BRIDGING THE GAP TECH WAKE FOREST UNIVERSITY ENGINEERING, SCIENCE, School of Biomedical Engineering and Sciences & MEDICINE SBES NEWS S U M M E R / F A L L 2 0 0 8 • w w w . s b e s . v t . e d u SBES Is At The Forefront Of Regenerative Medicine What is Regenerative Medicine? from United Network for Organ Sharing, 4/29/08. The main thrust of regenerative medicine is to harness the The prevalence of obesity, hypertension and diabetes, and the natural healing process by helping cells to grow, divide and dif- growing numbers among the aging population will likely increase ferentiate outside of the body before implantation, or by stimulating the need for organs for years to come. Then there are the complica- progenitor cells to repair tissues in the body. tions of the actual transplant; rejections and medications. Immuno- Why Regenerative Medicine? suppressing medications become a lifelong need and carry both Since the first organ transplant in 1954, there have been few short and long-term side effects that can reduce the quality and life clinical advances. Organ transplantation was a major advance in span of patients. medicine in the twentieth century but demand for transplantable Where will the organs come from? organs consistently outstrips supply. Every Regenerative medicine can bypass the organ shortage and 11 minutes, a name is added to the the transplant complications by making the donor and the recipient national transplant wait- the same. A biopsy from the patient yields cells that are nurtured ing list, and more in the laboratory to form functional tissues and organs which can than 97,014 then be reimplanted into the patient. The use of a patient’s own people cur- cells eliminates the risk of rejection that accompanies traditional rently await organ transplantation so that immune system-altering drugs are not transplants. necessary. An aver- Wake Forest’s role in new technology commercialization age of 18 Children and teenagers, who have received laboratory grown people bladders using their own cells, have experienced success. Dr. die each Anthony Atala, at Wake Forest Institute for Regenerative Medicine day while (WFIRM), implanted the first laboratory-grown bladder in 1999, waiting for and in April 2006 released a report discussing the long-term results organs, of seven patients who had the surgery. Tengion is a regenerative according medicine company which is commercializing this technology and to statistics has already entered phase II clinical trials. Where discovery and hope meet In January 2007 scientists from the WFIRM and Harvard Medical School discovered a new source of stem cells and have used them to create muscle, bone, fat, blood vessel, nerve and liver cells in the laboratory. Atala and colleagues discovered a small amount of stem cells in the amniotic fluid — estimated at one percent — which can give rise to many of the specialized cell types found in the human body. These stem cells are called amniotic fluid-derived stem (AFS) cells, and it took seven years of work to determine if they were true stem cells. These cells were harvested from amniotic fluid taken during routine amniocentesis procedures and similar cells were isolated from the placenta or “afterbirth.” This breakthrough may provide alternative cells to those isolated from embryos. Functional tests of AFS cells transplanted into mice have been successful, such as injection of neural cells created from AFS into mice with degenerative brain disease. The cells grew and “re-populated” the diseased areas. Many scientists believe stem cells have the potential to replace damaged cells and tissue in conditions such as spinal cord injuries, diabetes, and Alzheimer’s. See Forefront, page 6

A tissue engineering scaffold made from liver is injected with a red dye. Cells are removed from the liver but the ul- trastructure of the extracellular matrix is left intact, so much so that the vascular network is visible as the dye travels through the vessels. This scaffold can be re-populated with cells and new tissue created with a built-in vascular supply. WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 2 www.sbes.vt.edu

LOOKING TO THE FUTURE Producing the Next Generation of Biomedical Engineers

he Virginia Tech – Wake Forest School of Biomedical Engineering our academic research program.” SBES has brought talented individuals/ and Sciences (SBES) strives to meet today’s technological and ac- researchers together, and we are seeing their work now as stepping- T ademic needs by preparing students to anticipate the future of the stones for future innovation. For example, in April 2008 successful clinical biomedical field. This unique school was established by bringing together trials were completed in irreversible electroporation (IRE), based on a the Wake Forest University School of Medicine, the Virginia Tech College paper published in 2005 by Rafael Davalos, Ph.D. IRE is a proven method of Engineering, and the Virginia – Maryland Regional College of Veteri- for tumor ablation that creates no secondary thermal effects and therefore nary Medicine, combining the resources and leveraging the strengths of preserves the extracellular matrix, microvasculature, and nerves. these founding members to produce an environment that fosters graduate The combination of a public university from Virginia with recognized education and outstanding interdisciplinary research. Each college is in- excellence in engineering and veterinary medicine and a private univer- ternationally recognized, and SBES combines researchers and resources sity in North Carolina with recognized excellence in human medicine has into a coherent group. resulted in a program that is much more than the sum of its parts. Re- According to Dean Richard Benson of the Virginia Tech College of cently the Global Human Body Modeling Consortium awarded the Center Engineering, “The creation of SBES — a dynamic and collegial depart- for Injury Biomechanics (CIB) $4.9 million, and the Wake Forest Institute ment that resides in three colleges at two universities — is the most for Regenerative Medicine (WFIRM), where many of our students and interesting academic partnership that I have witnessed in three decades faculty are involved in tissue engineering, has been awarded $42.5 mil- of university life. Our partnership with the Wake Forest University School lion from the U.S. Department of Defense as part of a joint consortium. of Medicine and the Virginia – Maryland Regional College of Veterinary I invite you to read about these and many other initiatives and success Medicine has brought tremendous opportunities for biomedical engineer- stories in this newsletter. I think you will agree with Dr. Wayne Meredith, ing research and education to the Virginia Tech College of Engineering.” director of the Division of Surgical Sciences at Wake Forest University The school has made significant achievements in academics, in re- School of Medicine, that “SBES is one of the most exciting and stimulat- search with increased funding, and in professional growth by securing bril- ing ventures of our schools. I am constantly amazed and inspired by liant faculty members who are leading us into the future. Ge Wang, Ph.D., the unique inquisitive environment it creates and the productivity of the is an excellent example. He is the Samuel Reynolds Pritchard Professor research that results.” It is with this attitude that we will continue to chart of Engineering, the director of the SBES Biomedical Imaging Division, our course. and a joint faculty member at Virginia Tech and Wake Forest. Among his ~ by Wally Grant, Ph.D., Head, Virginia Tech - Wake Forest University many honors and contributions, Dr. Wang and his collaborators published School of Biomedical Engineering and Sciences (SBES) the first papers on spiral cone-beam CT, biolumi- nescence tomography, Haiou Shen, Dr. Ge Wang’s and interior tomography, postdoctoral fellow, is prototyping each of which represents a state of the art optical molecular a frontier of biomedical tomography system. imaging. As I review the short-term success of SBES, I believe we are now strategically posi- tioned to be a leader in a unique academic program and to continue to de- velop as an internationally recognized educational and research biomedical engineering program. William Applegate, Ph.D., interim president of Wake Forest University Health Sciences and dean of the School of Medicine, states that “SBES is the “Jewel in the Crown” of VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences www.sbes.vt.edu 3 HEART FAILURE... Over 70 million people in the United the left ventricular filling hydrodynamics and students headed by Dr. Pavlos Vlachos have States with high blood pressure are at risk for diastolic heart failure. It will enable the devel- been investigating how the blood flow in simu- left ventricular diastolic dysfunction (LVDD), opment of novel and more reliable diagnostic lated coronary arteries changes after stent and numerous studies have shown a link be- tools. This work will be presented at the 2008 implantation based on the choice of design. tween LVDD and heart failure. However, due ASME Summer Bio- AEThER has begun to compensatory mechanisms, early stage engineering Confer- efforts to characterize dysfunction can be difficult to diagnose, and ence. Also, a portion the parameters which despite numerous advances in clinical modali- of this work will con- govern magnetic drug ties the prognosis and diagnosis of LVDD has tribute to Kelly Stew- targeting. remained unchanged over the past 20 years. art’s master’s thesis For additional The Advanced Experimental Thermo-Flu- and will be part of the information, please ids Engineering Research (AEThER) fluid me- Ph.D. dissertation for see www.me.vt.edu/ chanics laboratory at Virginia Tech, in conjunc- John Charonko. AEThER/index.html tion with a team of cardiologists headed by The AEThER Dr. William Little from Wake Forest University Laboratory is focus- Baptist Medical Center, has been investigat- ing on other health ing the role of hydrodynamics in LVDD. This issues such as, the Color M-Mode investigation involves the examination and hemodynamics of Echocardiogram analysis of clinical imaging of the left ventricle. commercial coronary processed region of Anonymous patient data was routinely di- stents and magnetic interest displays the agnosed by cardiologists and then sent to Vir- drug targeting. Using change in position ginia Tech for hydrodynamic analysis. Through a powerful laboratory-based measurement of the 50% isovelocity contour with respect a series of image processing techniques and technique called Digital Particle Image Ve- to time to calculate the propagation veloc- the implementation of fluid dynamics equa- locimetry (DPIV), a team of SBES graduate ity. tions, Color M-mode echocardiogram and phase contrast magnetic resonance images are being used to non-invasively collect propa- gation velocities and pressure distributions within the left ventricle. Propagation velocity is the wave speed at which the left ventricle is filling, as fluid moves towards the left ventricu- lar apex. Current results show an improved correlation of decreasing propagation velocity with decreasing diastolic function over cur- rently used clinical methods of calculating propagation velocities. The pressure gradi- ents and velocities calculated by the newly developed automated algorithms allow for the combination of variables to define dimension- less scaling parameters to characterize the effectiveness of the left ventricular filling. FOUR CHAMBER HEART IMAGING This research will augment the under- Instantaneous pressure distribution within the heart, superimposed on velocity vectors. standing of the causal relationship between Four chamber heart imaging was performed using MRI.

his research will augment the understanding of the causal relationship between the left ventricular filling hydrodynamics and diastolic heart failure. T It will enable the development of novel and more reliable diagnostic tools. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 4 www.sbes.vt.edu REDUCING BRAIN INJURIES Approximately 50,000 people die annu- University Center for Injury Biomechanics ship between kinetic input and resultant head ally from Traumatic Brain Injury (TBI) in the (CIB) has projects that cover the entire human injury in cause and effect terms, which will United States, representing more than 33 body, its research efforts in head injury biome- require an understanding of the relationship percent of all injury-related deaths (Centers for chanics provide a clear illustration of how to between the local response of the intracranial Disease Control and Prevention, 2002). The investigate human tolerance to impact loading contents and injury outcome. leading causes of TBI death are violence, mo- at the macro, meso, and micro levels of tissue The CIB is using a multi-phase research tor vehicle accidents, and falls. injury. plan to better understand and ultimately re- While the Virginia Tech – Wake Forest Research has yet to show the relation- duce brain injuries.

THE FACULTY

Dr. Warren Hardy, also of Vir- Dr. Clay Gabler’s and Dr. ginia Tech, examines brain displace- Warren Hardy’s teams at Virginia ment and deformation during impact Tech are examining traumatic brain using high-speed biplane x-ray, and injury (TBI) at the cellular level. neutral density targets (NDTs) im- The project is being conducted in planted in the brain. Relative motion, collaboration with Dr. Beverly Rzi- maximum principal strain, maximum galinski at the Edward Via Virginia shear strain, and intracranial pressure College of Osteopathic Medicine are measured in human cadaver head Brain shape scaling and the (VCOM, located near the Virginia The CIB head impact accelera- and neck specimens. This research SIMon brain injury model. Tech campus), and Dr. Warren tion measuring system used in has shown that during impact, local Hardy. TBI can occur from high- Virginia Tech football helmets. brain tissue tends to keep its position Dr. Joel Stitzel’s group is work- rate, high-magnitude mechanical and shape with respect to the inertial ing with the National Highway Traffic loads to the head from events such Dr. Stefan Duma, of Virginia frame, resulting in relative motion Safety Administration to develop geo- as car crashes or explosive blasts. Tech, leads a team whose focus between the brain and skull and metric shape and size scaling factors Their approach is to study the injury is to quantify the head accelera- deformation of the brain. A comple- for the pediatric brain and skull. The response of cell cultures of neural tions of football players and has mentary, multidisciplinary research goal is to generate size and shape cells to these mechanical loads developed a unique sensor that effort involves the study of diffuse appropriate finite element models of both through in-vitro experiments consists of 12 accelerometers and axonal injury (DAI) development after the human brain for injury prediction. and through computational model- a wireless transmitter designed head impact and the associated injury Kerry Danelson, a Ph.D. student, is ing. The group has developed an for integration into existing football cascades. This study is designed to working with Dr. Carol Geer, a neuro- Advanced Cell Deformation System helmets. The data are collected in obtain the direct relationship between surgeon and interventional radiologist, (ACDS), which can provide pulse real time and downloaded to the focal neuronal damage as determined and Dr. Dennis Slice, an anthropolo- durations ranging from 20 to 100 sideline computer during all prac- via classical pathology immunohis- gist from the University of Vienna. ms, independent control of strain tices and games. The Virginia Tech tochemistry techniques, and magnetic Danelson has digitized landmarks and strain rate, and arbitrary pres- football team helmets have been resonance imaging (MRI) using a por- from CT and MRI scans of normal pe- sure pulse shape. When combined instrumented with these sensors for cine in-vivo model. The tissue staining diatric brains and is using these land- with finite element models of these five seasons, and over 50,000 head is performed at the Virginia-Maryland marks with advanced shape analysis experiments, these systems should impacts have been recorded that Regional College of Veterinary Medi- techniques to assess size and shape lead to a fundamental understand- provide linear and rotational accel- cine, and the MRI scans are con- changes quantitatively in the brain ing of the complex biochemical eration traces for each hit. The data ducted using the Bruker 7T scanner with age. The scaling relationships will response of neural tissues to impact are being used to develop brain of the Wake Forest University Center allow the prediction of mild traumatic and blast loading. injury criteria to validate advanced for Biomolecular Imaging. This study brain injury in any age individual. In computational models of the human will quantify the location and extent the future, the team will be extending brain. of neuronal damage as it develops their work to the aged population and over time using spectral and diffusion- looking at the effects of shape chang- weighted MR scans. es on the injury metrics resulting from similar impacts for predicting clinically relevant injuries.

A typical cadaver specimen Healthy neurons before preparation showing the NDT impact (top), severely injured implants in two clusters of neurons after impact (bottom). seven targets. (Rzigalinski, Ellis, et al., unpublished data) VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences www.sbes.vt.edu 5

Center for Injury Biomechanics (CIB) Awarded $4.9 Million by the Global Human Body Models Consortium

In order to develop a unified The CIB’s success in obtain- computer model, eleven interna- ing these contracts speaks to the tional car manufacturers and sup- quality of the students and faculty pliers joined together and formed in the program. the Global Human Body Models Initially, four sizes of individ- Consortium, LLC (GHBMC). uals will be modeled to cover the Through a competitive pro- maximum range of normal sizes posal process from universities in the world population. A fifth throughout the world, the GHB- and 50th percentile female and MC selected the CIB as the over- a 50th and 95th percentile male all Integration Center, led by Dr. model will be developed. These Joel Stitzel and in collaboration models will match the industry with Hongik University in Korea. standard dummies in use today. The CIB was also selected The GHBMC effort began as the Center of Expertise (COE) June 2008 and involves an initial for the abdomen portion of the 3.5 year effort to develop the model, led by Dr. Warren Hardy, baseline models. The GHBMC in collaboration with the French will then, over the next 4-12 National Institute for Transporta- years, undertake the develop- The Hybrid III ATD (Left) has instrumentation to predict injuries in- TM tion and Safety Research (IN- ment of scalable models to repre- directly. Finite element models of the human such as the THUMS (Right) incorporate detailed anatomy for specific injury prediction. RETS). sent other shapes and sizes fol- lowed by models to represent children approach involves empirical and es during impact are needed, and and the elderly. numerical components at multiple will be obtained throughout the The Virginia scales. For the development of course of this project. Tech – Wake For- an improved finite element tool The CIB is conducting the est University Cen- for the evaluation of local abdom- majority of the empirical work, ter for Injury Bio- inal injury, material properties, and INRETS is conducting the mechanics will be tolerance of tissues and systems, majority of the numerical work for centrally involved and the local structural respons- the abdomen Center of Expertise. in this effort, along with numerous members of the School of Biomedi- cal Engineering CIB Facts and Sciences. esearchers at the Virginia Tech – Wake Forest University For the abdo- Center for Injury Biomechanics (CIB) strive to reduce fatali- men model, the ties and injuries as a result of traumatic impacts. The CIB CIB is collaborating R has over 40 researchers working on projects with applications in with Dr. Philippe automobile safety, sports biomechanics, military restraints and con- Beillas of INRETS in Lyon-Bron, sumer products. With over 15,000 sq. ft. of research space, the CIB and Dr. Philippe is equipped to perform everything from large scale sled crash tests Vezin, the head of to the smallest cellular biomechanics study. CIB research projects the Laboratory of are supported through research awards from the NIH, CDC, NSF, Initial abdominal modeling of the major Biomechanics and DOT, DOD as well as a range of industrial sponsors. Since its incep- abdominal vasculature and solid organs, Impact Mechanics tion in 2003, the CIB has been awarded over $25 million in research generated by INRETS using geometry from the (LBMC). funding. www.cib.vt.edu male Visible Human Project. The research VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 6 www.sbes.vt.edu

Crash Injury Research and Engineering Network (CIREN) The Crash Injury Research and Engineer- integral member of the team, along with Katie ing Network (CIREN) was established in 2006 Morgan, CIREN study coordinator and Kathryn with the goal of bringing engineering and med- Loftis, lead graduate student on the program. ical expertise together with experienced crash Students and faculty members work closely investigators to understand with their counterparts at the how injuries are caused in car CIB at Virginia Tech and with crashes. The Toyota – Wake the Center for Biomolecular Forest University School of Imaging at WFU, which assists Medicine CIREN center is one with detailed reconstructions of eight centers in the U.S. with of injuries. A CIREN case vehicle that was involved in funding and participation from In the past two and half a frontal impact with a tree. Toyota Motor North America years, the CIREN center has and the National Highway Traf- enrolled 100 cases with the investigating the injury mechanisms and injury fic Safety Administration. goal of determining the injury criteria associated with blunt liver trauma. CIREN brings together Injuries sustained by mechanism for each and ev- Her current projects focus on characterizing engineers and medical doctors CIREN patients in car ery serious injury sustained the tissue-level and organ-level mechanical from Wake Forest University crashes. Above: Rib by the occupant. Using this response of the liver under loading conditions and Virginia Tech to evalu- fractures from a side information and other data- that are representative of motor vehicle crash ate car crashes resulting in impact. Below: Posterior bases, NHTSA and automobile scenarios. Results of this research could be serious injuries. The study’s pelvis acetabular fracture manufacturers and suppliers used to enhance the design of the abdominal from a frontal impact. participants come to Wake For- use CIREN to develop better component of crash test dummies. In addi- est University Baptist Medical safety systems such as seat- tion, this research could be applied to develop Center’s Level I Trauma center belts and airbags for vehicles, finite element simulations of injury-producing by ambulance or helicopter and to improve vehicle crash- abdominal impact events. This line of research with injuries that are often worthiness. The CIREN center could lead to vehicle design improvements life-threatening. Dr. Wayne is also involved in understand- that will mitigate the risk of serious abdominal Meredith, Chief of Surgery at ing injuries in the elderly, soft injury in motor vehicle crashes. Wake Forest University Health and hard tissue injuries in the The ultimate goal of CIREN is to save Sciences (WFUHS), and Dr. chest and abdomen, and how lives and mitigate injuries received in car Joel Stitzel, a researcher in pregnant women are injured in crashes. The CIREN center is one of the the Center for Injury Biome- car crashes. prime examples of how the SBES and CIB col- chanics, are the PI’s of the CIREN center. CIREN has worked with numerous cases laboration and the partnership between SBES Michael Burke, a crash investigator with years involving liver lacerations and one of the CIB’s engineers and WFUHS physicians have had a of experience reconstructing crashes, is an researchers, Dr. Jessica Sparks, is actively real impact on saving lives.

FOREFRONT (Continued from page 1) Challenges to overcome advancements while seeking to harness our own body’s healing power. In spite of the great advances WFIRM has made in the regenera- The WFIRM, in partnership with McGowan Institute for Regenerative tive field, there are many hurdles left to overcome, such as: inability to Medicine, was awarded $42.5 million over five years to form a con- expand cells, inadequate vascularity, inadequate biomaterials/scaffolds, sortium called the Armed Forces Institute of Regenerative Medicine and inadequate psysiological and pharmacological function. (AFIRM). Its research focus will be battlefield injuries including burns, In working with the liver, the cells are painted on a scaffold, but wound healing without scarring, craniofacial reconstruction, limb recon- the problem is getting them to migrate and multiply. Dr. Mark Van Dyke, struction, regeneration or transplantation, and compartment syndrome. who leads the Biomaterials Program at WFIRM, compares the cell A second consortium will be managed by Rutgers and the growth difficulties of some cell types to a human trying to walk without Clinic. arms and legs. Components of regenerative medicine being considered Scientists at the WFIRM, led by Atala, have taken a creative ap- by engineers at WFIRM are controlled release of bioactive molecules, proach by focusing on inter-disciplinary teams of investigators. Scientists assessment of the mechanical properties of regenerative medicine prod- work freely with each other sharing all points of their work. By building ucts, the processing of novel biomaterials, and parameter optimization on the ideas of others, they are giving birth to new innovative ideas and of scaffolding materials that support cell growth and function. leading the field of regenerative medicine. As the students develop, they WFIRM has envisioned the future medical needs of a society are producing results, and when they leave they take with them a proven and the research is intended to encompass ever-changing technical approach to solving the problems of regenerative medicine. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences www.sbes.vt.edu 7

Quantitative Imaging Enhances Knowledge of Disease Drs. Robert Kraft and Craig Hamilton are reconstruction, and analysis of leading the quantitative imaging initiative at the the image data. Wake Forest campus. Their work is aimed at Illustrated on this page providing quantitative imaging tools to the user are three collaborative proj- community, encompassing numerous collab- ects involving Cardiology, the orative projects that benefit from quantitative Comprehensive Cancer Cen- imaging. ter, and Radiology. Traditionally, medical imaging has been Hamilton’s collabora- qualitative, that is, the intensity of a pixel is tion with cardiologist Greg arbitrary and only conveys relative information Hundley, M.D. and radiologist when comparing pixels. In contrast, the pixel Jeff Carr, M.D, (both SBES intensities in quantitative images are directly affiliate faculty), is part of the proportional to a physical parameter (tempera- Jackson Heart Study which ture, density, blood flow, velocity, concentra- is investigating the causes of tion, etc.). cardiovascular disease (CVD) Quantitative imaging is of great interest in African-Americans and de- because it provides repeatable, observer- veloping strategies to prevent These images show a quantitative cerebral blood map non- independent measures of physical quantities. or reduce the burden of both invasively measured with Pulsed Arterial Spin Labeling MRI. However, it is technically challenging and preclinical and clinical CVD Pixels represent actual flow in units of milliliters of blood requires careful attention to the acquisition, in the future. An important per 100 grams of tissue per minute. Images such as these can provide important information for diagnosis of various marker of car- diseases and conditions. diovascular abnormality image acquisition software for the scanner as is vascular stiffness, shown at well as the post-processing software required left, which is evaluated using to produce temperature maps and time-tem- quantitative tools developed perature curves, shown below. by Hamilton. Kraft has been developing advanced Kraft and Hamilton are techniques for measuring cerebral blood flow collaborating with a large using perfusion MRI for several years and has team led by Frank Torti, M.D., recently begun providing clinicians with the director of the Comprehensive ability to acquire quantitative perfusion maps Cancer Center, and M. Nichole (shown above) as part of the clinical offering Rylander, Ph.D. Virginia Tech at Wake Forest. This capability is finding wide SBES, in a novel approach application in a number of studies of cerebral aimed at laser ablation of can- disorders. cer tumors. Careful monitoring of temperature is important as part of the treatment, and is provided by quantitative temperature maps pro- Using phase contrast MRI, we can measure the aortic pulse duced using In the upper left is a qualitative axial anatomical image of a wave velocity. Top left is a qualitative anatomic image through the 7 Telsa mouse with an implanted tumor in the hind right flank. Below the aortic arch. Top right, the pixels represent a quantitative this image, we show a quantitative temperature map acquired animal MRI velocity map of blood flow in mm/sec. At the bottom, the time using MRI during interstitial laser hyperthermia therapy. Using delay for the propagation of the blood’s pulse wave from the scanner. They this type of imaging, temperature versus time from a region ascending aorta (red) to the descending aorta (green) provides are develop- of interest within the tumor for three different interstitial laser an important clinical measure of arterial stiffness. ing both the hyperthermia treatments can be plotted. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 8 www.sbes.vt.edu

Dr. M. Nichole Rylander (back) helping SBES student Jessica Fisher.

SBES Explores Advanced Methods for Cancer Therapy, Detection, and Imaging

he National Cancer Institute es- needed for all forms of cancer. Faculty from cer treatment. Integrating nanoparticles Ttimates over 1.4 million new cases the School of Biomedical Engineering and into laser therapy can enhance thermal of cancer will be diagnosed and over Sciences (SBES) in collaboration with Wake deposition and selective tumor destruc- 550,000 deaths from cancer occurred Forest University Comprehensive Cancer tion. Rylander’s lab focuses on measur- in the United States alone in 2007. Center are developing advanced methods ing and modeling the tissue response to Cancer treatment presently, remains for cancer therapy utilizing nanotechnology, nanoparticle-mediated laser therapies. based primarily on treatment approaches microfluidics, electroporation, laser optics, She is specifically exploring the use of developed over a quarter-century ago. heat/mass transfer, computational model- multi-walled carbon nanotubes (MWNT) Non-specific and highly toxic chemother- ing, and tissue engineering. which function as an antenna when apy treatment, aggressive radiation ther- Dr. M. Nichole Rylander’s research excited by infrared radiation causing en- apy, and invasive surgical resection are in nanomaterials has the potential to offer hanced tumor cell kill through increased a patient’s primary means of recourse exceptional imaging and treatment solu- temperature elevation. against this deadly disease. Conse- tions since they present a new toolset with Dr. Chris Rylander’s Biotransport quently, cancer patients today battle both a unique size range closely matching that and Optics Laboratory is investigating the disease and the cure. Inadequacies of cells (1 to 1,000 nm), a substantial mul- tissue optical clearing which has the po- in the ability to administer therapeutic tifunctional capability, and an inherently tential to improve optical diagnostic and moieties to selectively reach the desired large surface-to-volume ratio. Rylander’s therapeutic procedures. In laser-based targets with marginal or no collateral Nanotherapeutics and Bioheat Transfer therapeutics, successful treatment out- damage has largely accounted for this Laboratory is exploring the use of a variety come may depend on a desired tempera- discrepancy. Alternative, more effective of nanoparticles (nanotubes, nanoshells, ture increase in selected tissue regions imaging and treatment protocols are nanohorns) for improved imaging and can- Continued on next page VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences www.sbes.vt.edu 9

Continued from previous page nently destabilize the use, or diseases resulting in cell membranes of such as cancer, destruction the targeted tissue are a serious prob- of targeted thereby killing the lem. tissue, cells. Biomedical while Davalos’ re- engineering of- maintain- search has showed fers exciting new ing tem- the complete regres- options to repair perature sion in 12 out of and replace these Microtubes and Nanofiber structures. below the Photograph of in vivo human 13 treated tumors damaged tissues, damage skin during application of in vivo using IRE on a type of aggressive as well as study their mechanics in or- threshold the TOCD (above). Ex vivo sarcoma implanted in mice.IRE is a proven der to prevent future injury. Freeman’s in non- porcine skin demonstrates technique to destroy targeted tissue with Musculoskeletal Tissue Regeneration increased light transmission targeted sub-millimeter resolution. Furthermore, the (MTR) Laboratory seeks to produce when the specimen is trans- tissue re- illuminated with visible light procedure can be monitored in real-time new therapies and techniques for tis- gions. subsequent to application using ultrasound, and spares nerves and sue replacement, regeneration, and the Tis- TODC (below). blood vessels, enabling treatment in other- study of tissue mechanics.Freeman’s lab sue optical wise inoperable areas. creates nanoscaled synthetic grafts for clearing Davalos received an Early Career musculoskeletal tissues such as bone, is a tech- Translational Research Award from the cartilage, and skeletal muscle. The con- nique that Wallace H. Coulter Foundation to pursue structed grafts are designed to withstand could sig- this research. This program provides fund- the loads experienced by natural tis- nificantly ing for assistant professors in established sues. Electrospinning is used to create improve biomedical engineering departments within nanofibers of various polymers. His lab is the ca- North America. able to control nanofiber orientation and pabilities Davalos’ Bioelectromechanical Sys- direction, in order to fabricate specialized of laser- tems Lab is also developing Cellular Micro- structures such as microtubes and “core- based hyperthermia therapy of cancer systems to aid in cancer cell detection and shell” nanofibers (with one polymer on by permitting delivery of light deeper into treatment. The current focus the outside and another on tissue, while sparing healthy tissue above is to develop implantable the inside). the tumor. Positive preliminary results micro-devices to detect the M.N. Rylander and demonstrating effectiveness of me- presence of circulating tumor Freeman are also col- chanical Tissue Optical Clearing Devices cells (CTCs) in post-operative laborating with Paul (TOCD) using white light photography, cancer patients. Oftentimes Gatenholm of the Materials infrared imaging radiometry, and opti- treated cancer patients suffer Science and Engineering cal coherence tomography have been from recurrence or even me- department and SBES, and obtained in Rylander’s research group. tastasis after their treatment. researchers at Wake Forest IRE completely destroys TOCD prototypes laterally displace inter- During early stages of tumor University, Mark Van Dyke unwanted tissue within 48hrs stitial water and blood, inducing zones of growth, there is a low con- via necrotic cell death. A: (SBES) at the Institute of dehydration, reducing tissue thickness, centration of cancer cells that untreated control tumors; B, Regenerative Medicine and and modifying optical properties. Optical exfoliate into bodily fluids. C: 2 hours and 6 hours after Darren Seals in Cancer penetration depth may increase on the They hypothesize that detect- IRE, D: 48 hours complete Biology, to develop a novel tumor necrosis. order of two-fold. ing the presence of CTCs in vessel-tissue-bioreactor Dr. Rafael Davalos’ Bioelectrome- post-operative patients can be an indication bioreactor system for gaining insight chanical Systems Laboratory is develop- of cancer recurrence and an active implant- into vessel and tissue interaction in a ing methods to detect and treat cancer able device to monitor patients and destroy tumorgenic state. It is anticipated that this using microfluidics and biotechnology. such cells would stifle the spreading of the system will be used to study cancer de- Davalos co-invented a new method to disease and potentially cure patients. velopment, tumor growth, and tumor vas- treat tumors known as irreversible elec- Dr. Joseph Freeman’s Musculoskel- cularization in a wide variety of tissues. troporation (IRE). The procedure involves etal Tissue Regeneration (MTR) Laboratory Better understanding of the mechanisms placing electrodes near the targeted is focused on developing engineered tis- of tumor vessel and tissue proliferation region to deliver a series of low energy, sues to replace damaged or diseased tis- and their response to various drug agents microsecond electric pulses for approxi- sue associated with cancer. Damaged mus- will also permit identification of new can- mately one minute. These pulses perma- culoskeletal tissues, through trauma, daily cer therapeutic targets. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 10 www.sbes.vt.edu SBES Collaboration Creates an Engineered Bone Graft Dr. Aaron Goldstein, at Virginia Tech of mechanotransduction – the mechanism process by which shear stress – induced – in collaboration with Dr Brian Love at the by which mechanical stimuli affect cell be- by fluid flow – stimulates the deposition University of Michigan, Dr Jeff Hollinger at havior (e.g., gene expression, formation of of a bone-like extracellular matrix. Recent Carnegie Mellon University, and Dr Scott bone tissue) – and perfusion culture of adult results show that fluid flow activates a cas- Guelcher at Vanderbilt University – has stem cells in porous scaffolds. cade of molecular signaling events, includ- been developing methods to form engi- One biomaterial project is the incor- ing the activation of transcription factors, neered tissue by combining adult stem poration of amorphous calcium phosphate that stimulate expression of various growth cells, a resorbable biomaterial scaffold, and (ACP) into conventional biomaterial scaf- factors. a perfusion bioreactor. folds. ACP is a bioactive ceramic similar to The theory is that growth factors ac- The scaffold serves as a carrier and hydroxyapatite, but because of the absence cumulate in the extracellular environment, support structure for delivering cells and of crystallinity, it dissolves readily in aque- where they can guide tissue formation. To bioactive factors, and perfusion bioreactor ous environments and raises the local cal- probe the temporal patterns of gene induc- is being used to condition the adult stem cium and phosphate concentrations. These tion by mechanical stimulation, Sharp has cells and induce them to secrete growth ions can reprecipitate in and around tissues incorporated a reporter gene into the cells; factors that will accelerate healing in the to facilitate osteoblast differentiation and the those cells that are expressing the gene patient. formation of new bone tissue. of interest will give off light (color image at Goldstein has three main research Kate Laflin, an undergraduate, and left). thrusts. They are the synthesis of novel Jenni Popp, a Ph.D. candidate, are incorpo- In order to integrate porous biomaterial biomaterial scaffolds, molecular analysis rating ACP into degradable poly(lactic-co- scaffolds and mechanical stimulation, the glycolic acid) (PLGA) Goldstein laboratory has developed a perfu- scaffolds (black and sion bioreactor culture system. white image at left). The ongoing work of Kate Kavlock, a The resultant materi- Ph.D. candidate, has shown that perfusion als may then either stimulates synthesis of a bone-like extracel- be implanted directly lular matrix by adult stem cells. However, into bone tissue de- the objective is not to form a bone-like tis- fects, or combined sue within the bioreactor. Rather, it is to use with adult stem cells the bioreactor to stimulate the adult stem prior to implantation. cells to express growth and differentiation At left, an SEM image of a sintered PLGA microsphere scaffold. Lindsay Sharp, factors, that – when implanted into a bone The small particles are zirconia-stabilized ACP. At right, cells another Ph.D. candi- defect – will direct infiltration of a capillary expressing target gene give off light. date, is probing the network and initiate new bone formation.

Freeman and Laurencin Develop Novel Tissue Scaffold Dr. Joseph Freeman of fiber braiding and twisting in the growth of new tissue. student Lee Wright, show that the MTR Laboratory at Vir- order to mimic the mechanics Both mechanical studies changes in scaffold behavior ginia Tech and Dr. Cato Lau- (elastic and and mathe- can be directly attributed to rencin, Chair of Orthopaedic viscoelastic matical model- due to changes in braiding Surgery and head of the Cen- properties) ing have been and twisting angle. ter for Musculoskeletal Re- of the natural used to char- This provides the ability generation and Repair at the ACL. This acterize these to alter the mechanics of the , have scaffold is de- scaffolds. The scaffold to match the proper- developed a novel tissue en- signed to be- modeling of ties of various tissues. Cell gineered scaffold based on have like a nat- the viscoelas- studies have shown that this a braid-twist method of con- ural ligament tic behavior, scaffold does support the struction for anterior cruciate while providing ACL fibroblasts growing performed growth of ligament fibroblasts ligament (ACL) replacement. a biodegrad- an extracellular matrix on a by Freeman and the production of new The scaffold combines able matrix for scaffold. and graduate extracellular matrix. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences www.sbes.vt.edu 11

Dr. Freeman works with SBES student Tea Andric.

SBES Professor Shares His Research with Students from His Hometown

r. Joseph Freeman, head of the science,” explains Freeman. Each disc is a five-to-seven minute televi- DMusculoskeletal Tissue Regeneration (MTR) He decided to share his research with sion show with musical introduction. On the Laboratory at Virginia Tech, understands the students from the Newark school system. disc Freeman and one of his students explain power of positive examples in the lives of Freeman and the students from his an aspect of their work. school-age children. laboratory have recorded DVDs describing It was enjoyable for the lab and the re- Until the age of 10, Freeman lived in the work that they do for students from third sponse from the students has been great. Mrs. Newark, N.J., a city that has struggled with to eighth grade. These DVDs are then sent to Freeman has shown the video to her class poverty, crime, unemployment, and at one teachers in the Newark, N.J. school system, and to students from her school’s afterschool point a 50% dropout rate of high school stu- Mrs. Diana Freeman of Alexander Street program. She describes the video as an asset dents by ninth grade. School, and Mrs. Heather Jones of Maple to her science classes, saying, “My students Currently, Newark, N.J. is listed in the Avenue School. Along with being science understood many of your concepts because top-ten cities with the highest poverty rate teachers, they are also Freeman’s mother and you not only explained it in simple terms, but (24%) by the Catholic Campaign for Human sister, respectively. illustrated your explanations.” Development. “I had the idea for this program after at- Now that the DVDs have achieved a “I was blessed because my parents tending my mother’s classes during Career small measure of success, Freeman wants to understood the power and importance of an Day a year ago. The students were very do more. He is arranging to have a web con- education. As college graduates, they served excited about what I did and asked a lot of ference with the students during Career Day as educational role models for me, but not questions. I wanted to keep their enthusiasm events. everyone is fortunate enough to have that. As for math and science going but there was no Freeman is also looking to expand the a product of Newark, with family members that way that I could visit New Jersey on a regular program to schools in Virginia. He would also still live and work there, I wanted to do some- basis, so I thought about sending a DVD,” like to speak at local schools to raise the inter- thing to get children excited about math and Freeman says. est of children in math and science. VIRGINIA TECH WAKE FOREST UNIVERSITY School of Biomedical Engineering and Sciences 12 www.sbes.vt.edu Educational Opportunities with SBES…

The Virginia Tech — the mentorship of physicians and Wake Forest University other medical personnel. School of Biomedical While many possibilities Engineering and Sci- exist, one scenario is that under ences sponsors a clinical the mentorship of a physician, rotation for engineering the student completes a pre-en- students in the Ph.D. counter assignment, attends pro- program. Its purpose is cedures, goes on rounds, meets to provide engineering with the physician to discuss the students with real ex- procedures and related engineer- R otation perience in the medical ing issues, and completes post- arena in order to better encounter assignments. The na- understand how their ture of involvement beyond this is SBES students Matt Rittler, Bradley biomedical research at the physician’s discretion. Fol- Davidson, and Xi Li participating in the projects relate to clinical lowing the rotation completion, Gross Anatomy session of Clinical Rotation. practice. students can meet with the physi-

SBES C linical The rotation con- cian to discuss their assignments, tion is an opportunity for students Forest University Baptist Medical sists of four weeks during experience, and other issues of to develop real-world context for Center in Winston Salem, and which the students take interest to the mentor. their studies and research, a key opportunities exist at the VA-MD part in gross anatomy, The key is that students can component to a successful career Regional College of Veterinary patient simulation, and bring as much to the process as as a biomedical engineer. Medicine located on the Blacks- clinical situations under the physician. The Clinical Rota- Rotations are held at Wake burg campus.

Virginia Tech is one ate students with a quantitative physiology. Every summer, 15 McNair Scholars program and the of 13 universities chosen and integrated bioengineering/ students from across the country Multicultural Academic Opportuni- to participate in a new di- bioinformatics related educational participate in didactic coursework ties Program (MAOP). rected venture to promote and research experiences. The and workshops in each of the For the second summer, bioengineering and bioin- program is also designed to mo- thrust areas taught by SBES or the BBSI program will be bring- formatics related careers tivate these students to pursue VBI faculty experts and conduct a ing students from nine different and graduate education. graduate degrees and careers in research project under the guid- universities to Virginia Tech to Participating are Virginia biomedical engineering and bioin- ance of a faculty mentor. live, learn, work and play. Each Tech-Wake Forest School formatics related fields. In addition, professional student will be working in his/her of Biomedical Engineering BBSI emphasizes three development activities, such as mentor’s lab but will get an over- and Sciences (SBES) and major thrust areas: computational team building and presentation view of the other research areas the Virginia Bioinformatics systems biology, computational skills, are integrated into the 10 in SBES and VBI through classes Institute (VBI). bio-imaging and computational week summer experience. and workshops. The Bioengineering The final end-of- Planned summer activities & Bioinformatics Sum- summer research sympo- include site visits to the Wake mer Institute (BBSI) is a sium allows the students Forest Institute for Regenerative nationwide effort funded the opportunity to present Medicine, the Wake Forest Uni- by the National Science their research in the form of versity Comprehensive Cancer Foundation (NSF) and oral and poster presenta- Center and Tengion. the National Institute of tions to other Virginia Tech Students are not the only Biomedical Imaging and student summer research ones who benefit from this pro- Bioengineering (NIBIB) of programs, including the gram as SBES and VBI faculty the National Institutes of will offer opportunities to collabo- Health (NIH). SBES student Tea Andric rate and develop future research (left) working with Abasha As a collaborative projects. Virginia Tech hopes Lewis, 2008 BBSI student effort between SBES and in Dr. Joseph Freeman’s the rising juniors and seniors will VBI, the BBSI program lab perform tensile tests on choose Virginia Tech for their

Su mmer I nstit u te (BBSI) B ioengineering & ioinformatics provides undergradu- a scaffold. graduate education. VIRGINIA TECH WAKE FOREST UNIVERSITY Biomedical Engineering and Sciences www.sbes.vt.edu 13

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Despite Challenges, Tanaka Pursues Dreams

Determination is a key characteristic in to do with Martin for the remainder of the se- on these migratory cells. Current mathematical describing Martin Tanaka, a husband and the mester?” He decided to offer Martin a project methods are generally based on processes father of four boys. After a 12-year break from on brain tumors, specifically gliomas, which that are relevant to the main tumor body and academics, Martin came back to Virginia Tech are highly invasive with a poor prognosis, de- not migrating cells.After reviewing the litera- to earn his Ph.D. in biomedical engineering. spite medical intervention. ture on mathematical modeling, Martin pro- Martin left Virginia Tech in 1993 with an M.S. Since he was still working on his biome- posed a new hybrid model that includes both and joined industry. Seizing an opportunity chanics research and writing his dissertation, deterministic and stochastic methods, which to relocate to Blacksburg, Martin pursued his Martin found this a challenge not only to his Puri calls “quite innovative.” His hybrid model dream. Martin’s wife, Dana, returned to work expertise area, but also to his time. Puri be- takes a deterministic approach for the inside while he left his job to concentrate on his stud- lieves a key strength of the SBES program is of the tumor and uses a stochastic method ies. in producing students who thrive in an inter- for its outside migrating cells, while looking at Challenges abounded due to the time disciplinary environment. Martin turned to Dr. cell populations and their spatial distributions. between his master’s degree and his entry Pete Santago, SBES Associate Head at the Although Martin’s hybrid model will still require into the SBES doctoral program. While taking Wake Forest campus, for suggestions regard- supportive clinical and experimental data, a mammalian physiology class, Martin real- ing a co-advisor for the oncology expertise he this could be a major advance in modeling for ized the last biology class he had taken was would have to acquire. Martin said that “due to gliomas or others cancerous tumors that might in high school in 1984. He faced similar chal- the SBES program, connections and resourc- also rapidly metastasize. lenges throughout the program. For instance, es were readily available, and Wake was very Martin allotted his time between the Matlab, a popular computer program used for responsive and supportive.” Dr. Waldemar glioma project and defending his biomechan- mathematical modeling, had to be mastered Debinski, director of the Brain Tumor Center ics dissertation. A recent SBES graduate, while he was taking courses. FORTRAN, the of Excellence at Wake Forest Medical Center, Martin will focus on his biomechanics work programming language, had become obsolete. agreed to help with the project. at Wake Forest, but has been so intrigued by There are numerous tracks to choose Gliomas are often not diagnosed until the glioma project that he plans to continue in the SBES program, some of which include they become large and begin to affect brain working on it in his spare time. Puri will also other departments. Martin followed the biome- and bodily functions. These tumors could be continue with the project. He and Tanaka have chanics track. He was advised by one of the described as having long hair-like projections submitted a research paper for publication. top five researchers in the country for move- from a main tumor body. These projections of Martin Tanaka recalled Kevin Granata’s advice ment dynamics in cerebral palsy, Dr. Kevin migratory cells are the culprits that invade un- as he pursued his . Dr. Tanaka was Granata, a professor in the Department of affected healthy brain tissue and can’t be sur- definitely “thinking big” on this project due to Engineering Science and Mechanics (ESM). gically removed. Martin focused his research Granata’s influence. One reason Martin chose Granata as an advi- sor was his understanding and support for students who had a family life. Granata always SBES is an affiliate with the Institute for Critical Technology and Applied Science (ICTAS) at Virginia said, “Think big, and don’t try to do something Tech. ICTAS supports and promotes cutting-edge research at the intersection of engineering, science incrementally better than the other person; be and medicine. The partnership between SBES and ICTAS was forged due to the dynamic nature of risky and make a significant contribution.” Mar- visionary research shared by both organizations. Working with ICTAS enables SBES to utilize emerg- tin has taken Granata’s advice to heart. ing technologies. As a result of aligning with ICTAS, SBES research will advance through the use of its Martin learned that the class that Gra- premier laboratories and facilities. In October 2008, SBES will join with ICTAS in a new nata had recommended for Fall ’07, taught by 100,000-square-feet building. For more information please see: Dr. Ishwar Puri, ESM Department Head was http://www.ictas.vt.edu canceled due to the aftermath of the April 16th tragedy at Virginia Tech when Granata was killed. Martin asked Puri about the possibility of taking the course as an independent study. Puri readily agreed. The course consisted of a weekly meeting and an on-line lecture. Ac- cording to Puri, “Martin took this very serious- ly.” He completed the work in half a semester. This led Puri to a perplexing question, “What VIRGINIA TECH WAKE FOREST UNIVERSITY Biomedical Engineering and Sciences 14 www.sbes.vt.edu

S T U D E N T P R O F I L E S

“Moving Ahead”

Saami Yazdani came to Virginia Tech to those truly friendly and kind people that you campus, and they began working on arterial pursue biomechanics in the Engineering Sci- enjoy knowing. Dr. Joel Berry, his Ph.D. advi- stents. This led him to take full advantage of ence & Mechanics (ESM) Department. A self- sor, agrees and is amazed at the people ‘Yaz” the Virginia Tech – Wake Forest SBES pro- declared “late bloomer,” it wasn’t until his fourth knows, everyone from the custodians to the gram and he chose to work at the Wake Forest year as an undergraduate that everything surgeons. campus. clicked. Now you could use the words “flourish- “Yaz represents the kind of graduate for Yaz believes “the SBES program has the ing” to describe him. which SBES was intended to produce, a true best of both worlds, where you get to work in In 2006, he co-authored a manuscript that biomedical engineer,” Berry says. engineering and a clinical setting.” pointed to his future direction in research. “En- Upon completion of his undergraduate In the first year of the SBES program at gineering of Blood Vessels from Acellular Col- degree, Yaz continued with his master’s in Wake Forest, Yaz and Berry performed finite lagen Matrices Coated with Human Endothelial ESM with Dr. Demetri Telionis, working in the element modeling of arteries and stented ar- Cells.” In 2007, with Dr. George Christ, Wake fluid mechanics laboratory. His focus was on teries, reviewing computer modeling stress in Forest Institute for Regenerative Medicine fluid dynamics and pulsatile flow in tubes (rep- the artery wall and relating it to stent design (WFIRM) and SBES faculty, Yazdani co-au- licating arteries) and stented tubes (replicating and mechanical properties. During this time, thored a chapter entitled, “Tissue Engineering stented arteries). they began performing research with Dr. Shay of Large Diameter Vessels” in Principles of Yaz states, “It’s basic engineering; if blood Soker at the WFIRM, which has a close affili- Regenerative Medicine. flows through it, it excites me!” ation with SBES. Together, they began with Yazdani is affectionately known as “Yaz” During this time he met Dr. Joel Berry, a developing bioreactors for tissue engineered to his many friends. member of the Virginia Tech – Wake Forest arteries; by his second year, Yaz was asked to Karen Watson, administrative assistant School of Biomedical Engineering and Sci- work at WFIRM. at Wake Forest, describes “Yaz” as one of ences (SBES) faculty from the Wake Forest Yaz gained beneficial knowledge concern- ing the cells of blood vessels from Soker and continued the development of bioreactors to improve engineered blood vessels. This led Yaz from tubes and computer modeling to actually developing new methods for growing cells and seeding tissue engineered arteries. Working with Dr. Randolph Geary and Bryan Tilman, vascular surgeons at Wake Forest University School of Medicine and Dr. James Yoo from the WFIRM, the research was taken from the laboratory to animal implant testing, enabling them to study installed bioen- gineered arteries preliminary to human use. As Yaz leaves as a 2008 Ph.D. graduate in biomedical engineering, he will take the next steps of progression in truly understanding the complete cardiovascular system. Joining CV Path Institute in Maryland, a non-profit organization, he will be a research scientist working with Dr. Renu Virmani, regard- ed as the world’s expert in vascular pathology. Expounding on his artery research, he will now be able to study the effects of the stent in the human body. In particular, he will investi- Saami Yazdani (left) and Dr. Shay Soker are shown with the vascular bioreactor, which gate the pathological remodeling of arteries to preconditions and prepares the graft by inducing mechanical forces that mimic the native stress and strain associated with stents and arterial system prior to implantation. other devices. VIRGINIA TECH WAKE FOREST UNIVERSITY Biomedical Engineering and Sciences www.sbes.vt.edu 15

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“Pilot Group” Graduate Makes Significant Mark in the SBES Story

Matt Rittler was a member of the first was fairly easy. He had considerable strength coming students small group of students to enter the School in physiology and cell and tissue knowledge. as preparation of Biomedical Engineering and Sciences pro- His research is in angiogenesis -- the for the mamma- gram when it began in 2003. behavior of vascular endothelial growth factor lian class. His Matt came to Virginia Tech with a double (VEGF) which binds to receptor sites on cell outstanding per- B.S. degree in biochemistry and exercise surfaces to stimulate blood vessel growth. formance and physiology from McDaniel College where he Over-expression of VEGF has been linked to solid depend- graduated summa cum laude, and was in- several pathological conditions including the ability led to yet ducted into Phi Beta Kappa and the Beta Beta vascularization of cancer tumors. Of special another chance Beta Biological Honor Society. interest is a secreted form of one receptor to assist. A Maryland Distinguished Scholar, he which can compete with VEGF for “binding Matt Rittler In the Fall began work in 2000 on an M.S. degree in space” and thus inhibit angiogenesis. If blood of 2006, Rittler human nutrition, foods, and exercise. His pro- vessel growth in cancer tumors can be inhib- and another SBES graduate student teamed gram focus was in biochemistry but even then ited, the cancer can hopefully be defeated. to run a new Internship program called the biomedical engineering was the field he really Matt’s research involves building math- Bioengineering and Bioinformatics Summer In- wanted. He completed his Ph.D. in biomedical ematical models of how this binding and stitute (BBSI), a collaboration between SBES engineering in 2008. inhibition occurs, so that the mechanisms of and the Virginia Bioinformatics Institute de- While in HNFE he met Dr. William Huckle the process can be predicted, tested, and ma- signed to offer summer research opportunities in the VA-MD Regional College of Veterinary nipulated to an advantage. The ultimate goal to rising juniors and seniors. Medicine who became his advisor. He applied is to simulate experiments computationally Matt inherited the program completely for the Ph.D. in veterinary medical sciences for that couldn’t otherwise be done in a laboratory in January 2007 and continued developing it, Fall 2002 (pre-SBES). setting. serving as its coordinator through the summer Talk of the formation of SBES had al- Beyond the degree pursuit of 2007 and into the Fall. In October of 2007, ready begun earlier that year, and while it Beyond his academics, Matt made sig- he was sent to the BMES conference in Hol- didn’t exist yet, Matt knew he wanted to be nificant contributions to SBES. When it was lywood to give a platform presentation about part of the new program which was expected decided that mammalian physiology would be the BBSI program. to begin admitting students in the Fall of 2003. a requirement for the new program’s degree, During his time here, Matt also contrib- SBES was officially approved by SCHEV Matt was asked if he would be the graduate uted greatly to the SBES recruiting effort. He in March of 2003, and the following fall Matt assistant for the course due to his extensive was always a faithful student volunteer during entered the SBES program as one of the origi- anatomy/physiology background. the spring College of Engineering Graduate nal “pilot class” of students. He says, “They weren’t exactly sure what Recruiting Weekend. He also represented Even though his background was not in that would mean in the beginning or what [I] SBES at outside events such as the College of engineering, the idea of biomedical engineer- would do.” But as things developed, weekly Engineering Career Fair at N.C. State. ing was very appealing to him. review sessions were created to be part of the Dr. Wally Grant was once heard to joke, “Biomedical engineering sounded sexy,” course which Matt would run. “What can we do to prevent Matt from gradu- says Matt with a smile. He liked the idea that it The first year was a challenge. There was ating?” was so interdisciplinary and multi-directional; no video-broadcast setup for his sessions so Matt’s immediate future is in the Wash- that it could open so many doors. he met with the few Virginia Tech students in a ington area where he will take a post-doc He explains that he initially experienced a Norris classroom, and “did the best he could” position in the National Cancer Institute, a little discomfort feeling like an “outsider” (refer- helping the Wake Forest students by e-mail. sub-division of NIH, where he will work again ring to his attachment to the Vet School). Engi- He ran the recitations for three years in angiogenesis. neering was a bit like a “clique” in high school and was also asked to be a co-instructor for Eventually, he says, he imagines himself – a club he wasn’t in. “I knew I’d just have to the BMVS 4064 Intro to Medical Physiology gravitating back to the academic world. He get over it,” he says. course when it was created. loves teaching and thinks he’d like to blend it The big issue for him was his math defi- In Fall 2005 he created and taught a with doing research in a university setting. cit, and once he’d caught up on that, the rest short-course in anatomy to the new SBES in- ~ by T. Sentelle VIRGINIA TECH WAKE FOREST UNIVERSITY Biomedical Engineering and Sciences

www.sbes.vt.edu

Virginia Tech does not discriminate against employees, students, or applicants on the basis S B E S F A C U L T Y H O N O R S / A W A R D S of race, color, sex, sexual Dr. Y.W. Lee orientation, disability, Dr. Rafael V. Davalos Assistant Professor Assistant Professor age, veteran status, • NASA Tech Briefs “2007: The Year in Technology” • November 2007: Excellent Presentation Award, Ko- national origin, religion, Listed Irreversible Electroporation as a top break- rean Nutrition Society International Conference or political affiliation. through of 2007. Dr. Mark Paul Anyone having questions • 2008 Early Career Translational Research Award in concerning discrimination Assistant Professor, Biomedical Engineering from the Wallace H. Coulter • NSF Career Award, Spatiotemporal Chaos in Fluid or accessibility should Foundation contact the Office for Equal Convection: New Physical Insights From Numerics Dr. Stefan Duma Opportunity, 540/231-7500. Dr. M. Nichole Rylander Professor, Mechanical Engineering Assistant Professor • Best Paper, 2007 Association for the Advancement of • Recipient of the 2008 Outstanding New Assistant Automotive Medicine Professor Award Dr. Joseph Freeman Dr. Pavlos P. Vlachos SBES News Assistant Professor Assistant Professor, Mechanical Engineering courtesy of the Institute • 2008 Early Career Translational Research Award in • NSF Career Award, Arterial Flow Dynamics Effects of for Critical Technology Biomedical Engineering from the Wallace H. Coulter Pusatility, Compliance, and Curvature Foundation and Applied Science Dr. Ge Wang (ICTAS) Dr. H. Clay Gabler Virginia Tech & Wake Forest University Faculty Associate Professor • Feature article in Radiological Society of North Amer- • 2007 Ralph H. Isbrandt Automotive Safety Engineer- SBES is bridging the gap ica, November 2007, reporting the pioneering work ing Award on bioluminescence tomography between engineering, • 2008 Lloyd L. Withrow Distinguished Speaker Award science, and medicine • Fellow of the International Society for Optical Engi- Dr. Warren Hardy neering (effective 1/1/2007 for specific achievements Wally Grant, Ph.D. Associate Professor, Mechanical Engineering in bioluminescence tomography and x-ray computed Head • Best Paper, 2007 Stapp Car Crash Journal tomography

Pete Santago, Ph.D. Associate Head S B E S S T U D E N T A C H I E V E M E N T S / A W A R D S

Pamela Stiff Scott Gayzik Instrumentation Conference, April 4-6, 2008, Copper Editor • First Place, Best Student Paper Award, Stapp Car Mt., Colorado Crash Journal 2007 Scott Gayzik, Kerry Danelson, and Amber Bonivtch David Simpkins Greg Webster • First Place, Enhanced Safety of Vehicles 2nd In- Designer • John D. States Best Student Paper Award, Associa- ternational Collegiate Student Safety Technology Design Competition, Enhanced Safety of Vehicles Please send comments tion of Advancement of Automotive Medicine, 2007 in Melbourne, Australia Conference, 2007 and address corrections to Pamela Stiff, Jill Bisplinghoff, Steven Rowson, Doug Gabauer, Amber Bonivtch Kerry Danelson, F. Scott Gayzik, Sarah Manoo- • American Society for Bone and Mineral Research [email protected] gian, and Andrew Kemper Sun Valley Workshop on Skeletal Tissue Biology, • Won eight of 12 awards at the Biomedical Sciences Alice L. Jee Memorial Young Investigator Award Re- cipient: 2008

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