Biomedical Engineering and Bioengineering Commons^™

Using Mechanical Interventions To Enhance Drug Transport To Bone Tumors, Michelle Gelbs

Dissertations and Theses

Bone metastasis occurs when cancer cells spread from a primary site to a secondary location in bone. Current treatments for metastatic bone tumors typically involve systemic chemotherapy, bisphosphonates, radiotherapy, or surgery; however, due to morphological changes in the tumor microenvironment and elevated interstitial fluid pressure, tissue penetration of therapeutic agents is often more limited in cancerous tumors compared to normal tissue. Weight-bearing mechanical loading applied to bone, as well as other mechanical stimulations such as vibration, have been shown to cause loading-induced bone deformations that increase convective transport via interstitial fluid flow. We hypothesize that mechanical loading can increase the …

Optimizing Transcranial Focused Ultrasound: Calibration, Neuro Navigation, And Bold Fmri Evidence Of Neuromodulation, Amilcar J. Malave

Dissertations and Theses

This thesis presents the development, calibration, and initial implementation of transcranial focused ultrasound (tFUS) for neuromodulation in a human study. The primary objectives were to design a system capable of delivering precise and safe ultrasound stimulation to targeted brain regions and to conduct preliminary trials to assess its effects on brain activity. A custom calibration device was developed to ensure accurate measurement of acoustic pressure, addressing challenges such as voltage alterations caused by changes in system impedance. Additionally, a neuro-navigation tool was created to facilitate precise targeting of the right subgenual anterior cingulate cortex (right sgACC), enabling accurate placement of …

Modulation Of Motor Learning With High-Intensity Transcranial Electric Stimulation, Gavin Hsu

Dissertations and Theses

Research thus far on noninvasive, transcranial electric stimulation have produced mixed results from in vivo human experiments. This work tests the hypothesis that applying higher stimulation intensities would induce intracranial electric fields that more closely match the higher magnitudes used in animal and in vitro studies and subsequently yield more robust effects. As done commonly in the literature, we targeted the motor cortex (M1), specifically in the context of neuroplastic changes taking place during motor learning in healthy adult humans. This work also seeks a better understanding of the neural correlates underlying motor skill learning.

Through multiple large-sample studies, this …

Mechanisms For Regenerative Intervertebral Disc Healing During Early Growth In Mice, Danielle N. D'Erminio

Dissertations and Theses

Annulus Fibrosus (AF) defects of intervertebral discs (IVDs) cause painful disability, for example when herniated tissue compresses against adjacent nerves. Discectomy, the current standard of treatment to address herniation, does not repair AF defects and can result in re-herniation and recurrent pain. As such there is a need for improved AF repair strategies. It has previously been established that neonatal mice functionally regenerate following severe AF injury providing a model of successful innate AF repair processes that contrasts the poor healing of adult mice. This dissertation focuses on identifying mechanisms of AF regenerative healing in neonatal mice subjected to severe …

Development Of Glutathione-Responsive Disulfide-Containing Poly(Beta-Amino Esters) With Varied Hydrophilicity And Acrylate Functionality, Anastasiia Aronova

Theses and Dissertations--Chemical and Materials Engineering

Smart biomaterials are becoming promising for therapeutic deliveries due to their ability to respond to changes in the environment. Redox-responsive hydrogels are a promising type of smart polymer that can swell and degrade according to cellular oxidative stress levels. Glutathione, abundant in cells, is crucial in redox-responsive biomaterials, serving as a key reactive molecule. This study explored the degradation kinetics of glutathione-responsive poly(β-amino ester) (PBAE) polymers created through a single-step Michael addition. We examined how disulfide content influences the degradation kinetics of these PBAE networks. Additionally, we investigated how the hydrophilicity and functionality of acrylate affect the degradation of disulfide-containing …

Sustained Release Systems For Endometrial Cancer, Claire E. Rowlands

Theses and Dissertations--Chemical and Materials Engineering

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is the most common cancer of female reproductive organs. From 2007-2016 there has been a global rise in incidence of EC of 1.3 %. Typically, EC is treated with surgery, but at later stages surgery is less effective requiring chemotherapy and/or radiation therapy. These treatment options are less effective than surgery and there are very few FDA approved chemotherapies for EC. The minuscule number of effective treatment options as well as an increase in incidence shows the need for creating improved treatments for EC. There has been …

On The Modes Of Nanosecond Pulsed Plasmas For Combustion Ignition Of Quiescent Ch₄-Air Mixtures, Chunqi Jiang, Akash C. Dhotre, Meimei Lai, Sayan Biswas, James R. Macdonald, Isaac W. Ekoto

Bioelectrics Publications

The effect of transient plasma modes on ignition kernel development are discussed here for a quiescent CH₄-air combustion model system. A 10 ns high-voltage pulse was applied to a pin-to-pin electrode in lean fuel-air mixtures at room temperature and atmospheric pressure. High-impedance streamer, transient spark and low-impedance spark discharges were identified based on pulse waveforms of voltage and current. A sustained ignition kernel expansion was observed when the plasma discharge transitioned into a transient spark or spark discharge. The minimum ignition energy was obtained at the transient spark mode, which has less than a third of the energy …

Simultaneous Evaluation Of Tibiofemoral And Patellofemoral Mechanics In Total Knee Arthroplasty: A Combined Experimental And Computational Approach, Yashar A. Behnam, Ahilan Anantha Krishnan, Hayden Wilson, Chadd W. Clary

Center for Orthopaedic Biomechanics: Faculty Scholarship

Contemporary total knee arthroplasty (TKA) has not fully restored natural patellofemoral (P-F) mechanics across the patient population. Previous experimental simulations have been limited in their ability to create dynamic, unconstrained, muscle-driven P-F articulation while simultaneously controlling tibiofemoral (T-F) contact mechanics. The purpose of this study was to develop a novel experimental simulation and validate a corresponding finite element model to evaluate T-F and P-F mechanics. A commercially available wear simulator was retrofitted with custom fixturing to evaluate whole-knee TKA mechanics with varying patella heights during a simulated deep knee bend. A corresponding dynamic finite element model was developed to validate …

Biom 1720: Introduction To Biomedical Engineering Tools, Stephen Strain

Biomedical Engineering Syllabi Archive

Course Description: Use of computer tools for data analysis, presentation, documentation; introduction to programming; individual and group design projects.

Biom 3110: Medical Physiology (Syllabus), Bradford D. Pendley

Biomedical Engineering Syllabi Archive

Course Description: Basic principles of human physiology and how these are applied in medicine and biomedical engineering problem and devices; physiological principles using appropriate mathematical and engineering models to construct an understanding of how the body works as an integrated system.

Biom 4784: Biomedical Design Studio (Syllabus), Amy Curry

Biomedical Engineering Syllabi Archive

Course Description: Laboratory experience dedicated to the design, development, and fabrication of a final prototype for use in conducting engineering analysis and design loop feedback. Responsibilities will include frequent team meetings, mentor advising, and group brainstorming along with prototype designing, technical drawings, fabrication, engineering analysis, and verification/validation. Deliverables for each team will be a prototype, final design specification report with engineering reports, and a final team presentation.

Biom 4410/Mech 4397: Engineering Practicum (Syllabus), Sheila Moses, Jeff Marchetta, Amy Curry

Biomedical Engineering Syllabi Archive

Course Description: Preparation for professional practice through experiential learning under the supervision of an experienced engineer with oversight by a member of the department’s faculty. Regular reporting throughout course required.

Biom 4782: Biomedical Design Practicum (Syllabus), Amy Curry

Biomedical Engineering Syllabi Archive

Course Description: Practical application of biomedical design principles with emphasis on project management, teamwork, prototype production, risk analysis and management, technical drawings, patent review with claim development, market analysis, regulatory issues, professional and ethical responsibilities of a biomedical engineer, engineering analysis/reports, incorporation of standards, prototype verification/validation, and presentation skills.

Insights Into The Heart Microstructure: A Case Study, Sarah Bulger

Honors Undergraduate Theses

This thesis focuses on better understanding the structures of the heart at the micro-scale. Cardiomyocytes and the branching of cardiomyocytes are of specific interest. A literature review was performed to extract key information on cardiomyocyte size, the branching type and frequency of cardiomyocytes, and cardiomyocytes' organization in general. The purpose of conducting the literature review was to find quantifiable data on the micro-structure of the heart. Three studies in particular provided data on the branching of cardiomyocytes. Two of these studies were conducted on rat hearts, while one other study was conducted on human hearts. The methods and terminology between …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

Dna I-Motifs: Biophysical Characterization And Structure-Property Correlation As Foundation For Functional Material Design, Alexander Minasyan

Graduate Research Theses & Dissertations

Over the past decades, nucleic acids have emerged as crucial frameworks with significance in biological systems and functional material engineering. Cytosine-rich deoxyribonucleotide sequences can form quadruplex structures a.k.a. i-motifs. Recently, i-motifs have attracted scientific interest in biological and material design areas.

In this work, we systematically investigate an effect of structured and unstructured modifications such as hairpins, stems, loops and overhangs on the kinetic and thermodynamic properties of DNA i-motifs. We demonstrate that the modifications can influence i-motif’s stability and folding/unfolding rates: thus, double stranded stems and hairpins are the best at stabilizing i-motifs and increasing kinetic rates of folding. …

Advancements In Sarcoma- And Nerve-Specific Fluorescence Imaging For Surgical Guidance, Kendra A. Hebert

Dartmouth College Master’s Theses

Fluorescence guided surgery (FGS) is an evolving field that aims to improve patient outcomes by using fluorophores to identify important tissues during surgery, such as tumors and nerves. In this thesis work, we explored different methods of identifying nerve and tumor tissues for FGS and a novel fluorescence-based method to determine the depths of these structures.

Researchers have explored using fluorescence guided surgery for surgical resection of cancerous tissues, including recent work by our group focusing on identifying soft tissue sarcomas with ABY-029, an epidermal growth factor receptor targeting probe. However, our preclinical and clinical work shows no single reporter …

De-Risking Pretreatment Of Microalgae To Produce Fuels And Chemical Co-Products, Jacob S. Kruger, Skylar Schutter, Eric P. Knoshaug, Bonnie Panczak, Hannah Alt, Alicia Sowell, Stafanie Van Wychen, Matthew Fowler, Kyoko Hirayama, Anuj Thakkar, Sandeep Kumar

Civil & Environmental Engineering Faculty Publications

Conversion of microalgae to renewable fuels and chemical co-products by pretreating and fractionation holds promise as an algal biorefinery concept, but a better understanding of the pretreatment performance as a function of algae strain and composition is necessary to de-risk algae conversion operations. Similarly, there are few examples of algae pretreatment at scales larger than the bench scale. This work aims to de-risk algal biorefinery operations by evaluating the pretreatment performance across nine different microalgae samples and five different pretreatment methods at small (5 mL) scale and further de-risk the operation by scaling pretreatment for one species to the 80 …

Reevaluating The Paradox: Does Low-Dose Radiation From A-Bombs Affect Lifespan And Cancer Mortality?, Razieh Rashidfar, Zeynab Seyedi Sarhad, Seyed Mohammad Javad Mortazavi, Lembit Sihver

Informatics and Engineering Systems Faculty Publications

No abstract provided.

Engineering Mussel Foot Protein 5 (Mfp5) For Enhanced Adhesive Performance In Tendon And Bone Repair, Ziyue Zhu

McKelvey School of Engineering Graduate Student Theses & Dissertations

This study explores the development of Mussel Foot Protein 5 (MFP5) bioadhesives to improve tendon-to-tendon and tendon-to-bone adhesive outcomes. MFP5, known for its underwater adhesive properties, was synthesized using recombinant techniques and optimized through coacervation and cross-linking. Adhesion tests demonstrated the superior performance of the optimized MFP5 adhesive on the tendon and bone samples. Improved protein concentration testing and purification methods enhanced MFP5 yield and consistency. Future research will focus on further standardization, exploring alternative purification methods, and evaluating the adhesive's performance in animal models. This study lays a foundation for developing robust MFP5-based bioadhesives, potentially revolutionizing surgical repair techniques …

In Vivo Measurement Of Nadh Fluorescence Lifetime In Skeletal Muscle Via Fiber-Coupled Time-Correlated Single Photon Counting, Kathryn M. Priest, Jacob V. Schluns, Nathania Nischal, Colton L. Gattis, Jeffery C. Wolchok, Timothy J. Muldoon

Biomedical Engineering Faculty Publications and Presentations

Nicotinamide adenine dinucleotide (NADH) is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS). NADH is autofluorescent, and its fluorescence lifetime can be used to infer metabolic dynamics in living cells. Fiber-coupled time-correlated single photon counting (TCSPC) equipped with an implantable needle probe can be used to measure NADH lifetime in vivo, enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration. This study illustrates a proof of concept for point-based, minimally-invasive NADH fluorescence lifetime measurement in vivo. Volumetric muscle loss (VML) injuries were …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

Method For Continuous Fabrication Of Multi-Functional Nanogels, Hu Yang, Da Huang

Patents

Nanogels and methods of synthesizing and using these nanogels are provided. The nanogels are formed by mixing a building block (e.g., polymer), crosslinker, preferably a target (e.g., biomedical compound or molecule), and a solvent in a multi-inlet vortex mixer, so as to cause the polymer and crosslinker to react and form a chemically crosslinked polymer network. In embodiments including a target, the target will be interspersed in and among that network and can be physically embedded and/or chemically bound therein.

A 3d Co-Culture Model Of Senescent Cell Burden And Salivary Gland Fibrosis, Stephen Rose

Electronic Theses & Dissertations (2024 - present)

Patients with head and neck cancer often suffer collateral radiation damage to the salivary glands, leading to fibrosis. Histological examinations indicate that radiation encourages fibrosis by promoting cellular changes leading to both senescent and myofibroblast phenotypes, coupled with a significant loss of regenerative and acinar cells. Chronic hypofunction remains a primary concern, even with modified radiation approaches to sparing salivary glands. Current treatments primarily offer symptomatic relief without rectifying irreversible glandular tissue damage. This limitation arises, in part, from a deficiency in predictive preclinical models to study this multifaceted problem.

We introduce a 3D in vitro microtissue model to address …

The Effect Of Phase-Separated Microstructures On Cell Migration In 3d Dextran Hydrogels, Jenifer Sidhwa

Honors Theses and Capstones

No abstract provided.

Flexible Fitting Of Alphafold2-Predicted Models To Cryo-Em Density Maps Using Elastic Network Models: A Methodological Affirmation, Maytha Alshammari, Jing He, Willy Wriggers

Computer Science Faculty Publications

Motivation: This study investigates the flexible refinement of AlphaFold2 models against corresponding cryo-electron microscopy (cryo-EM) maps using normal modes derived from elastic network models (ENMs) as basis functions for displacement. AlphaFold2 generally predicts highly accurate structures, but 18 of the 137 models of isolated chains exhibit a TM-score below 0.80. We achieved a significant improvement in four of these deviating structures and used them to systematically optimize the parameters of the ENM motion model.

Results: We successfully refined four AlphaFold2 models with notable discrepancies: lipid-preserved respiratory supercomplex (TM-score increased from 0.52 to 0.69), flagellar L-ring protein (TM-score increased from 0.53 …

Enhanced Skin Cancer Diagnosis Through Grid Search Algorithm-Optimized Deep Learning Models For Skin Lesion Analysis, Rudresh Pillai, Neha Sharma, Sheifali Gupta, Deepali Gupta, Sapna Juneja, Saurav Malik, Hong Qin, Mohammed S. Alqahtani, Amel Ksibi

Computer Science Faculty Publications

Skin cancer is a widespread and perilous disease that necessitates prompt and precise detection for successful treatment. This research introduces a thorough method for identifying skin lesions by utilizing sophisticated deep learning (DL) techniques. The study utilizes three convolutional neural networks (CNNs)-CNN1, CNN2, and CNN3-each assigned to a distinct categorization job. Task 1 involves binary classification to determine whether skin lesions are present or absent. Task 2 involves distinguishing between benign and malignant lesions. Task 3 involves multiclass classification of skin lesion images to identify the precise type of skin lesion from a set of seven categories. The most optimal …

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

Domain Adaptive Federated Learning For Multi-Institution Molecular Mutation Prediction And Bias Identification, W. Farzana, M. A. Witherow, I. Longoria, M. S. Sadique, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Deep learning models have shown potential in medical image analysis tasks. However, training a generalized deep learning model requires huge amounts of patient data that is usually gathered from multiple institutions which may raise privacy concerns. Federated learning (FL) provides an alternative to sharing data across institutions. Nonetheless, FL is susceptible to a few challenges including inversion attacks on model weights, heterogenous data distributions, and bias. This study addresses heterogeneity and bias issues for multi-institution patient data by proposing domain adaptive FL modeling using several radiomics (volume, fractal, texture) features for O6-methylguanine-DNA methyltransferase (MGMT) classification across multiple institutions. The proposed …

Matrix Stiffness Sensing By Nascent Adhesions And The Role Of Riam In Adhesion Assembly, Nikhil Mittal

Dissertations, Master's Theses and Master's Reports

Mechanical stiffness of the extracellular matrix (ECM) impacts many cellular functions such as proliferation, migration, and differentiation. ECM stiffness is sensed by a cell via integrin-based focal adhesions (FAs) by changing conformation and biochemical activities of molecules within FAs by the exchange of the force between the ECM and filamentous actin (F-actin). Cells in turn respond to this stiffness by generating traction force that plays an important role in many biological events such as tissue morphogenesis, stem cell differentiation, wound healing, and cancer cell metastasis. The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. Understanding stiffness sensing …