Ed Damiano’s lab has been engaged in basic scientific research that combines mathematical modeling, computational analysis, and experimental investigations across length scales ranging from macromolecular assemblies, cellular mechanics, and microscale biofluidics to cardiovascular fluid mechanics and the biomechanics of vestibular sensory systems. The lab’s previous work in microvascular research integrated fluid dynamics with intravital microscopy to study blood flow in the microcirculation and to elucidate mechanisms by which the lining of blood vessels determines vascular health and disease. In past research, the focus was on the glycocalyx, which forms a complex hydrated mesh of cell surface macromolecules that is situated at the interface between the luminal vascular wall and flowing blood. We developed new analytical and experimental tools to interrogate the glycocalyx in vivo and in vitro. We demonstrated that this layer of macromolecules retards plasma flow within ~500 nm from the vessel wall in healthy blood vessels, but is significantly degraded in the presence of vascular inflammation and chronic hyperglycemia. We also showed that the observed hydrodynamic properties of the glycocalyx in vivo are substantially absent from endothelial cells cultured under standard conditions in vitro.
Our current research is committed to creating and integrating blood-glucose control technologies with a vision of building a bihormonal (insulin and glucagon) bionic pancreas that his son could take with him to college. This endeavor began with the design and development of mathematical algorithm strategies for blood-glucose control, which we began testing in our laboratory at Boston University in 2005 in a swine model of type 1 diabetes. In 2006, we began working with our clinical collaborators at the Massachusetts General Hospital (MGH) to design their first clinical protocol. Between 2008 and 2012, we tested our system in the inpatient setting in one-day and two-day experiments in adults and adolescents with type 1 diabetes in the Clinical Research Center at the MGH. In late 2012 we received approval from the FDA to begin testing a mobile version of our system, which integrates an iPhone with our blood-glucose control algorithms, two insulin pumps (one for insulin and the other for glucagon), and a continuous glucose monitor. In 2013, we conducted the Beacon Hill Study with our clinical collaborators at MGH to test the iPhone version of our bionic pancreas in five-day experiments in 20 adults with type 1 diabetes in downtown Boston; it was, at the time, the most ambitious outpatient trial ever to test an autonomous ambulatory glucose control system. In the summers of 2013 and 2014, we conducted our 2013 and 2014 Summer Camp Studies with our clinical collaborators at MGH to test the iPhone version of their bionic pancreas in five-day experiments in 51 children 6 to 20 years old with type 1 diabetes at Camp Joslin and the Clara Barton Camp in central Massachusetts. Along with our clinical collaborators at MGH, the University of Massachusetts Medical Center, Stanford University, and the University of North Carolina, Chapel Hill, we recently completed the Bionic Pancreas Multicenter Study, in which we tested the iPhone version of their bionic pancreas in a home study in 40 adults with type 1 diabetes who used the device for 11 days at work and at home. Along with their industrial collaborators, our engineering team recently built the first fully integrated biohormonal bionic pancreas medical device that does not rely upon smartphone technology. We call this device the iLetTM, in homage to the pancreatic islets of Langerhans, which contain the alpha and beta cells that secrete glucagon and insulin. Our goal is to begin testing the iLet in clinical trials in the second half of 2016 and to begin the final pivotal trial testing the iLet in the early 2017.