The increasing integration of engineering in the health sciences promises a revolution in new technologies that will help save lives. Drexel University's activity in biotechnology builds upon Philadelphia's prominence in medical technology and pharmaceutical strengths. The Center for Advanced Biomaterials and Tissue Engineering provides a focal point of expertise and research in tissue engineering, an emerging, multidisciplinary field committed to the development of biological substitutes to regenerate, restore, maintain and/or improve tissue function. Drexel University also leads an NSF CRCD grant whose goals are to train students broadly in teaching and mentorship activities, while developing new curricula in biomedical engineering related research. Research activities in these areas are expected to grow significantly as a result of the merger between Drexel University and the Medical College of Pennsylvania-Hahnemann University, which is the largest private medical school in the United States.
1) Engineering Biomimetic Interfacial Drug Delivery Systems - (Dr. Anthony Lowman – Whitaker Young Investigator)
In this project, teachers will be exposed to cutting edge research techniques in the area of tissue engineering and drug delivery.
The "state of the art" in medical implants are devices that can communicate with the body through chemical or electrical signals. Devices such as biosensors and long-term drug delivery implants must be able to rapidly exchange solutes in order to be effective. However, the body naturally encapsulates implanted devices in a dense fibrous tissue that prevents efficient exchange of chemical solutes. In order for these implant strategies to be realized, a tissue-implant interface that allows chemical communication between the implant and surrounding tissue and vasculature is needed. For this reason, the main objective of this work is to synthesize water swellable polymers, known as hydrogels, into cellularly-invasive macroporous coatings, and evaluate the ability of these coatings to support a viable microvasculature using in-vitro analysis techniques.
This work includes two main sections, a polymer materials characterization section and a cellular interaction and characterization section. The polymer materials will be characterized with the role of a tissue scaffold in mind. Properties that are important to tissue scaffolds, such as material modulus, porosity, pore size, and water content, will be evaluated. Mercury porosimetry, scanning electron microscopy (SEM), compression testing, and swelling studies will be employed to obtain this information. Figure 13 is a SEM obtained during one such a set of experiments. It depicts a hydrogel with an average pore size of 10-20 µm, which would be large enough for the ingrowth of a microvasculature.
Cellular experiments using human microvascular endothelial cells adult dermal (HMVEC-ad) will be carried out under controlled proangiogenic conditions. Immunofluorescent antibody staining will be utilized to visualize the depth of penetration, differentiation (tube formation), and the density of tubules. Figure 14 shows the growth of HMVEC-as into a collagen matrix (Matrigel®) which will be the control in these experiments. These features will then be compared to the network characteristics obtained in the polymer characterization section to determine the effects of hydrogel scaffold properties upon the formation of a microvasculature.
2) Biofluid Mechanics: Flow Visualization for Teachers, Students, and Doctors (Dr. David Wootton)
Fluid mechanics is one of the primary factors influencing thrombosis, the formation of an undesirable blood clot within a blood vessel. Thrombosis causes artificial prosthetic blood vessels to clog and fail, and small clot particles that are dislodged by flow (thromboemboli) cause stroke and kidney failure in artificial heart patients. Dr. Wootton’s lab studies the relationships between blood flow conditions and thrombosis. Prothrombotic flow conditions include abnormal shear stress, long cell residence time, and complex flow.
To develop an appreciation for fluid mechanics and its applications to biomedical technology, teachers will participate in research on the flow patterns that promote thrombosis in the dialysis access graft, an
artificial blood vessel that is crucial for sustaining life in patients with kidney failure. Using (1) video dye tracing in lab models, and (2) computational fluid dynamics software (Figure 15), the teachers will create flow visualizations that illustrate the shape, location, and dynamics of these features. Teachers will help the lab by creating images that clearly illustrate high-risk flow patterns for non-engineers, such as doctors, dialysis nurses, vascular technicians, and high school students.
Web-accessible images and movie clips, created by the teachers, will be posted to allow high-school students to view these images as part of a science module on flow in biology and medicine. Teachers may also develop hands-on or visual demonstrations of flow features and flow quantities.
3) Biological Colloids- (Dr. Steve Wrenn - Whitaker Young Investigator)
The primary focus of this component in technological education of the teacher workforce in the Philadelphia school district is to create an awareness of the role of cholesterol precipitation in human disease.
Coronary artery disease will continue to be the leading cause of morbidity and death in the next century, both in men and women, and in developing and developed nations alike. Fourteen million people in the United States have coronary artery disease, and of these one million develop an acute coronary event, and 400,000 die, each year. Although less morbid, gallstone disease afflicts 12% of the adult US population, and annual medical expenses relating to gallstones exceed $2 billion. Although several non-surgical treatments remove stones temporarily, the only permanent cure for gallstone disease is surgical removal of the gallbladder. The number of laparoscopic cholecystectomies (i.e., the operation to remove the gallbladder) performed each year exceeds 500,000.
The common link between these two widespread diseases is precipitation of cholesterol crystals from bodily fluids, owing to the extremely low solubility (i.e., 10-8 M) of cholesterol in water. The dependence of disease on the cholesterol crystallization (nucleation) rate is encouraging, for it suggests the possibility that controlling the cholesterol nucleation rate can prevent the diseases. Turning this possibility into a reality first requires a detailed understanding of the cholesterol nucleation mechanisms within the contexts of gallstone formation and heart disease. Research is underway in the Biological Colloids Laboratory at Drexel University to elucidate the cholesterol nucleation mechanism using a combination of fluorescence and light scattering techniques.
To achieve the goal of developing web-based high school instruction material, teachers will work with Dr. Steven Wrenn in the Biological Colloids Laboratory to study cholesterol precipitation in artificial bile- and blood-based systems. After conducting this research, the teachers will work with Dr. Wrenn to develop an instruction set, replete with photographs and data graphs, to share the experience with their high school students. The class materials developed by the teachers through this effort will provide unique insights to high school physics and chemistry students who would not otherwise have access to these computational tools.
