Engineering 3D-Printed, Phototunable Models of Pulmonary Arterial Adventitia to Study Sex Differences in Fibroblast Activation

Welcome Dr. Chelsea Magin, Assistant Professor in the Departments of Bioengineering, Pediatrics and Medicine and the Principal Investigator of the Bio-inspired Pulmonary Engineering Laboratory at the University of Colorado, Denver, Anschutz Medical Campus.

Abstract:

Pulmonary arterial hypertension (PAH) is a form of a pulmonary vascular disease that causes high blood pressure in the lungs. It results in scarring of the small blood vessels, leading to impaired blood flow and increased blood pressure. Over time, this increase in blood pressure causes damage to the heart. This disease is four times more likely to impact women than men and women but the mechanisms underlying these sex differences remain unknown. Studies to improve our understanding of the mechanisms underlying sex differences in PAH could be accelerated by cell-culture tools that reproduce key aspects of human physiology, i.e., the complex 3D geometry of pulmonary vasculature and time-dependent changes in extracellular matrix mechanical properties that occur during disease progression. To overcome these limitations, we designed a novel biomaterial that is initially soft like healthy blood vessels and can be stiffened using light to mimic vessel scarring in PAH. The material is stable for long periods of time in the conditions used to grow cells and can be 3D bioprinted with cells inside to reproduce the shape of a pulmonary blood vessel. Experiments have demonstrated that stiffening in 3D results in activation of male cells but that cells derived from female patients are not as sensitive to changes in the microenvironment.

Her team develops bio-inspired, engineered cell culture platforms that precisely and consistently recapitulate the dynamic extracellular microenvironment and complex 3D micro-architecture of lung tissue. These bioengineered models enable her team to study lung disease and regeneration. Dr. Magin has extensive experience in the conception, development and translation of medical devices into commercial products. As the Director of Product Development for Sharklet Technologies, Inc. she led a research and development team that designed medical devices that use the Sharklet surface texture to control biological adhesion. Dr. Magin earned her BS with highest distinction in Materials Science and Engineering from the University of Florida in 2006 with internship experience at Kimberly-Clark Corporation. This was followed by an MS and PhD in Biomedical Engineering from the University of Florida with Dr. Anthony Brennan in 2008 and 2010, respectively. Her doctoral research focused on developing biomaterials to control adhesion of both marine fouling organisms and mammalian cells. During her graduate work Dr. Magin was both a University of Florida Alumni Fellow and a Clare-Booth Luce Graduate Fellow. She also completed an NIH Postdoctoral Fellowship at the University of Colorado, Boulder in the Anseth Research Group where she developed user-controlled, dynamically tunable biomaterials to study mesenchymal stem cell differentiation, and the progression of heart disease in a valvular interstitial cell model.

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