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Next seminar:
"Redox Mechanisms of Coronary Control"
Mr. William Chilian, Northeastern Ohio University
Friday, December 4, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building
Abstract
Redox mechanisms play a critical role in the functions of many cellular processes. Yet despite this importance, the exact role of redox mechanisms in the governance of acute and chronic adaptations of the coronary circulation are largely unappreciated. In this context, this seminar will provide information about how redox mechanisms are involved in acute regulation regulation of blood flow to the heart-that is beat to beat regulation-in the coupling of flow to metabolism in a feed-forward pathway. Also redox mechanisms in the chronic adaptation of the coronary circulation to myocardial ischemia will be also discussed.
Bioengineering Seminar Schedule, Fall 2009
Final Defense - “Quantitative Analysis of Peristaltic and Segmental Motion in vivo in the Rat Small Intestine Using Dynamic MRI and Image Analysis”
Amit Ailiani, Penn State
Friday, August 28, 2009, 12:00 - 1:00 pm, Room 210 Hallowell Building, CG628 Hershey
Abstract
Conventional methods of quantifying segmental and peristaltic motion in animal models are highly invasive; involving, for example, the external isolation of segments of the gastrointestinal (GI) tract either from dead or anesthetized animals. The present study was undertaken to determine the utility of MRI to quantitatively analyze these motions in the jejunum region of anesthetized rats (N = 6) noninvasively. Dynamic images of the GI tract after oral gavage with a Gd contrast agent were acquired at a rate of six frames per second, followed by image segmentation based on a combination of three-dimensional live wire (3D LW) and directional dynamic gradient vector flow snakes (DDGVFS). Quantitative analysis of the variation in diameter at a fixed constricting location showed clear indications of both segmental and peristaltic motions. Quantitative analysis of the frequency response gave results in good agreement with those acquired in previous studies using invasive measurement techniques. PCA of the segmented data using ASM resulted in three major modes. The individual modes revealed unique spatial patterns for peristaltic and segmental motility. PCA results suggest that the neurophysiology underlying the control of motility can be considered much simpler; for example segmental vs. peristaltic wave patterns must be represented primarily by the phase relationships among the principal components. MRI results also show that inactin anesthesia does not have the same inhibitory effects on the gut motility as isoflurane, confirming indirect data in the literature acquired using invasive techniques, but also adding detailed knowledge of the changes in gastrointestinal motions produced by these anesthetics.
“Mediation of Leukocyte-Endothelial Adhesion by Matrixmetallo-Proteases (MMPs)“
Dr. Herbert Lipowsky, BioEngineering, Penn State
Wednesday, September 2, 2009, 12:00 - 1:00 pm, Room 210 Hallowell Building, CG624E Hershey
Abstract
The kinetics of leukocyte-endothelial adhesion has been well documented in terms of the radial migration of WBCs to the surface of post-capillary venules, their subsequent selectin mediated rolling on the endothelium (EC) and their integrin mediated adhesion to the EC. The present studies explore the hypothesis that MMPs play a significant role in WBC-EC adhesion by cleavage of proteoglycans and GAGs from the EC glycocalyx. MMP induced shedding of glycans from the glycocalyx may expose adhesion molecules (e.g. ICAM-1) to result in a rapid onset of WBC-EC adhesion, as for example, elicited by superfusion of rat mesentery with the chemoattractant fMLP. The present studies demonstrate that superfusion of the tissue with either the broad spectrum MMP inhibitor doxycycline or the zinc chelator ilomastat inhibit onset of adhesion in response to fMLP. Activation of MMPs by fMLP induced signaling was further substantiated by cleavage of circulating MMP fluorescent substrates on the EC luminal surface. Thus, sub-antimicrobial doses of doxycyline may be of clinical value as a therapeutic treatment for inflammation. Further, WBC-EC adhesion may be governed by latent MMPs resident in the endothelial surface layer awaiting activation by an inflammatory stimulus.
“Engelmayr Lab for Tissue Engineering and Regenerative Medicine: A Research Progress Update"
Dr. George Englemayr, BioEngineering, Penn State
Wednesday, September 9, 2009, 12:10 - 1:00 pm, Room 210 Hallowell Building
Abstract
The over-arching goal of research in the Engelmayr Lab is to contribute toward the development of functional engineered tissues for basic science and regenerative medicine applications.
Aspects of our interdisciplinary work include:
(A) tissue specific scaffold design and fabrication for promoting the development of biomimetic tissue properties,
(B) bioreactor design and use in studying biophysical and biochemical control of engineered tissue formation and stem cell differentiation, and
(C) mathematical modeling to integrate the fruit of experimentation into a cohesive predictive framework.
In this research progress update I will present our progress on a selection of our current research projects and associated presentation and funding plans.
Projects to be discussed include (among others): (1) structural-mechanical modeling of microfabricated elastomeric scaffold for cardiac muscle tissue engineering, (2) endocardial endothelial cell modulation of tissue engineered cardiac muscle response to fluid shear stress, and (3) cardiomyogenic differentiation of spermatogonial stem cells in response to myocardial-mimetic biophysical and biochemical cues.
“BioMEMS Technology for Cancer Metastasis and Body Fluid Analysis: A Research Progress Update for PSU MINIBio Lab”
Dr. Siyang Zhang, BioEngineering, Penn State
Wednesday, September 16, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG628 Hershey
Abstract
The PSU Micro & Nano Integrated Biosystem Lab (MINIBio) aims at developing micro and nano enabled technologies for biomedical applications and using these technologies for biological research. We are trying to use new materials and develop novel fabrication processes for unique bio applications. We want to build up a multidisciplinary research team and collaborate with various groups in different fields on campus and across the nation.
Our current efforts are mainly focused on BioMEMS technology development and its applications in two areas: cancer metastasis and body fluid analysis.
1. For BioMEMS technology development, we are working on both in vivo and in vitro microdevice platforms.
2. In application area cancer metastasis, we are interested in developing enrichment technology for circulating tumor cells and studying their properties for prognosis, diagnosis, and treatment monitoring and removing them as a therapeutic approach.
3. In application area body fluid analysis, the main target is blood. The long term goal is to build technology platform to separate each individual components and analyze multiple targets simultaneously.
Round Table Discussion on PhD Course Requirements and Candidacy Exam Policies
Dr. Herbert Lipowsky, Bioengineering, Penn State
Wednesday, September 23, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG628 Hershey
Abstract
Round table discussion on PhD course requirements and the candidacy exam policies.
"Medical Devices for Kenya and the Internationalization of Bioengineering"
Dr. Peter Butler, Bioengineering, Penn State
Special guests: Dr. Maggie Slattery, Brittany Flaherty, Michael Fickes, Stefanie Auf Der Mauer and Michael Perone
Wednesday, September 30, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E Hershey
Abstract
In the summer of 2009, a group of about 12 students and 3 faculty members from Penn State traveled to Nyeri, Kenya to implement a telemedicine system called “Mashavu” (meaning “chubby cheeked” in Swahili). This project represented the culmination of a large interdisciplinary effort toward social entrepreneurship through biomedical device design. This seminar will describe how Mashavu, and the biomedical devices designed for it, helped motivate undergraduate bioengineering students to integrate design methods and advanced computational techniques in engineering in the design process. It will also highlight how these efforts align with Penn State’s efforts in the internationalization of education and the College of Engineering’s goal of training “world class engineers.”
Final Defense - "Blood Flow in End-to-Side Anastomoses of Ventricular Assist Devices"
Ning Yang, Penn State
Thursday, October 1, 2009, 2:00 pm, Room 210 Hallowell Building, CG628 Hershey
Abstract
Although there are many studies that focus on the fluid mechanics within ventricular assist devices (VADs), the impact of VAD anastomoses on the aortic flow has been largely ignored. Hence, we study the blood flow within the end-to-side anastomoses of VADs to adult and pediatric aortas. The great vessels originating from the aortic arch are included to study flow splitting. A second-order accurate time-dependent flow solver based on finite volume method is used to simulate the flow. Monotone integrated large eddy simulation is used to resolve large scales of the resulting turbulent flow based on grid cut-off and to model the sub-grid scale (SGS) motions using non-linear built-in (implicit) SGS turbulence models. Hemolysis is modeled using an advection-reaction transport equation. The flow solver is validated against analytical and experimental results. The effect of blood viscoelasticity is examined experimentally using particle image velocimetry. Our results suggest that the VAD anastomoses significantly alter the flow in the aorta. A proximal anastomotic configuration diverts an impingement jet into the brachiocephalic artery and may increase the perioperative right-sided stroke rate, whereas a distal anastomotic configuration leads to a large stagnant flow region near the aortic valve and possible thrombosis. Turbulence occurs for both configurations during the complete VAD support. The continuous support significantly reduces the blood damage in the aorta when compared to the pulsatile support, although it could lead to end-organ failure as a result of the reduced pulsatility. This work may help to identify the risk of graft failure for patients with VAD assistance.
No Seminar - BMES Conference
October 9, 2009
"ABIOMED Blood Pumping Technologies: Recovering Hearts… Saving Lives"
Scott Corbett, Abiomed
Wednesday, October 14, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E Hershey
Abstract
Background of the Company and product overview is discussed with focus on the Impella 2.5 catheter based rotary flow pump, AB5000 ventricular assist device and AbioCor totally implanted artificial heart. Interactions with the human body are highlighted including blood compatibility, anatomic fit, and physiological control.
"A Novel Treatment for Coronary Artery Disease: Focus on the Microcirculation"
John Pacella, University of Pittsburgh
Wednesday, October 21, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E Hershey
Abstract
Drag reducing polymers (DRPs) are linear, blood soluble macromolecules that reduce fluid friction in turbulent flow and provide a higher flow for a given driving pressure. Using myocardial contrast echocardiography (MCE) and radio labeled microsphere flow analysis, we have previously shown that DRPs reduce microvascular resistance and improve myocardial capillary perfusion in a canine model of severe LAD coronary artery stenosis. In an effort to discern the microvascular level in which DRPs exert their primary flow enhancing effect, we used mathematical modeling and MCE and determined that DRPs lowering capillary resistance and increase capillary blood volume. To further uncover the mechanism of action of these intriguing polymers, we used intravital microscopy of the rat cremaster muscle microcirculation to study microvascular hemodynamics during DRP infusion. We found that DRPs increased microvasular RBC velocity in all three microvascular compartments. In addition, we found that DRPs were associated with a 10% increase in arteriolar diameter. Since vasodilation could also explain their resistance lowering and flow enhancing effects, we attempted to pharmacologically control vasomotor tone in 2 different animal models. We then determined whether DRPs had additional resistance lowering effects. These studies were conducted in rabbit in which we locally infused adenosine to cause maximal VD and then infused DRP measured R to determine whether there was a further reduction. Then, in rats, to exclude changes caused by nitric oxide (NO), we used LNAME to block endogenous NO and cause VC. DRP infusion was again found to cause a further reduction in VR. Interestingly, in 2 different animal species employing 2 different pharmacologic means to control vascular tone, the DRP-induced magnitude of resistance reduction was similar at 14%. The current mechanistic investigations of DRPs are centered around determining whether DRPs enhance microvascular perfusion via favorable alterations in blood flow hydrodynamics or whether DRPs enhance the distribution of RBCs within the microcirculation. To address the former, the servonull micopressure technique will be brought to bear on this question as we will attempt to cannulate precapillary arterioles to determine whether DRPs increase capillary driving pressure. Thus, DRPs appear to not only have tone-independent resistance lowering effects, but also, they favorably alter the microvascular distribution of RBCs. Both of these properties could have important therapeutic implications for any condition that results in compromised microvascular perfusion.
"Applications of Transport Principles in Tissue Engineering: Design and Development of Tissue Constructs with Built-In Microvasculature"
Hari Baskaran, Case Western University.
Wednesday, October 28, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E Hershey
Abstract
This seminar will address the design and development of tissue engineered constructs with built-in microvasculature. Tissue engineering has the potential to revolutionize healthcare. Of several tissue-engineered products under development, only a few, targeting the musculoskeletal system, are currently approved for clinical use. Transport limitations play a major role in developing products that target tissues of vital organs such as the liver, pancreas, heart and lungs. The strategic goal of our laboratory is to fabricate tissue engineered products with built-in microvasculature. We have developed an approach to design tissue-engineered constructs with built-in microvasculature. Here, we discuss the rational design and development of model microvascular networks that can be integrated in biomaterials. By choosing skin as the tissue model and bifurcating flow channels as the fluid transport design, an optimization model was developed and solved to obtain flow network designs with optimal transport characteristics. We characterize fluid and mass transport in these networks using experimental and computational techniques. Furthermore, a new collagen-lithography technique was developed to transfer the network designs from the computer onto collagen-glycosaminoglycans biopolymeric matrices, enabling future studies on the efficacy of integrated flow in skin tissue engineering.
"Regenerative Medicine from an Industry Perspective"
Mr. Russ Kronengold, Kensey Nash
Friday, November 6, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E
Topic TBA
Mr. Jeff Garanich, Boston Scientific
November 11, 2009: POSTPONED
"Patient-specific Blood Systems Biology"
Mr. Scott Diamond, University of Pennsylvania
Wednesday, November 18, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E
Abstract
The dynamics of thrombosis depend on prevailing hemodynamics in conjunction with biochemical determinants at the injury site (i.e. tissue factor, vWF, and collagen) along with prevailing biological attributes of the flowing blood. Fluid flow affects: platelet fluxes to the wall, the time available to form bonds, force loading of bonds, cellular deformation, endothelial metabolism, and removal of reactive species created during thrombotic events. We have deployed a variety of techniques in microfluidics and combinatorial high throughput phenotyping of platelet and coagulation function to drive hierarchical Systems Biology models of platelet metabolism and thrombus buildup under flow.
No Seminar - Fall Break
November 27, 2009
"Redox Mechanisms of Coronary Control"
Mr. William Chilian, Northeastern Ohio University
Friday, December 4, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building
Student Presentations
E. Hayden, G. Long, D. Ahmed and M. Lapsley
Friday, December 11, 2009, 12:10 - 1:15 pm, Room 210 Hallowell Building, CG624E Hershey
“Pulsatile Gradient Generation via Acoustic Streaming of Bubbles”
by: Daniel Ahmed
Advisor: Tony J Huang
Abstract
Gradients of biochemical solutions are important in various biological processes. Recent studies have shown that both magnitude and timing of chemical stimulus play an important role in cell behavior. We have developed an active microfluidic gradient generator via acoustic streaming of oscillating bubbles. The bubbles are acoustically turned on/off via a transducer connected to a function generator, allowing both stable and pulsatile gradient generation. Furthermore, the oscillation of bubbles can be tuned directly by controlling the voltage, allowing various dynamic chemical profiles. This concept is inspired by mixing two chemical species by an oscillating bubble trapped in a horse-shoe structure. When acoustically driven, the membranes (liquid/air interfaces) of these trapped bubbles started to oscillate. The bubble oscillation resulted in a microstreaming phenomenon—strong pressure and velocity fluctuations in the bulk liquid, thus giving rise to fast and homogenized mixing of two side-by-side flowing fluids. To achieve biomolecular pulsatile gradient, five horse-shoe structures are designed in a ladder shape. As fluids (stimulant and buffer) are introduced into the device, bubbles get trapped within the horse-shoe structure and a laminar flow is established. By subsequent mixing and merging of fluid along and across the channel, a stable linear gradient profile is established. The performance of the gradient generation was characterized by deionized water and ink. Linear gradient profiles and other pulsatile profiles and its stability are investigated. We believe our spatiotemporal gradient generation will allow investigation of cell signaling under various pulsatile chemical profiles.
“Abnormalities in Reactive Hyperemia in Diabetics and its Diagnostic Potentials”
by: Eileen Hayden
Advisor: Dr. Herbert H Lipowsky
Abstract
Recent studies have analyzed the microcirculation in diabetic patients to determine any abnormalities which might indicate certain complications that can arise from diabetes. The objective was to assess the post-occlusive reactive hyperemia in normal and diabetic subjects. The trend was that diabetic patients took longer to recover from the occlusion than normal subjects. However these studies did not asses the hyperemic loop created from a perfusion vs. velocity profile as well as the loop created from the concentration of moving blood cells (CMBC) vs. velocity. The object of this study was to find a more quantitative parameter to analyze the hyperemic response and to determine its feasibility as a diagnostic tool for early changes in the microcirculation. Perfusion, velocity, and CMBC were measured on the subjects’ finger using laser doppler flowmetry. Three trials of reactive hyperemic responses were recorded from each subject at room temperature with the occlusion lasting only 10 seconds. The data was analyzed by calculating the circularity ratio (CR) of the hyperemic response of both the perfusion and CMBC curves.
“Optofluidics: Integrated Optical Devices in Microfluidics”
by: Michael Lapsley
Advisor: Tony J Huang
Abstract
Optofludics is an emerging field which integrates micro-optical systems with microfluidic networks. The combination of these two field leads to a number of innovative microscale devices. My first experience with microfluidics did not include optics. We developed a novel, millisecond micromixer based on bubble-induced, chaotic advection. My skills in microfluidics were then adapted to some optofludics work. We developed a tunable microlens based on diffusion of salutes to form a Liquid gradient refractive index (L-GRIN). This microlens has two degrees of freedom; a feat which to our knowledge has not been implemented by previous optofluidic microlenses. My latest completed project was the realization of an optofluidics, variable, optical attenuator which tunes the output power of an optical signal using a tunable, fluid interface. The mixing of two fluids alters the reflectivity of a tunable refractive interface. The device was fabricated by single-step, soft-lithography and used common, inexpensive materials. The result is an optical attenuator with a performance comparable with commercial devices which could be produced at a fraction of the cost by mass production based on soft-lithography. I have attained some initial results on optofluidic interferometer devices intended for on-chip monitoring of drug concentrations. I intend to extend my optofluidics platform by developing integrated optofluidic light sources and assisting my college on developing on-chip flow cytometry.
“Computational Simulations of Flow over The Surface of a Formed Thrombus”
by: George Long
Advisor: Keefe Manning
Abstract
Thrombosis and thromboembolization still remain a major impediment to the successful use of cardiovascular devices, such as ventricular assist devices, arterial stents, and artificial heart valves. Flow separation produced by these devices has been known to be one of the major contributors to these phenomena. In order to better understand the flow’s roles, a computational fluid dynamics (CFD) study was performed. First, an in vitro flow loop consisting of a backward-facing step was used to generate an experimentally formed thrombus. Its geometry was captured using magnetic resonance imaging, and CFD simulations were then performed with a reconstructed, computer rendering of the thrombus. Two-dimensional studies at an average Reynolds number of 525 and a sinusoidal velocity-inlet waveform were performed on the in vitro model’s geometry. Additionally, three-dimensional simulations using a physiologic velocity-inlet waveform taken from a human iliac artery were performed at an average Reynolds number of 1000, with and without the reconstructed thrombus, to observe the flow and surfaces stresses. Also, the frequency of the velocity-inlet waveforms was varied from 50 to 100 bpm to observe the effects of Strouhal number. From these simulations, wall shear stress magnitudes were shown to increase with Strouhal number, with the 100 bpm case producing values up to 50% higher than the 50 bpm case, approaching 35 dynes/cm2. Also, flow instabilities were more pronounced in the 100 bpm case compared to the lower frequency cases, with Taylor cells visible during periods of flow deceleration. From these results, predictions into the likelihood of thrombosis and embolization were made, with thrombosis being more likely in the 50 bpm case than the higher frequency cases, due to the larger recirculation regions observed past the step and reduced wall washing. While at the current flow conditions significant embolization is not likely to occur, at higher Reynolds numbers, the 100 bpm case is predicted to be more susceptible to embolization, due to an increase in wall shear along the clot’s surface, with shear stresses of 50 dyne/cm2 observed.
For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@engr.psu.edu