Though specific research projects have not been finalized, the information below will give you an idea of the types of projects offered. Click on a project title to learn more.
Project 1. In vitro models of neuroblastoma using porous silk scaffold structural supports (Advisor: Jeannine Coburn, Biomedical Engineering). Neuroblastoma is the most common extracranial, solid tumor in the pediatric population accounting for 13% of all childhood cancer related deaths. Engineered in vitro cancer models are useful tools for understanding disease progression and developing new treatment approaches. To this end, we are engineering silk scaffolded NB models to create in vitro tumor microenvironments. The specific change to the silk scaffolds the students may evaluate include scaffold stiffness via change silk concentration or processing conditions, scaffold biochemistry by incorporating extracellular matrix molecules (type VI collagen, neurocan), and inclusion of fibroblasts into the culture environment. (return to top)
Project 2. Mechanobiology of heart valve disease (Advisor: Kristen Billiar, Biomedical Engineering). Heart valve diseases necessitate surgical replacement of over 300,000 valves per year as there are no pharmaceutical treatments or early warning markers, and the current mechanical and bioprosthetic valves have serious limitations of clotting or degradation. Tissue engineered heart valves are promising alternatives, yet our understanding of how the extreme hemodynamic environment of the valve affects host cell population and subsequent growth and remodeling of the valve scaffolds is limited. The Billiar lab develops and utilizes in vitro model systems to study the specific and combined effects of stretch, shear, fluid flow, stiffness, and cell-cell forces on valve cells. Potential project areas include effect of stretch on cell phenotype and migration, effect of fluid shear stress on attachment and cell invasion, and effect of stiffness and shear on endothelial-mesenchymal transformation. (return to top)
Project 3. Design and study of collagen-tethered LL37 for chronic wound healing applications (Advisor: Terri Camesano, Chemical Engineering). Natural antimicrobial peptides (AMPs), such as human-derived LL37, are among the most promising alternative antimicrobials due to their broad-spectrum antimicrobial activity, low likelihood of resistance and unique immunomodulatory and wound healing activities. The clinical application of AMPs has been hampered due to concerns about cytotoxicity, low in vivo stability, and a narrow therapeutic window. We are focusing on tethering, or attaching AMPs onto surfaces, as a strategy of delivering bioactive AMPs to surfaces while reducing cytotoxicity and improving stability. The REU participants will work alongside graduate researchers as part of a team, whose overall goal is to seeks to develop collagen tethering as a viable strategy to deliver broadly antimicrobial, non-cytotoxic, and stable AMPs to chronic wounds. We developed new chimeric versions of human LL37 with collagen binding domains (CBD-LL37) for tethering onto collagen-based wound dressing scaffolds, for the stable, non-cytotoxic delivery to chronic wounds. We created two CBD-LL37 peptides, with CBDs derived from collagenase (cCBD-LL37) and fibronectin (fCBD LL37). The REU participants will engage in experiments to evaluate the bioactivities, collagen-binding abilities, and biophysical mechanisms of cCBD-LL37 and fCBD-LL37 for their use in collagen scaffolds. Experimental techniques used for the characterization include quartz crystal microbalance with dissipation monitoring (QCM-D), which helps develop the mechanism of peptide-collagen interactions, along with atomic force microscopy (AFM), useful for the direct visualization of the collagen layers and/or the peptide-collagen interaction. (return to top)
Project 4. Role of shear and stretch forces on pulmonary endothelial glycocalyx (Advisor: Solomon Mensah, Biomedical Engineering). Pulmonary endothelial dysfunction plays a significant role in lung injury through changes in barrier permeability and edema. The goal of this project is to understand the effect of shear and stretch forces on human lung microvascular endothelial cells. This will be achieved by developing an in vitro system that will introduce a combination of shear and stretch forces to human lung microvascular endothelial cells. The effect of both shear and stretch forces on the endothelial glycocalyx will be evaluated with immunostaining and confocal microscopy and quantified using the NIH software ImageJ. Potential project areas include development of an in vitro flow setup to introduce mechanical forces to human lung microvascular endothelial cells, development of an artificial cytokine storm to determine its effect on the endothelial glycocalyx, and development of an artificial endothelial glycocalyx regeneration model to arrest endothelial glycocalyx degradation. (return to top)
Project 5. Biopolymer microthreads and biomimetic scaffolds enhance muscle regeneration (Advisor: George Pins, Biomedical Engineering). A total of 65.8 million Americans suffer from musculoskeletal injuries annually, with treatment costs exceeding 176 billion dollars. The Pins laboratory is developing novel technologies for 3D printing fibrin microthreads and composite scaffolds that mimic the structural, mechanical, and biochemical signaling cues of native tissue that will promote functional muscle regeneration. Potential project areas include studying scaffold stiffness and degradation rate as a function of fibrin concentration or crosslinking, characterizing scaffold biophysical properties by microfabricating topographic into the composites to enhance cellular alignment, and optimizing the inclusion of biochemical signaling cues (e.g., FGF2, IGF-1) to enhance cell proliferation or angiogenesis on the scaffolds. (return to top)
Project 6. Microtechnology tools to observe in vivo neuronal and behavioral responses to precise stimulation (Advisor: Dirk Albrecht, Biomedical Engineering). Neuropsychiatric disorders and brain injuries reduce quality of life for millions globally, resulting in more disease-affected life years than cancer or cardiovascular diseases (WHO). Electrical activity in neural circuits of the brain is constantly modulated by each of our 100 billion neurons, as they adjust their sensitivity or “excitability” to incoming signals. How this regulation occurs, in normal, injured, and disease conditions, is the focus of our research lab. Over the past decade, we developed several tools and methods to record live brain activity in intact, living C. elegans nematodes, the smallest organism with a fully-mapped network of 302 neurons that act like human neurons. By automating stimulation parameters, we directly measure many neural phenomena in hundreds of animals at once. To observe the effect of an injury, disease, or treatment, we stimulate the animals before and after and observe if responses to identical inputs gets stronger (meaning neurons became more excitable or more sensitive to the input) or weaker (less excitable). We are currently focusing on traumatic brain injury (TBI) and deep brain stimulation (DBS) to understand the changes in brain function that occur. (return to top)
Project 7. Establishing biophysical properties of bacterial biofilm infections (Advisor: Elizabeth Stewart, Chemical Engineering). Bacterial biofilms—structured communities of bacteria cells encapsulated in self-produced matrix materials—are frequently responsible for infections on biomedical devices and in chronic wounds. Biofilms are much more resistant to treatment with conventional antibiotics than individual bacterial cells and are, in turn, responsible for chronic and persistent infections. The main goal of our research is to establish and exploit biophysical properties of bacterial biofilms to enable the development of novel targets for infection prevention and control. Specific research questions may include: How are local biofilm microstructure and mechanics impacted by physiological shear stress? How do host biopolymers (e.g., fibronectin, collagen) effect local biofilm microstructure and mechanics? How do human peptides (i.e., LL37) influence local biofilm microstructure and mechanics? (return to top)
Project 8. Effect of mechanical strain on changes to distal radius microarchitecture (Advisor: Karen Troy, Biomedical Engineering). Physical activity produces mechanical strains within bone that are known to be osteogenic. Strain rate and strain magnitude are two factors that appear to be important in this process. The Troy lab is quantifying how bones are loaded in the body when people perform various types of activities thought to enhance bone health (for example, jumping and hopping). To this end, they have collected motion capture and force platform data on research volunteers performing these types of activities with different instruction sets. They have also collected high resolution imaging data of these participants’ lower extremity bone, and information about bone-loading physical activity history. Each student will be given a specific question to answer, which is related to the data set in question. For example, a student might have a goal of comparing the effect of jump height on knee biomechanics, including peak knee moments, impulses, and power. Another student might examine the relationship between hopping power and physical activity history. Students will complete Human Subjects Research Training through the CITI program. Students will be trained on data reconstruction and analysis techniques for the Vicon motion capture system and Visual3D. (return to top)
Project 9. Model extracellular matrix heterogeneity in fibrotic pancreatic tumors in vitro (Advisor: Catherine Whittington, Biomedical Engineering). As tumors grow and progress toward a metastatic state, the tumor extracellular matrix becomes stiffer and more heterogeneously organized. The overall project will focus on evaluating the response of cancer cell lines and/or stromal cell lines (e.g., fibroblasts, lymphatic endothelial cells) to ECM coated substrates of varying stiffness and heterogeneity using an in vitro model based on a minimal matrix scar system. Potential project areas include studying pancreatic tumor cell behavior on gels of different stiffness levels, studying different tumor cell or stromal cell populations with varied ECM coatings (to reflect tissue or disease specificity), and evaluating combined effects of stiffness changes with tissue/disease-specific ECM coatings for two different tumor types. (return to top)
Project 10. Ultrasound sensing of muscles for prosthetics control (Advisor: Haichong “Kai” Zhang, Biomedical Engineering and Robotics Engineering). Amputation in the arm results in decreased capability for individuals to manipulate their surroundings effectively. Advances in active prostheses have sought to augment these individuals with a prosthetic that returns some, but ideally all, functionality back to the individual. Sensors such as EMGs exist to provide information on the muscles located directly beneath the skin. However, the data they can provide is limited by muscle placement and their susceptibility to crosstalk and signal attenuation. Through the utilization of ultrasound images, assessments can be made on the muscles state and their effect on the downstream finger movements. This project aims to explore use of ultrasound in prosthetic control to achieve the improved sensitivity for prosthetics control. Potential technology development areas include optimizing the configuration of mounting the ultrasound sensor on human subjects, developing the robust hand configuration classification algorithms, and system integration for the performance demonstration with prosthetics. (return to top)
Project 11. Development of a physiologically mock loop for tricuspid valve regurgitation (Advisor: Alan Wei, Biomedical Engineering). Tricuspid regurgitation (TR) is a common condition that is expected to become more prevalent as the population ages. Effective management of TR relies on accurate assessment of the tricuspid valve orifice area (TVA). The most common way to measure TVA non-invasively is with Doppler echocardiography. One method of Doppler echocardiography is proximal iso-velocity surface area (PISA). However, the accuracy of PISA has been questioned by some experts, and there is ongoing research into new quantitative assessment techniques for TR. Any new medical device or technology, as well as any new in vivo measurement technique, must be rigorously tested in the laboratory, in animal models, and in clinical trials before it can be approved for general use by the FDA. The goal of this project is to assist in developing an in vitro experimental facility that will enable in vitro evaluation of novel TR measurement techniques.. (return to top)
Project 12. 3D-Printing of Micropatterned Scaffolds For Oriented Tissue Regeneration (Advisor: Yonghui Ding, Biomedical Engineering). Creating biomaterial scaffolds with specific physicochemical properties that guide tissue regeneration is a promising approach for repairing damaged or diseased tissues. Many tissues in the body, such as arteries, muscles, tendons, nerves, possess a distinctive spatial organization of cells, which is essential for their specific mechanical and biological functions. The ability to regenerate tissues in a way that mirrors such spatial organization is essential for reinstating their unique functional characteristics. Surface topography can provide potent guidance on the organization and function at both cellular and tissue levels, known as contact guidance. Fabrication of surface microtopography, especially at the single-cell scale, on three-dimensional (3D) objects with curved surfaces, such as 3D scaffolds, remains an enormous challenge. Our lab developed a unique 3D printing technology, named micro continuous liquid interface production (μCLIP), to produce scaffolds with well-defined topographical patterns. A potential project for an REU will be the design and fabrication of scaffolds with micropatterns featuring various sizes and geometries for the modulation of cell behavior and the regeneration of vascular tissues. (return to top)
Project 13. Delivery of luciferase-producing messenger RNA loaded lipid nanoparticles to placental trophoblast cells (Advisor: Christina Bailey-Hytholt, Chemical Engineering). The placenta plays an important role during pregnancy, yet it remains one of the least understood human organs. The main cell type composing the placenta, trophoblast cells, have important functions including nutrient and waste transport, invading the endometrium to anchor the placenta, and remodeling the vasculature for adequate blood flow. Placental abnormalities can often result in pregnancy-related complications. Controlled delivery of therapeutics to the placenta, while minimizing fetal exposure, is needed to improve treatments for pregnancy-related complications. In this project, we aim to formulate lipid nanoparticles (LNPs) loaded with a nucleic acid (e.g. messenger RNA (mRNA)) for delivery to placental trophoblast cells. LNPs are formulated using a microfluidic mixing channel and are then characterized by their size, charge, and encapsulation efficiency. After formulation, uptake studies with trophoblast cells are performed and gene expression for luciferase, an oxidative enzyme that produces bioluminescence, is assessed to determine successful transfection. Further, different LNP formulations are to be compared, as well as different placental cell types. Ultimately, this project seeks to advance prenatal therapeutic options to improve long-term health outcomes. (return to top)
Project 14. AirBaby & NutriBaby Technologies to Improve Preterm Health (Advisor: Solomon Mensah, Biomedical Engineering).
Project 15. Building AI-driven techniques for smartphone-acquired biomedical image analysis (Advisor: Emmanuel Agu, Computer Science). There are two potential areas of investigation within this topical area.
AI-driven Smartphone wound healing assessment system: Researchers at WPI and at the UMass Medical school have been researching and developing a smartphone-based wound app that utilizes AI to analyze smartphone wound images taken by visiting nurses in the patient’s home. At the push of a button, the wound app’s AI standardizes care by automatically scoring healing progress and flagging problematic cases to be referred for specialty wound care to avoid amputations. The smartphone wound system also detects the type of wound, pressure ulcer stage and the wound size all from an image.
AI-driven methods to analyze echocardiograms (heart ultrasounds) to detect weak hearts (low Ejection Fraction EF) and Hypertrophic Cardiomyopathy (HCM) were created by my researchers at WPI, the Beth Israel Deaconess Medical Center (BIDMC, a branch of the Harvard Medical School) and Boston Medical Center. HCM is the most common inherited heart condition that affects over 500,000 Americans but is severely underdiagnosed with only 1 in 13 cases detected. Hearts with low EF do not pump blood effectively and are at risk for heart failure. HCM causes the heart muscles to stiffen, making it hard to pump blood. Untreated, HCM can lead to death. At the push of a button by a non-expert, our AI models can detect weak ejection fraction and HCM from a heart ultrasound video with accuracies of over 90 and 95 percent, respectively.