Computations and Modeling

Break any bone in the human body and the body can repair the tissue and fix the damage. Yet tooth enamel — the strongest tissue in the human body — cannot repair itself. Still, our teeth last a lifetime.

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Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Mantle cell lymphoma is considered incurable, even though new treatments have yielded promising results.

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Study: A bioengineering group from the University of Pittsburgh Swanson School of Engineering is bringing the worlds of computational modeling and experimentation closer together by developing a methodology to help analyze the wealth of imaging data provided by advancements in imaging tools and automated microscopes.

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The University of Pittsburgh School of Medicine and Carnegie Mellon University each have been awarded four-year contracts totaling more than $7.2 million from the U.S. Department of Defense to create an autonomous trauma care system that fits in a backpack and can treat and stabilize soldiers injured in remote locations.

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Collaboration and competition are basic instincts among biological species, from the simplest single-celled organisms to reptiles, fish and primates, as well as humans. This dynamic behavior – the result of millions of years of evolution – is difficult to replicate in synthetic systems. However, chemical engineers at the University of Pittsburgh Swanson School of Engineering have recreated these responses in an environment of microscopic particles, sheets, and catalysts, effectively mimicking responses of feeding, fighting, and fleeing.

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McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, has been at the Swanson School of Engineering since 1987 and is now a Distinguished Professor in chemical and petroleum engineering.  As reported by Amerigo Allegretto for Pittwire, Dr. Balazs is working to transform the future through her research of soft robotics, which could have revolutionary applications across a variety of fields — from surgery in hospitals to rehabilitating patients to providing safer industrial manufacturing conditions.

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The “magic carpet” featured in tales from “One Thousand and One Nights” to Disney’s “Aladdin” captures the imagination not only because it can fly, but because it can also wave, flap, and alter its shape to serve its riders. With that inspiration, and the assistance of catalytic chemical reactions in solutions, a team from the University of Pittsburgh’s Swanson School of Engineering has designed a two-dimensional, shape-changing sheet that moves autonomously in a reactant-filled fluid.

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The University of Pittsburgh research team of

• Piervincenzo Rizzo, PhD, associate professor of civil and environmental engineering,
• Samuel Dickerson, PhD, assistant professor of electrical and computer engineering, and
• McGowan Institute for Regenerative Medicine affiliated faculty member Ian Conner, MD, PhD, assistant professor of ophthalmology and bioengineering,

recently received funding via a $360,000 grant from the National Science Foundation.  Dr. Rizzo and his team are currently measuring the internal pressure of objects, such as a piece of steel girder and a tennis ball, with the end goal of calculating corrosive deterioration in pipelines in the natural gas, hazardous liquid and liquefied natural gas plant industries.  Other applications being researched for this technology include, most notably, for measuring and monitoring eye pressure in glaucoma patients.

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McGowan Institute for Regenerative Medicine affiliated faculty member Shilpa Sant, PhD, Assistant Professor of Pharmaceutical Sciences, has received a 7-year R37 MERIT Award from the National Cancer Institute (NCI), NIH, for her project entitled, “Three-dimensional organoid models to study breast cancer progression.” This grant is funded by the NCI under the Cancer Tissue Engineering Collaborative (TEC) Research Program that aims to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. The total funding for the first 5 years is $2.7 million.

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Buprenorphine (BUP) is approved for the treatment of opioid addiction. The current dosing regimen of BUP in pregnant women is based on recommendations designed for non-pregnant adults, but physiological changes during pregnancy may alter BUP exposure and efficacy.

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Embedding a decision support tool in the hospital electronic health record increases detection of acute kidney injury, reducing its severity, and improving survival, according to new research from the University of Pittsburgh and UPMC.

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The National Institutes of Health (NIH) has awarded a $1.2 million grant to a multi-institutional project led by the University of Pittsburgh to engineer a 3-dimensional joint-on-a-chip called the “microJoint,” to replicate a human joint on a small scale. The microJoint will be used to study and test drugs for the treatment of arthritic joint diseases. McGowan Institute for Regenerative Medicine associate director Rocky Tuan, PhD, is the principal investigator of the award.

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Molecular chelating agents are used in many areas ranging from laundry detergents to paper pulp processing to precious metal refining. However, some chelating agents, especially the most effective ones, do not degrade in nature and may pollute the environment. With support from the National Science Foundation (NSF), researchers at the University of Pittsburgh Swanson School of Engineering are developing machine learning procedures to discover new chelating agents that are both effective and degradable.

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“When there are one or two bacteria, they behave in a certain way,” said McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, Distinguished Professor of Chemical Engineering and the John A. Swanson Chair of Engineering at the University of Pittsburgh’s Swanson School of Engineering. “But suddenly, when there is a critical threshold of bacteria, the bacteria can sense this increase in population and they dramatically change their behavior.”

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McGowan Institute for Regenerative Medicine affiliated faculty members at the University of Pittsburgh have been awarded grants from the National Science Foundation (NSF) and the National Institutes of Health (NIH) to study diverse aspects of how the brain works.

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From the smallest cell to humans, most organisms can sense their local population density and change behavior in crowded environments. For bacteria and social insects, this behavior is referred to as “quorum sensing.” Researchers at the University of Pittsburgh’s Swanson School of Engineering have utilized computational modeling to mimic such quorum sensing behavior in synthetic materials, which could lead to devices with the ability for self-recognition and self-regulation.

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The National Science Foundation recently awarded a 3-year, $300K grant entitled, “SusChEM: machine learning blueprints for greener chelants.”  McGowan Institute for Regenerative Medicine affiliated faculty member Eric Beckman, PhD, Bevier Professor of Engineering in the Chemical Engineering Department at the University of Pittsburgh and a Co-Director of the Mascaro Center for Sustainable Innovation, is the project co-principal investigator along with principal investigator John Keith, PhD, R.K. Mellon Faculty Fellow in Energy, Department of Chemical Engineering.  The award begins August 1, 2017, and extends through July 31, 2020.

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McGowan Institute for Regenerative Medicine Director William Wagner, PhD, Professor of Surgery, Bioengineering and Chemical Engineering at the University of Pittsburgh, Chairman of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) – Americas, Deputy Director of the NSF Engineering Research Center on Revolutionizing Metallic Biomaterials, and Chief Scientific Officer of the Armed Forces Institute of Regenerative Medicine, was a member of the keynote panel of the recently held RAPID + TCT, North America’s preeminent event for discovery, innovation, and networking in 3D manufacturing.

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The U.S. Department of Defense recently announced the awarding of their 2017 large, multi-university grants in their MURI program.  One of the 23 awards will go to a team of researchers led by McGowan Institute for Regenerative Medicine affiliated faculty member Anna Balazs, PhD, Distinguished Professor of Chemical Engineering and the Robert v. d. Luft Professor, Department of Chemical & Petroleum Engineering, University of Pittsburgh.  Dr. Balazs will serve as the PI on the project entitled “Adaptive Self‐Assembled Systems:  Exploiting Multifunctionality for Bottom‐up Large Scale Engineering” with the team spanning the University of Pittsburgh, Harvard, Northwestern, and the University of Illinois.  The award is for 5 years at $1.5 million per year.

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Capitalizing on previous studies in self-powered chemo-mechanical movement, researchers at the University of Pittsburgh’s Swanson School of Engineering and Penn State University’s Department of Chemistry have developed a novel method of transporting particles that utilizes chemical reactions to drive fluid flow within microfluidic devices. Their research, “Harnessing catalytic pumps for directional delivery of microparticles in microchambers,” was published recently in the journal, Nature Communications.

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The work of McGowan Institute for Regenerative Medicine affiliated faculty members Ruben Zamora, PhD, Research Associate Professor at the University of Pittsburgh in the Department of Surgery, and Yoram Vodovotz, PhD, Professor in the Department of Surgery with secondary appointments in the Department of Computational & Systems Biology, the Department of Bioengineering, the Department of Immunology, the Department of Communication Science and Disorders (of the School of Health and Rehabilitation Science), and the Clinical and Translational Science Institute, and also the Director of the Center for Inflammation and Regenerative Modeling at the McGowan Institute, is featured in the November 2016 issue of the publication, Molecular Medicine.

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For as long as scientists have been listening in on the activity of the brain, they have been trying to understand the source of its noisy, apparently random, activity. In the past 20 years, “balanced network theory” has emerged to explain this apparent randomness through a balance of excitation and inhibition in recurrently coupled networks of neurons. A team of scientists has extended the balanced model to provide deep and testable predictions linking brain circuits to brain activity.

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Visual hallucinations … everyone has heard of them, and many people have experienced the sensation of “seeing” something that isn’t there. But studying the phenomenon of hallucinations is difficult: they are irregular, transitory, and highly personal—only the person experiencing the hallucination knows what he or she is seeing, and representations of what’s being seen are limited to verbal descriptions or drawings.

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As additive manufacturing, or 3D printing, continues to advance in industry and academia, knowledge gaps can appear as researchers push the technology to new limits. To solve some of industry’s most difficult additive manufacturing problems, Oberg Industries and the University of Pittsburgh’s Swanson School of Engineering have partnered to combine Oberg expertise in manufacturing complex tooling and precision machined or stamped metal components with Pitt’s ANSYS Additive Manufacturing Research Laboratory (AMRL).  McGowan Institute for Regenerative Medicine faculty member David Vorp, PhD, Associate Dean for Research, Swanson School of Engineering, William Kepler Whiteford Professor of Bioengineering, Director of the Center for Vascular Remodeling and Regeneration, Co-Director of the Center for Medical Innovation, and Director of the Vascular Bioengineering Laboratory, is a member of the Pitt team.

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The National Heart, Lung, and Blood Institute of the National Institutes of Health has awarded McGowan Institute for Regenerative Medicine affiliated faculty member Robert Parker, PhD, Professor in the University of Pittsburgh’s Department of Chemical and Petroleum Engineering, member of the Molecular Therapeutics/Drug Discovery Program at the University of Pittsburgh Cancer Institute, and a member of the Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center in the Department of Critical Care Medicine at the University of Pittsburgh, and, secondary Chemical and Petroleum Engineering faculty member Timothy Corcoran, PhD, a U01 Award.  The Award work is entitled “Building Multilevel Models of Therapeutic Response in the Lungs.”  The total amount funded will be $1.7M.

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The potential to develop “materials that compute” has taken another leap at the University of Pittsburgh’s Swanson School of Engineering, where researchers for the first time have demonstrated that the material can be designed to recognize simple patterns. This responsive, hybrid material, powered by its own chemical reactions, could one day be integrated into clothing and used to monitor the human body or developed as a skin for “squishy” robots.

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McGowan Institute for Regenerative Medicine Associate Director Rocky Tuan, PhD, has received a research grant from the Center for the Advancement of Science in Space (CASIS) to continue his work on a 3D microphysiological system (MPS) to be conducted on board the International Space Station (ISS) to evaluate the accelerated aging and degeneration process of bones that occurs in space.

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Researchers at the University of Pittsburgh Cancer Institute (UPCI) and materials and biomedical engineers at Carnegie Mellon University (CMU) including McGowan Institute for Regenerative Medicine affiliated faculty member Adam Feinberg, PhD, associate professor in CMU’s departments of Materials Science and Engineering and Biomedical Engineering, will address the overdiagnosis and overtreatment of a non-invasive precancerous breast tumor by creating the first-ever 3D bioprinted breast ductal structure to identify markers for low-risk premalignant disease.

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A novel investigation of how enzymatic reactions can direct the motion and organization of microcapsules may point toward a new theory of how protocells – the earliest biological cells – could have organized into colonies and thus, could have ultimately formed larger, differentiated structures.

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At the University of Pittsburgh, Yoram Vodovotz, PhD, is a professor in the Department of Surgery with secondary appointments in the Department of Computational & Systems Biology, the Department of Bioengineering, the Department of Immunology, the Department of Communication Science and Disorders (of the School of Health and Rehabilitation Science), and the Clinical and Translational Science Institute. He also is the director of the Center for Inflammation and Regenerative Modeling at the McGowan Institute for Regenerative Medicine.  In this latter role, his research interests, carried out in the context of an interdisciplinary research team, include systems biology and mathematical modeling of inflammation and wound healing in various disease states, especially infection, trauma/hemorrhage, wound healing, and liver failure, as well as the application of these computational approaches (i.e. in silico) to regenerative medicine, biomarker discovery, and rational drug/device design.  In silico study in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials.

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Combining photo-responsive fibers with thermo-responsive gels, researchers at the University of Pittsburgh’s Swanson School of Engineering and Clemson University have modeled a new hybrid material that could reconfigure itself multiple times into different shapes when exposed to light and heat, allowing for the creation of devices that not only adapt to their environment, but also display distinctly different behavior in the presence of different stimuli.

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Researchers at the University of Pittsburgh are part of a multicenter team that has been awarded a $6.4 million, 3-year federal grant to figure out how the animal nose knows how to localize the smell of mates, food, and other significant scents. The co-principal investigators of the Pitt arm of the effort are McGowan Institute for Regenerative Medicine affiliated faculty member Bard Ermentrout, PhD, Distinguished University Professor of Computational Biology, a Professor of Mathematics, and an Adjunct Professor of Neurobiology at Pitt, and Nathan Urban, PhD, Professor in the Department of Neurobiology at Pitt School of Medicine and Associate Director of the University of Pittsburgh Brain Institute.

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McGowan Institute for Regenerative Medicine affiliated faculty member Anna C. Balazs, PhD , Distinguished Professor of Chemical and Petroleum Engineering, and Steven P. Levitan, PhD , John A. Jurenko Professor of Electrical and Computer Engineering, integrated models for self-oscillating polymer gels and piezoelectric micro-electric-mechanical systems to devise a new reactive material system capable of performing computations without external energy inputs, amplification, or computer mediation.

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Computer Simulation Predicts Development, Progress of Pressure Sores

Researchers at the University of Pittsburgh School of Medicine have devised a computational model that could enhance understanding, diagnosis, and treatment of pressure ulcers related to spinal cord injury. In a report published online in PLOS Computational Biology, the team also described results of virtual clinical trials that showed that for effective treatment of the lesions, anti-inflammatory measures had to be applied well before the earliest clinical signs of ulcer formation.

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“We’ve had a long history of using machine learning to assess the instability of patients in the hospital,” said McGowan Institute for Regenerative Medicine affiliated faculty member Michael Pinsky, MD, professor of critical care medicine, bioengineering, anesthesiology, cardiovascular diseases, and clinical/translational services at the University of Pittsburgh School of Medicine. “In one such study, we analyzed noninvasive vital signs such that alerts would go off if the monitor value was outside the normal range,” he said. “And using an artificial neural net, we were able to identify stable from unstable, good from bad. This current study is an extension of that work.”

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Traumatic injury is a major health care problem worldwide. Trauma induces acute inflammation in the body with the recruitment of many kinds of cells and molecular factors that are crucial for tissue survival, explained senior investigator Dr. Vodovotz. But if inappropriately sustained, the inflammatory response can compromise healthy tissues and organs.

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The biomolecule sorting technique was developed in the laboratory of Joanna Aizenberg , PhD, Amy Smith Berylson Professor of Materials Science at Harvard School of Engineering and Applied Sciences (SEAS) and Professor in the Department of Chemistry and Chemical Biology . Dr. Aizenberg is also co-director of the Kavli Institute for Bionano Science and Technology and a core faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering , leading the Adaptive Materials Technologies platform there.

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Designing a Synthetic Gel that Changes Shape and Moves via Its Own Internal Energy

For decades, robots have advanced the efficiency of human activity. Typically, however, robots are formed from bulky, stiff materials and require connections to external power sources; these features limit their dexterity and mobility. But what if a new material would allow for development of a “soft robot” that could reconfigure its own shape and move using its own internally generated power?

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A Strategy for Stimulating Heart Muscle Regeneration in Infants, Study Finds

Surgery often is life-saving for many infants born with heart defects, but one thing that doctors cannot do yet is replace heart muscle that is scarred and dysfunctional.  McGowan Institute for Regenerative Medicine affiliated faculty member Bernhard Kühn, MD, director of research for the Division of Cardiology at Children’s Hospital, and associate professor of pediatrics at the University of Pittsburgh School of Medicine, and researchers from the Heart Institute at Children’s Hospital and Boston Children’s Hospital hope to overcome the challenge by stimulating regeneration of heart tissue. The findings were described in Science Translational Medicine.

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Older age is a well-known risk factor for IPF, a disease in which the lung tissue becomes progressively fibrotic, or scarred, leading to breathing difficulties and death within 3 to 5 years if a lung transplant isn’t possible, said senior investigator Ana L. Mora, MD, assistant professor in the Division of Pulmonary, Allergy and Critical Care Medicine and a member of the Heart, Lung, Blood and Vascular Medicine Institute (VMI) at Pitt. The cause of the disease is unknown, or “idiopathic.”

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