Join us tomorrow Thursday, February 25th for a talk with
Dr. Jeffrey W. Holmes. Coffee, cookies and pizza are served.
For visitors from outside Mason – Parking is best in the Shenandoah Parking Garage ( Bldg. 43 on the campus map). The seminar will be in Research Hall, 163:
February 25th, 2016 from 12:30 PM – 1:30 PM
Research Hall 163
Speaker: Jeffrey W. Holmes, MD and PhD, Professor,
Dept. of Biomedical Engineering and Medicine, University of Virginia
Multi-Scale Modeling of Healing Myocardial Infarcts: Counterintuitive Predictions for Improving Post-Infarction Function
The mechanics of healing myocardial infarcts are a critical determinant of left ventricular function and the risk of an array of post-infarction complications including catastrophic rupture and progression to heart failure. Yet it has proven remarkably difficult to devise therapies to improve post-infarction prognosis by manipulating the scar formation process. Recent studies have helped explain why: collagen alignment is a more important determinant of LV function than collagen content or overall scar stiffness, the primary targets of most interventions. We recently showed that infarcts healing in different mechanical environments develop different collagen fiber structures and mechanical properties. We developed an agent-based model to evaluate the mechanisms by which mechanical environment directs collagen deposition and remodeling by cardiac fibroblasts and to better understand the effects of therapeutic interventions on the evolving scar structure. Parameters for this model were derived from a combination of published literature and new experiments in engineered tissue-equivalents, focusing particularly on features of cell-matrix interaction such as contact guidance and collagen remodeling. Our results suggest that different environmental cues regulate scar formation in different tissues. In contrast to previous models of skin wound healing showing that chemokine gradients are a dominant regulator of scar formation, we find that mechanical environment is the dominant regulator of evolving scar structure following myocardial infarction. Our results also predict that a number of regenerative and device therapies that alter infarct mechanics – including stem cell injection, polymer injection, surgical reinforcement, and peri-infarct pacing – will alter scar structure, in some cases reducing the efficacy of the therapy. Moving forward, computational models of infarct healing suggest unexpected, novel approaches to improving heart function.
Dr. Holmes is a Professor of Biomedical Engineering and Medicine at the University of Virginia. He obtained his B.S. in Biomedical Engineering from the Johns Hopkins University in 1989, his Ph.D. in Bioengineering from the University of California, San Diego in 1995, and his M.D. from the University of California, San Diego in 1998. Dr. Holmes currently teaches BME 6102 Engineering Physiology II: Organ Physiology, and Soft Tissue Mechanics / Finite Elasticity.
Academic Program Coordinator
Volgenau School of Engineering, Department of Bioengineering
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Phone: (703) 993-4190
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