides and functionalized with cell adhesive ligands have been shown to support vasculogenesis. In this project, vasculogenic eECM will be introduced into a novel MPS designed for microvascular network development. Specifically, pressure/flow and eECM biophysical and biochemical cues will be explored to guide the development of in vivo-like perfusable microvasculature specific to bone, salivary gland, and the retina. Successful completion of the proposed aims will elucidate the role of flow in microvascular development, advance the development of MPSs, and augment our understanding of the eECM biochemical cues that mediate endothelial cell vasculogenesis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.