The REU program focuses on research in the major thrust areas of the Department of Biomedical Engineering. Examples of research projects that are designed for the 10-week REU program are listed below.
Biomaterials, Tissue Engineering, and Drug Delivery
Cardiovascular Biomaterials and Vascular Engineering: Roger Marchant is a Professor in Biomedical Engineering. His research is concerned with biomimetic materials and vascular tissue engineering. Cell and molecular studies of the underlying mechanisms provide the basis for developing novel biomimetic materials and blood compatible interfaces. This research has a foundation in macromolecular engineering, which is combined in understanding lessons from Nature, to design and engineer biomaterials derived from principles of self-assembly and biological hierarchical structure.
Biomimetic interface materials: This project area involves the design and synthesis of biomimetic polymers directed towards improving the blood compatibility and tissue engineering artificial blood vessels. The projects are based on the hypothesis that controlled spatial placement of oligosaccharides and/or cell adhesion peptides on a biomaterial will facilitate programmed biological responses that minimize non-specific interactions, and enhance selective cell interactions. Students may focus on the biomimetic design, synthesis, and analysis of the self-assembling materials using spectroscopic techniques and AFM with in vitro evaluations of blood compatibility using microscopy techniques, or on the tissue engineering aspects, by focusing on protein and endothelial cell interactions with the materials, which involves cell culture studies.
Vascular tissue engineering: This project, in collaboration with Dr. von Recum, seeks to address the challenge area of regenerative medicine for bioengineering vascular networks in engineered tissues. The overall goal is to create a prevascularlized tissue bed by tuning a cellular platform to enhance homing and remodeling, and a polymeric platform that is conducive for vasculogenesis. The research involves studies on stem cell derived endothelial cells and biodegradable extracellular matrix- mimetic hydrogel scaffolds.
Drug Delivery Platforms: Horst von Recum is an Assistant Professor is Biomedical Engineering. His research includes: Novel platforms for affinity-based drug and gene delivery; directed stem cell differentiation; and pre-vascularized polymer scaffolds for tissue engineering.
Affinity-Based Drug Delivery: In this project, the student will examine the how small molecule drugs incorporated into an affinity-based drug delivery platform will have a slower, more linear, and more therapeutically relevant release rate than diffusion based systems. Applications range from antibiotics to chemotherapy agents to HIV microbicides. The student will explore synthesis of a tunable drug delivery polymer, evaluate drug release, and therapeutic efficacy. Previous work by an REU student resulted in a manuscript.
Tissue engineering blood vessels: In this project, the student will examine the differentiation of stem cells, both embryonic and hematopoietic to become the various components of blood vessels. Stem cells show great promise as tissue engineering tools both in their unlimited replication potential and plasticity. Stem cells can be differentiated into circulating endothelial precursors, which facilitate repair and regeneration of large vascular defects. The student will investigate the use of novel stimuli-responsive polymers designed to allow binding and loading under one condition, and release or expression under another condition. We will examine the use of these polymers as scaffolds for engineered vascular tissue, and as selection substrates in the identification of novel angiogenic factors.
Orthopedic Tissue Engineering: Eben Alsberg is an Assistant Professor of Biomedical Engineering. His research primarily involves orthopedic tissue engineering, and drug delivery for functional tissue regeneration and cancer therapy.
Bone tissue engineering: The student project will address the hypothesis that in tissue engineering bone, regulating cell-biomaterial interactions, controlling polymer degradation, and delivering soluble osteogenic signals may modulate cellular behavior towards tissue regeneration. The specific experiments will involve transplantation of isolated cells on a biodegradable delivery vehicle, to create a functional biological replacement tissue without permanent remnants of foreign constituents; and the development of innovative methods to present specific signals to control cell behavior and subsequent tissue formation to guide the process of tissue regeneration. Through temporal and spatial presentation of soluble bioactive factors, mechanical forces, and biomaterial physical/biochemical properties, we will aspire to create microenvironments that regulate cell gene expression and new tissue formation.
Nanoscale Orthopedic Biomaterials
Steve Eppell is an Associate Professor in Biomedical Engineering. His research involves nanoscale self-assembly and structure-function relationships in connective tissues. A parallel research thrust involves technique development for probing biological systems at the nanoscale.
Mechanical properties of mineralized collagen gels: The student will learn how to make synthetic collagen fibrils starting with collagen monomers, and to then mineralize the fibrils. They will then learn how to uniaxially press the mineralized gel and dehydrate the material using a cold press. The student may also attempt to improve the mechanical properties of collagen gels by orienting the fibrils and crosslinking them to achieve a biomimetic construct. The degree of crosslinking will be determined using IR spectroscopy; while fibril morphology will be assayed using polarization light microscopy and Scanning Electron Microscopy (SEM), with changes in mechanical properties assayed using a dynamic mechanical analyzer.
Computer simulation of collagen fibril self-assembly: The student will use Matlab to create a model of a collagen molecule and compute the interaction energy between two molecules as a function of the relative displacement and angle between the two molecules. The student will build an interaction profile based on Coulombic interactions, van der Waals interactions, and an effective medium theory to handle hydrophobic interactions. The project draws on topics of electrostatics, solvation forces, programming in Matlab, and protein structure.
Calibration of near field nanoscale electrostatic measurements: This project focuses on developing atomic force spectroscopy so that electrostatic fields around nanoscale objects can be measured. The student will use current protocols to measure the electrostatic field around 50 nm diameter polystyrene spheres. This will involve learning some organic chemistry, how to image a sample by AFM, how to use a 100 MHz digitizing board to collect high bandwidth AFM data, and some computer programming skills to assist in data analysis.
Development of multifunctional nanoparticles for targeted drug delivery
Anirban Sen Gupta is an Assitant Professor of Biomedical Engineering. His research focuses on nanoparticle platforms carrying therapeutic and diagnostic payload, and surface-modified by cell-selective ligands are an effective way to achieve site-targeted delivery and release of bioactive agents to various pathologic sites while avoiding non-specific uptake and systemic side effects. The Integrative Nanomedicine Engineering and Technology (INET) laboratory lead by Dr. Sen Gupta uses this approach for developing targeted drug delivery platforms for vascular and cancer pathologies. The research involves synthesis and characterization of novel polymers, development of nanoparticles therefrom, surface-modification of nanoparticles with disease-specific 'homing' ligands, formulation of drugs in the nanoparticle, and study of cell-targeting and drug delivery using microscopy techniques.
Cancer-Targeted Drug Delivery: Efstathios Karathanasis is an Assistant Professor in Biomedical Engineering. Dr. Karathanasis' research focuses on an interdisciplinary approach to cancer diagnostics and nanotherapeutics. Specifically, his lab focuses on the development of imaging probes and methodologies for MRI and CT based on the integration of nanotechnology and drug delivery with anatomical, functional and molecular imaging to provide clinically-relevant prognostic and diagnostic tools as enablers for personalized cancer therapies.
Nanoprobes for molecular imaging of markers related to anticancer therapies: In this project, the student will be involved in the preparation and analysis of new nanoparticle-based contrast agents using synthetic tools (e.g. bioconjugate chemistry) and materials characterization (e.g. TEM, dynamic light scattering), followed by lipid-based nanoparticle fabrication (e.g. extrusion, thin film hydration) to prepare the agents. Subsequently the agents will be tested in cell cultures to evaluate the agents’ ability to specifically target receptors over expressed in tumors. Finally the particles will be used in rat tumor models to predict and monitor the therapeutic progress of chemotherapy and antiangiogenic treatments by imaging blood vessel function (e.g. flow rate, vessel wall permeability) and specific markers (e.g. VEGF-A and its receptor). Undergraduate students have carried out similar studies successfully.
Image-guided Drug Delivery: Agata Exner is Assistant Professor of Radiology and Biomedical Engineering. The major thrust of her research is to utilize discoveries at the exciting interface of drug delivery, nanotechnology and biomedical imaging to advance the field of cancer therapy. Currently, two projects under image-guided therapeutics are suitable for REU students: 1) we are developing an in situ-forming system for image-guided delivery of drugs to solid tumors. Specifically, we are investigating the use of ultrasound for noninvasive characterization and modulation of drug delivery from these implants, and assessing their efficacy in vivo as a standalone system and as an adjuvant to image-guided ablation. We hope to develop a platform technology for delivery of various agents, from small molecules to proteins. This research will advance the field of on-demand drug release from implantable devices and increase benefits of local drug therapy by enhancing drug retention and distribution. 2) We are creating targeted delivery vehicles for a thermosensitizing agent, which increases the susceptibility of cancer cells to heat-related injury. Here, we are evaluating a bioactive polymer as a thermosensitizer specific to cancer cells and developing a carrier vehicle for delivery and monitoring of this therapy with ultrasound. This research will broaden the impact of sensitizing molecules in cancer therapy and establish new approach to strengthen the use of hyperthermia in cancer treatment.
Targeted MRI Contrast Agents: Zheng-Rong Lu is a Professor of Biomedical Engineering. His research involves the development of novel targeted MRI constrast agents for the imaging of cancer and vascular diseases, as well as novel delivery systems for therpeutic SiRNA. Student projects for REU students include development of MRI contrast agents and the development of multifunctional SiRNA delivery systems.
Computational and Experimental Mechanobiology: Melissa Knothe Tate is a Joint Professor of Biomedical Engineering and Mechanical and Aerospace Engineering. She studies the effects of forces on cells and cellular structures, and transport at different length scales from tissue to cells. Two areas are suitable for REU projects are:
Cytoskeletal conformation in health and disease: The student will apply established protocols to investigate the conformation of the osteocyte skeleton in health and disease. Changes in the cytoskeleton, in response to the application of dilatational (e.g. compressive) and deviatoric (e.g. shear) stresses, will be investigated to determine the potential role of the cytoskeleton in adapting to dynamic mechanical and physiological environments. This project incorporates fundamentals of cellular mechanics with those of cell biology, empowering the student to apply state of the art methods in a multidisciplinary fashion.
Network modeling of biotransport in brains and bones: The project provides the student with the opportunity to apply computational modeling algorithms to understand transport of endogenous (e.g. nutrients and cytokines) and exogenous (e.g. drugs) transport through a student defined system, organ or tissue. These methods are being implemented to study transport through brain and bone tissue in healthy and pathological states. Designed for the student with mathematical or computational flair, this project affords the opportunity to apply theoretical techniques to patient care scenarios.
Engineering approaches for neural protection and regeneration in the CNS: Erin Lavik is an Associate Professor of Biomedical Engineering. Dr. Lavik investigates polymer, drug delivery, and tissue engineering approaches to preserving tissue and promoting repair in the central nervous system following injury or disease.
Materials to promote engineering a 3D model of the retina: In collaboration with ophthalmologists, we have identified a key set of retinal cells that are able to form synapses and communicate. By creating three dimensional poly (ethylene glycol)-poly-L-lysine gels with the appropriate mechanical properties, we are able to promote the migration and organization of these cells into normal retinal structures allowing us to investigate both the impact of drugs on these structures as well as the role of genetically altered cells in forming critical synapses.
Development of controlled release systems for neural regeneration: A number of drugs have been shown to promote regeneration, but they must be delivered locally over a long time scale. We investigate the formulation parameters that lead to sustained delivery of these drugs from injectable systems, test them in vitro to determine bioactivity, and then determine their effects in vivo in a simple nerve crush injury model.
Biomedical Sensing and Imaging
Electrochemical and Optical Biosensors
Miklos Gratzl is an Associate Professor of Biomedical Engineering. Dr. Gratzl is interested in cost-effective diagnostic devices, measurements of cellular neurotransmitter and cancer cell drug resistance.
BioMEMS platform for acute cellular transport and communication: The student project will involve developing a BioMEMS platform for neurotransmitter monitoring at PC12 cells and at cells derived from the nervous system, and testing different aspects of the approach. Examples include: oxygen metabolism at macrophages; simultaneous monitoring of oxygen and nitric oxide at macrophages; chloride and bicarbonate transport at cystic fibrosis related cell patterns before and after genetic treatment; and dopamine release at single PC12 cells. The student will gain experience with MEMS technology and wet laboratory practice, and experience with optical and electrochemical instrumentation, The student will develop skills for designing electronic circuits, experiments involving live cell preparations, write and implement software to control instruments, and analyze data with statistical methodologies.
Biomedical Image Analysis
David Wilson is a Professor Biomedical Engineering. Dr. Wilson’s research concerns biomedical image analysis including image registration, image segmentation, and image measurements. Application areas include interventional MRI and vascular MRI and in vivo cellular and molecular imaging.
Vascular image analysis (VIA): In this project, the student will be involved in developing the VIA computer program for visualization and image analysis of human blood vessel disease. MR images will be displayed with or without registration, noise reduction filtering, and coil sensitivity correction. Window-level values will be changed and stored so as to enable identical displays for multiple operators in a tissue analysis study. Tissue will be manually typed from multiple MR images using an interface where multiple, registered, images are visible side-by-side. A cursor will be linked to all images so that one can compare the MR signal for different morphological features. Various measurements will be exported into a spreadsheet, with data saved in an open format such that all the parameters can be easily identified. VIA will enable comparisons of the image analysis results. Expert versus expert comparisons of contours and tissue typing will be possible with statistical analysis. We will compare contours and tissue typing results imported from computer algorithms with those from experts. Visual comparisons will be possible, including comparisons to typed, registered histology images.
In vivo assessment of pneumonia using bioluminescent imaging: This project concerns assessing bacterial pneumonia infection non-invasively. The REU student will label bacteria with luciferase and use bioluminescent imaging techniques. The idea is to compare wild type and knockout mice, which have been modified to omit a protein thought to be important for neutrophil adhesion and movement. Serial in vivo studies will greatly aid the analysis. We will compare results from mice knockouts and wild types to see if there is a tendency for spreading of infection. The student also will participate in the imaging experiments and develop an image analysis method.
Biophotonics, Optical Biomedical Imaging, Optical Coherence Tomography. Andrew Rollins is an Associate Professor of Biomedical Engineering. He is interested in the application of advanced optics and photonics technologies for imaging and characterization of biological samples, and early disease and monitoring of therapy. Optical coherence tomography (OCT) is the primary basis of this research. Imaging scanners for clinical OCT: This project will involve the REU student in the design and construction of a compact optical scanning probe for clinical imaging. The experiments will include optical design; probe fabrication, and integration with clinical OCT instrumentation. Clinical applications include oral cancer, cervical cancer and bladder cancer.
Quantitative image analysis: This project will involve analysis of 2D, 3D and 4D OCT image sets using sophisticated commercial software (Amira), as well as development of original image processing algorithms (MATLAB). Tasks will include image rendering and visualization, segmentation, image feature extraction and tissue classification. Applications include early cancer detection, diagnosis of cardiovascular disease, and discovery of the structure and function of the early developing heart.
Cardiac Magnetic Resonance Imaging and Spectroscopy: Xin Yu is an Associate Professor of Biomedical Engineering. Dr. Xu's research is devoted to the development of state-of-the-art magnetic resonance imaging (MRI) and spectroscopy (MRS) technology for the integrative understanding of the heart under normal and diseased conditions. A variety of engineering approaches, including MRI/MRS technology, signal processing and software development, finite element analysis, and mathematical modeling, are employed for quantitative delineation of structure-function and energy-function relationships. The multidisciplinary approach provides a unique framework to apply engineering principles to life science applications.
Characterization of cardiac metabolomics: MRS has the potential for in vivo evaluation of cardiac metabolism under various pathophysiological states. Of interest is the information that can be obtained with phosphorus-31 (31P) and carbon-13 (13C) MRS. An REU student will be involved in the development of an integrative approach for comprehensive and mechanistic investigation of metabolic regulation in heart by combining experimental MRS with other experimental methods and mathematical modeling of tissue metabolism.
Delineation of cardiac structure with diffusion tensor MRI: The 3D organization of myocardial fibers is a critical determinant of cardiac biomechanics. This area focuses on developing MRI methods for quantification of 3D water diffusion tensor in the heart. Dr. Yu's lab has developed MRI methods for the analysis of diffusion tensor MRI (DTI) data that involves 1) calculation of diffusion tensor; 2) determination of fiber orientation by calculating the Eigen values and eigenvectors of the diffusion tensor; and 3) histological correlation by image coregistration and analysis with histological images. Students will be engaged in research that applies DTI to delineate microscopic changes in myocardial structure in diseased heart.
Neural Engineering and Rehabilitation
Neural Engineering: Dominique Durand is a Professor of Biomedical Engineering. He works in the new area of neural engineering, which is at the interface between engineering and neuroscience, and combines computational neuroscience, engineering and electrophysiology to solve problems in the central nervous system and peripheral nervous system (neural Interfacing).
Neural Interfacing: In the peripheral nervous system, nerve electrodes are being developed capable of stimulating and recording neuronal activity selectively. This methodology is applied to the hypoglossal nerve to restore potency in the airways of patients with obstructive sleep apnea and to design neural prostheses for patients with spinal cord injury and stroke. An REU student will be involved in computer simulations of both neurons and volume conductors that are used in conjunction with the experiments for the quantitative analysis of neural systems, and to design new electrodes for interfacing with the nervous system. In the CNS, the mechanisms of synchronization of neuronal activity during epilepsy are investigated using invitro brain slice preparations, in-vivo multiple electrode recording, computer models and clinical trials. The interaction between applied currents and neuronal tissue are studied to determine the feasibility of controlling seizures in patients with epilepsy.
Prosthesis for Coordinated Arm and Hand Function
Robert Kirsch is a Professor of Biomedical Engineering. Dr. Kirsch is interested in restoring arm and hand movement function to individuals with paralysis arising from spinal cord injury and other neurological conditions through the use of neuroprostheses based on functional electrical stimulation. The research tools employed include musculoskeletal biomechanical measurements, mathematical modeling and simulation, and tests of control concepts with neuroprostheses users. REU Students will have opportunities to learn how to measure human motor performance using state-of-the-art 3D video systems and 3D force measurement transducers. They will also learn how to record muscle activity and witness the involvement of biomedical engineers in the rehabilitation environment.
Command source evaluation for arm-hand neuroprosthesis: Functional electrical stimulation can produce muscle contractions that generate desired movements, but an interface through which the user instructs the system on what movement is desired must be developed. Students will investigate different possible command sources such as eye movements, head movements, voice commands, and EEG signals using a robotic simulation of a paralyzed arm. Different signal processing techniques will be employed and information transfer will be computed to evaluate each command source.
Model-based development of FES controller algorithms: Musculoskeletal modeling is a technique that uses mathematical descriptions of the skeleton, the joints, and the muscles to create a “virtual arm“ or a “virtual leg“ that can be used to perform simulations of movements of interest. The musculoskeletal model can be used as a proxy for an actual human subject, allowing simulations to replace tedious and perhaps risky procedures in the early evaluation of a new neuroprosthesis. Students will take anatomical measurements obtained from the literature, from experimental measurements, and from MR images, to obtain accurate measurements of model parameters. The model will then be used to develop feedback controllers for the arm and the leg that could be implemented in actual human subjects to restore function.
Motor Function Restoration with Neural Prostheses, Control of Orthotic and Prosthetic Systems
Hunter Peckham is a Professor of Biomedical Engineering. Dr. Peckham is interested in development of special sensor mechanisms for the detection of physiological events.
Development of sensor systems for detection of physiological events: Restoration of functional control of the paralyzed nervous system with neuroprostheses requires the analysis in real time of physiological events, such as foot to floor contact, or grasp force to sense contact pressure. The development of sensor systems that detect such events enables testing in clinical subjects the control algorithms to be used in more complex and clinically acceptable implanted systems. Furthermore, these sensor systems employ technologies that will be used in more complex implantable devices.
Analysis of command control techniques for neuroprostheses: The interface between the disabled person and the neuroprosthesis is one of the most complex challenges in the development of neuroprostheses. An effective command control interface requires that the control be natural and unobtrusive. Several alternative command control interfaces with a range of complexity are under development, including physical sensing of joint position, myoelectric activity, and cortical signals. Undergraduate projects in this area are to identify signal source and signal processing techniques to provide a command signal with the characteristics that enable an effective interface to the neuroprosthesis.
Neural Interfacing and Neural Prostheses: Dustin Tyler is an Associate Professor of Biomedical Engineering. Dr. Tyler works in the areas of neural interfacing and neural prostheses. The neural interface presents many significant challenges in the development of advanced devices designed to restore function in neurologically impaired patients. His research activities include peripheral nerve electrodes for upper and lower extremity neural prostheses; and the development of cortical electrodes, particularly for examining novel materials and methods of insertion for maximal integration with cortical tissue. Dr. Tyler’s neural prostheses interests are in stimulation of the larynx. The larynx is an intricate and complicated organ responsible for many functions, ranging from protection of the airway to production of voice. Dr. Tyler’s research activities include a neural prosthesis for prevention of aspiration in post-stroke patients; and neural prostheses for production of voice. The lab’s fundamental research tools include animal experimentation, clinical studies, histology and immuno-histochemistry, and computer modeling and simulation.
Neural Engineering, Neural Prostheses & Sensory Neurophysiology for Organ Function: Ken Gustafson is an Assistant Professor of Biomedical Engineering. His research interests focus on understanding the systems-level neurophysiology and neural control of pelvic functions, and using this information to design and develop neural prostheses that interface with native spinal neural circuitry and restore physiologic function. Lower urinary tract dysfunction can have a devastating clinical impact. His efforts include developmental and pre-clinical studies to translate research advances into clinical implementation. High frequency waveforms can be used to completely block nerve fibers. This technology can be applied to stop unwanted muscle spasms, improve organ function or stop pain. We are conducting in vivo experiments and in vitro analysis of electrode designs for implantation in humans. REU students will work with a team of graduate students, engineers, nurses, and physicians, to design, fabricate and test electrodes for implantation in humans. Students will learn the basics of neural stimulation and electrode materials. Students will have opportunities to observe surgical procedures, be exposed to commercialization activities and cadaver evaluations may result from a successful project. Also, understanding human neuroanatomy is critical in developing effective neural stimulation strategies.