Inclusion and Innovation in Medical Devices Projects

By conducting hands-on experiments, students learn about cutting-edge engineering and technologies relevant to medical problems and the development of medical devices. They are exposed to multidisciplinary research, how it is structured and implemented, and how to work and communicate within a team with very diverse backgrounds. Students also learn to think about problems creatively and actively pursue their research objectives by seeking input from experts, trying out new approaches, and developing skills to delve deeper into their problems. Students will document their efforts, writing up the outcomes for conference abstracts and papers, among others.

The REU thematic elements of this program are inclusion, innovation, and medical devices. The research project offerings go beyond medical devices because it is important to understand physiological environments to innovate solutions, and the solutions should not be constrained by the method. In line with our four intellectual foci — learning, innovating, exploring, and applying — we offer various research projects that the students can choose from.

• Project 1. Computational Strategies for Characterizing Sensory Neuron Phenotypes Based on Extracellular Electrophysiology
• Project 2. Behavioral, Biomolecular, and Immunoarchitectural Characterization of Amputation Neuroma
• Project 3. Laser SpeckLe field Microscopy (SLIM) for 3-dimensional Micro-mechanical Imaging of the Extra-Cellular Matrix (ECM)
• Project 4. Optimizing Intranasal Drug Delivery for Targeted Therapeutics
• Project 5. Mapping the current processes of cervical and breast cancer screening for Hispanics in a rural state.
• Project 6. Evaluating the Impact of High School Research Experiences in Medical Devices on Science, Technology, Engineering, and Math (STEM) Identity Formation
• Project 7. Plant-Based Scaffolds for Tissue Engineering Applications
• Project 8. Organoid-based microbe-epithelial cell coculture model for developing personalized therapies for inflammatory diseases
• Project 9. Development of Tissue Sampling Devices for Assembling Skin Constructs for Regenerating Skin
• Project 10. Development of Systems and Methods for Continuous Noninvasive Monitoring of Cellular Oxygen Utilization

Project 1. Computational Strategies for Characterizing Sensory Neuron Phenotypes Based on Extracellular Electrophysiology

Faculty Mentor: Professor Bryan Black

Students working on this project will help develop or validate computational tools for analyzing multi-parametric phenotypic data sets collected from Human induced pluripotent stem cells (hiPSC) models of acute and inflammatory nociception. The overarching goal of this funded research is to develop and characterize a novel phenotypic model of acute and chronic nociception based on hiPSC sensory neurons cultured and differentiated on microelectrode arrays (MEAs). However, the currently proposed methods of analysis may not capture the complexity of the MEA data or how it relates to biomolecular data sets. Therefore, there is a need in our lab and in the field of pain science and neuroscience research to develop or validate novel statistical approaches to extracellular electrophysiology data analysis (e.g., hierarchical clustering analysis) and correspond these outcomes with biomolecular assays. This project will provide students the opportunity to learn extracellular electrophysiology data collection, signal processing and filtering, Matlab coding, and statistical tools for multi-parametric analysis.

Project 2. Behavioral, Biomolecular, and Immunoarchitectural Characterization of Amputation Neuroma

Faculty Mentor: Professor Bryan Black

In collaboration with clinicians at Brigham and Women’s Hospital in Boston, Massachusetts, students will help collect and analyze behavioral, secretomic, and immuno-architectural data from animal models of traumatic injury / amputation pain. The overarching goal of this funded research is to better understand the histological and architectural features of traumatic/amputation neuroma – a benign peripheral nerve tumor that serves as a focal point for pain in many patients. To do so, we employ an established rodent model of amputation pain to develop and characterize symptomatic neuromas. Additionally, students will have the opportunity to interact with clinicians and perform preliminary histochemical analyses from human neuroma samples.

During this project, the students will learn clinical outcomes related to traumatic peripheral nerve injury and amputation, clinical strategies for intervention and/or pain management, as well as technical skills related to antibody staining and subsequent image analysis/quantification. The data processed in this project will inform preclinical and, subsequently, clinical/commercial strategies for traumatic neuroma intervention.

Project 3: Laser SpeckLe field Microscopy (SLIM) for 3-dimensional Micro-mechanical Imaging of the Extra-Cellular Matrix (ECM)

Faculty Mentor: Professor Zeinab Hajjarian

Excessive and irregular micro-mechanical remodeling of the ECM is implicated in a broad spectrum of pathologies, including cardiovascular disease, fibrotic disorders, and cancer, which together account for over 50% of deaths worldwide. Nevertheless, our understanding of the underlying mechanisms is severely limited as no imaging tools are currently available for micromechanical mapping of the ECM at length scales pertinent to cells. This project aims to develop and validate a laser SpeckLe fIeld Microrheology (SLIM) technology for micromechanical tissue mapping with high spatial resolution and long depth range. The proposed technology is based on measuring the time-varying speckle intensity fluctuations. A speckle is a grainy intensity pattern formed when a coherent laser beam is backscattered from tissue. Brownian displacements of scattering particles within the ECM dynamically modulate the speckle fluctuations. These fluctuations are intimately related to the viscoelastic properties of imaged tissue. In compliant regions, unrestricted Brownian displacements provoke rapidly fluctuating speckle spots, whereas, in rigid areas, restrained motions elicit limited intensity variations of speckle grains. The capability of SLIM for 3-dimensional, high-resolution, micromechanical imaging of the ECM will provide new insight and scientific knowledge regarding the micro-mechanical basis of pathogenesis at the onset of disease. It will also allow the testing of multiple hypotheses of high clinical impact about therapeutic targeting of the ECM and the downstream mechanical-transduction signaling pathways, which could likely prevent the pathogenesis at its source. During this project, students will be deeply engaged in the setup of the optical instrumentation and creating image reconstruction algorithms. Additionally, they will be involved in validating and benchmarking the performance parameters of the SLIM modality. This will be accomplished by characterizing hydrogel phantoms and biological tissues using the SLIM technique and well-established mechanical testing methods.

Project 4. Optimizing Intranasal Drug Delivery for Targeted Therapeutics

Faculty Mentor: Professor Jinxiang Xi

Intranasal drug delivery is emerging as a popular method for administering medications due to its non-invasive nature, ease of self-administration, and its ability to deliver therapeutics to highly vascularized regions of the nasal cavity for rapid absorption. This method is being used to treat various conditions, including neurodegenerative diseases through nose-to-brain (N2B) delivery, mucosal protection, and more, highlighting its potential as a versatile and efficient delivery system. This project focuses on optimizing intranasal drug delivery for specific therapeutic targets within the nasal cavity. Students will be introduced to the anatomy and physiology of the nasal cavity and learn about the unique challenges and opportunities it presents for drug delivery.

Participants will:

• Explore in vitro testing techniques used to evaluate and optimize medication delivery to targeted regions within the nasal cavity.
• Learn about the design and development of drug formulations and delivery devices tailored for intranasal use.
• Gain hands-on experience with computational engineering tools such as ANSYS and COMSOL Multiphysics to perform simulations that inform the design and engineering of nasal drug delivery techniques and devices.
• Engage in supervised experimental studies using high-fidelity anatomically accurate nasal cavity geometries, 3D-printed models, and visualization techniques to analyze and refine delivery parameters.

By the end of the program, students will have developed delivery parameters to ensure doses are efficiently delivered to specific regions within the nasal cavity. Computational simulations will complement these findings, providing a holistic approach to optimizing intranasal drug delivery methods.

Project 5. Mapping the current processes of cervical and breast cancer screening for Hispanics in a rural state.

Faculty Mentor: Professor David Claudio

Summary: This project will focus on creating a Current State and Future State Value Stream Map (VSM) of the processes Hispanic females go through for cervical and breast cancer screening in Gallatin County, Montana. A student will learn how to create current and future state VSM. Concepts of lean manufacturing/healthcare will also be taught to the student. The student will then interview several entities via Zoom to decipher the patient, provider, and information flow for the current state VSM. The student will then brainstorm ideas on improving current processes and creating a future state VSM. A draft of a conference or journal article will be required as a final product. Fluency in Spanish is preferred but not required.

Project 6. Evaluating the Impact of High School Research Experiences in Medical Devices on Science, Technology, Engineering, and Math (STEM) Identity Formation

Faculty Mentor: Professor Yanfen Li

This project explores how professional development and orientation programs shape high school students' experiences in research and influence their STEM identity formation. Participants will analyze program data, conduct surveys and interviews with students and mentors, and examine the relationship between training modules and research experiences on students' self-perception as STEM learners and future professionals. The project aims to identify strategies that foster students’ confidence, sense of belonging, and long-term engagement in STEM.

Project 7. Plant-Based Scaffolds for Tissue Engineering Applications

Faculty Mentor: Professor Yanfen Li

In tissue engineering applications, scaffolds are necessary to provide structure and rigidity to the new tissue and guide cells toward desirable functions. Instead of artificially replicating the complexity of scaffolds in nature, it is possible to repurpose existing plant matter by removing the native cells (decellularization), leaving behind a natural scaffold for new cells to inhabit. This project aims to analyze the mechanical properties of several plant-based scaffolds to optimize the matching of scaffolds to future intended tissues. In this project, students will learn how to decellularize plants, how to perform cell culture, and how to conduct a variety of mechanical testing. Students will also learn how to translate their learning to develop an at-home learning kit that teaches high school and undergraduate students about tissue decellularization.

Project 8. Organoid-based microbe-epithelial cell coculture model for developing personalized therapies for inflammatory diseases

Faculty Mentor: Professor Soumita Das

The interactions between gut microbes and host cellular pathways are essential in enteric infections, gastrointestinal diseases, and other chronic diseases. To understand disease pathogenesis, developing a cell model that mimics physiological situations and is closer to humans than the existing animal models is essential. Utilizing recent developments in stem-cell biology, we have developed an organoid-based cell model from humans or mice that is cocultured with immune/nonimmune cells and microbes associated with the disease. This model is useful to investigate mechanisms for gastrointestinal inflammatory diseases, both oncogenic and non-oncogenic. In collaboration with Department Chair Walfre Franco’s lab in the Department of Biomedical Engineering, we are modifying this model in a semi-high-throughput (HTP) format by adding microfluidics to the tissue culture plate and optimizing the microenvironment. At the start of the project, the semi-HTP inflammatory bowel disease (IBD) model will be used to identify new therapeutic targets, understand the impact of microbes, and screen existing drugs and nutritional supplements. This project needs collaboration with scientists from diverse backgrounds with expertise in biotechnology, cell biology, microbiology, and computational science. Functional assays, including gut barrier integrity, transcriptional profiles, and multiplex cytokine assays, will validate the predicted targets for IBD. The semi-HTP format of the cell model with several patient-derived organoids could help develop personalized therapies in the future. Students' activities include building microfluidic chips, imaging particle tracers, and inputting experimental measurements to computational models to characterize forces around organoid models. Students will learn about microfluidic chip fabrication, particle image velocimetry, computer fluid dynamics, and mechanotransduction.

Project 9. Development of Tissue Sampling Devices for Assembling Skin Constructs for Regenerating Skin

Faculty Mentor: Professor Walfre Franco

Despite decades of concerted efforts to develop alternatives, autologous skin grafting remains the gold standard for wound repair. Still, it comes with the cost of substantial and often permanent donor-site morbidity. Full-thickness skin tissue micro-grafts can be extracted with minimal donor site morbidity. Can skin be copied if we extract full-thickness skin micro grafts from a donor site, insert them into an optimized scaffold, and graft the skin copy? This project focuses on developing tissue sampling devices for assembling skin constructs for regenerating skin. Students will learn about device design, prototyping, and testing of functional blocks. Students will assist with developing skin grafting devices by using computer-aided design software, additive manufacturing, or 3D printing, among other fabrication methods.

Project 10. Development of Systems and Methods for Continuous Noninvasive Monitoring of Cellular Oxygen Utilization

Faculty Mentor: Professor Walfre Franco

More than half of all hospital deaths are caused by sepsis, and patients who die of sepsis succumb to the ensuing multiorgan failure. As oxygen utilization in a cell becomes deficient, changes in mitochondrial redox state precede cellular, tissue, and organ function changes. Mitochondrial damage occurs during sepsis, such as the impairment of oxygen extraction and utilization, and the severity of mitochondrial dysfunction has been shown to correlate with increased patient mortality. Therefore, a significant need exists for methods to evaluate mitochondrial utilization of oxygen continuously. This project focuses on developing optical, acoustic, and machine-learning systems and methods for continuous noninvasive monitoring and real-time analysis of cellular oxygen utilization. Students will help develop computer algorithms and photoacoustic methods for quantifying and analyzing variations in the optical environment of tissues. Students will learn about computational modeling, machine learning, and how light is used to measure tissue oxygenation and could be used to measure oxygen consumption.