TISSUE ENGINEERED MODELS TO STUDY THE BLOOD-BRAIN BARRIER, TUMOR MICROENVIRONMENT, DRUG DELIVERY SYSTEMS, AND MORE
The blood-brain barrier (BBB). The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system and protects the central nervous system from potentially harmful chemicals while regulating transport of essential nutrients. We are using tissue engineering, stem cell technology, and microfabrication to reverse engineer the blood-brain barrier. Reverse engineering is the process of understanding the function of individual components in anything man-made (usually through disassembly), to enable reproduction. This reductive approach to understanding the role of individual components is particularly well suited for the BBB, which is inherently complex and involves multiple cell types. In particular it allows us to elucidate the underlying physical and biochemical processes that regulate the phenotype of brain capillaries and microvessels, while simultaneously allowing us to systematically increase the complexity of the model.
In vitro models of the tumor microenvironment. Metastasis, which is responsible for more than 90% of cancer-related deaths, involves a sequence of steps including invasion, dormancy, intravasation, arrest, extravasation, and colonization at a secondary site. These are dynamical processes that occur at or near the vascular system and are very difficult to visualize in vivo. Our incomplete understanding of the steps in the metastatic cascade is a major barrier to developing therapies to prevent the spread of the disease and improve patient outcomes. Recent advances in the development of in vitro microvessel models provide the tools to create more physiological models of the tumor microenvironment and to visualize steps in the metastatic cascade. We are developing tissue-engineered models of the tumor microenvironment to visualize steps in the metastatic cascade. These models include tumor vasculature, post-capillary venules, and capillary networks. These models are also being used for testing and imaging drug and gene delivery vehicles.
Modeling diverse diseases. Vascular influences on diseases of every organ system are increasingly key to understanding the progression of disease and developing therapeutics that target key dysfunction. However, many sensitive tissue sites prevent in vivo advanced study of the vasculature and its effect on surrounding parenchyma. Utilizing our in vitro microvascular platform, we are able to recapitulate key geometric, chemical, and biological contributors to disease and study its impact on the vasculature withhigh spatiotemporal resolution. Currently, we are developing and studying models of infectious disease and neurodegenerative disease to assess the activity of vascular barrier loss, blood-tissue exchange, and other functional changes in response to the disease state.
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