Molecular, Cellular, and Tissue Engineering Commons^™

The Effects Of Adipose Tissue Trauma On Vascular Function After Collateral Arteriogenesis, Nathan Tran

Biomedical Engineering

Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is characterized by arterial narrowing that reduces perfusion to the limbs. Collateral arterioles can naturally restore blood flow through a remodeling process called arteriogenesis, making it a promising therapeutic target. However, the femoral artery ligation (FAL) model used to study arteriogenesis requires surgical access deep to the inguinal fat pad, and approaches for handling the fat pad vary widely across surgeons and protocols. Since adipose tissue harbors a large population of macrophages, the immune cells that govern arteriogenesis, fat pad manipulation may introduce confounding inflammatory stimuli that disrupt …

Quantitative Fluorescence Imaging Using A Paired Agent Approach For Improving Surgical Decision Making, Sanjana Pannem

Dartmouth College Ph.D Dissertations

Surgical resection remains to be the cornerstone of treatment for most solid tumors, where the primary objective is to remove all visible and microscopic disease. However, the extent of tumor resection is inherently limited by the surgeon’s ability to distinguish tumor from normal tissue, intraoperatively. As a result, positive surgical margins (PSM), where residual tumor remains after surgery, are a common occurrence and are associated with increased recurrence, need for adjuvant therapies, dismal patient outcomes, and high healthcare costs.

Fluorescence guided surgery (FGS) has emerged as a promising technique to enhance intraoperative visualization of tumors and may help reduce the …

Advancing Computational Analysis Of Fluorescence Imaging For Head And Neck Cancer Surgical Guidance, Yao Chen

Dartmouth College Ph.D Dissertations

The main goal of surgery for head and neck squamous cell carcinoma (HNSCC) is to remove the tumor completely while preserving as much healthy tissue as possible to enhance patient survival and reduce complications. However, achieving clear surgical margins is difficult due to the complex anatomy of the head and neck and the reliance on a surgeon’s visual and tactile assessments. Recently, near-infrared (NIR) fluorescence molecular imaging has shown potential for better tumor visualization during surgery, using targeted imaging agents like epidermal growth factor receptor (EGFR) probes. This has led to the development of fluorescence-guided surgery (FGS), which helps surgeons …

Development Of Translational Microscale Systems To Interrogate How Biophysical And Biochemical Cues Alter The Phenotype Of Hormone Positive Breast Cancer, Braulio Ortega Quesada

All Dissertations

Cancer is a complicated disease and one in every three diagnoses are women with breast cancer. Recent research shows that the progression of cancer depends strongly on interactions with other non-cancerous cells and non-cellular components. Metastasis, the spread of cancer to other parts of the body, is a key step in cancer progression and makes treatment harder, leading to poor response to treatments culminating in death in ~90% of patients. This dissertation focused on creating a series of microdevices as novel pre-clinical models of breast cancer. Two different devices were fabricated to (1) study how exposing cancer cells to the …

Optimal Tissue Clearing Of Gastric Cancerous Organoids Imaged Via High Resolution Light Sheet Microscopy, Lauren D. Lieu

2025 Fall Honors Capstones Projects - Archive

While the rate of surviving a myocardial infarction has increased in the past 60 years from 60% to 90%, the rate of Americans developing chronic heart disease such as heart failure, arrhythmias, and hypertensive heart disease has risen. This has led to the development of imaging technology such as Light Sheet Microscopy (LSM) and Light Field Microscopy (LFM) to study heart contractility and congenital heart disease via models such as cancerous organoids or Zebrafish. However, LSM and LFM results are highly dependent on the quality of the staining and cleared samples. This study looks to add to the growing field …

Generation And Characterization Of Human Blood-Brain Barrier Models For Investigating Neuropsychiatric Disorders And Tumor Metastasis, Yunfei Li

Dissertations and Theses

The blood–brain barrier (BBB) is important in the normal function of the central nervous system (CNS). An altered BBB has been described in various neuropsychiatric disorders. The brain-specific microvascular endothelial cell (BMEC) is an essential structural component of the BBB. To test if integrity of the BBB formed by BMECs is compromised in 22q11.2 deletion syndrome (also called DiGeorge syndrome), which is one of the validated genetic risk factors for schizophrenia, a 2D iBBB (induced BBB) on a Transwell filter was generated from human microvascular endothelial cells (HBMECs) derived from the induced pluripotent stem cells (iPSCs) out of patients with …

Hypoxic Incubator: Improving Robustness/Reliability And Demonstrating Physiological Efficacy, Damon Dennis Tan

Master's Theses

The Microphysiological Systems Laboratory aims to develop colorectal cancer tumor models under a hypoxic environment to assess model response to pharmaceutical compounds in vitro. To perform relevant studies, researchers have attempted to use different hypoxic inducing strategies such as a nitrogen pod and hypoxic incubator to recreate in vivo physiological responses to hypoxia. However, studies would be interrupted due to incubator functionality failure. To ensure successful and physiologically relevant studies, I improved and verified the robustness and reliability of a hypoxic incubator previously designed and manufactured in the lab. Through the testing and iterating design processes, I engineered and implemented …

Calcium Analysis Of Intercellular Communications Between Alpha Cells And Delta Cells Across The Pancreatic Islet, Shichao Gao

McKelvey School of Engineering Graduate Student Theses & Dissertations

The intricate communication between different cell types within pancreatic islets plays a crucial role in regulating glucose homeostasis. Among these cellular interactions, the interplay between α cells (responsible for glucagon secretion) and δ cells (secreting somatostatin) is particularly intriguing due to the inhibitory effects of somatostatin on glucagon release. Understanding the intercellular interactions between α and δ cells may provide insights into the mechanisms underlying the coordinated regulation of blood glucose levels. In this study, we employed a multi-modal approach combining confocal imaging, image analysis, and correlation network analysis to investigate the spatial relationships and potential functional connections between α …

Utilizing Spatial Transcriptomics To Compare Gene Expression In Volumetric Muscle Loss Injury Recovery, Colton Gattis

Biomedical Engineering Undergraduate Honors Theses

Volumetric Muscle Loss (VML) injuries are known to disrupt the normal regenerative process via fibrosis leading to an extensive permanent loss of muscle function. The specific causation of this disruption remains to be defined; however, with new developments in transcriptomics, genetic trends can be identified across regions of tissue over time. This study follows VML injuries within the tibialis anterior of a mouse model for fifteen days after initial injury to attempt to identify expected transitions in healing. Genetic presence began to become more diversified as recovery progressed from four to fifteen days post injury with spatial clusters becoming globalized …

Development Of An In Vitro 3-Dimensional Co-Culture Human Colorectal Cancer Model In Microfluidic Devices, Abby Jens

Master's Theses

Colorectal cancer is the second most common cause of cancer-related deaths in the United States, with the relative 5-year survival rate for distant stage cancer being only 14%. The most common treatment for colorectal cancer is with chemotherapeutic drugs; however, the discovery of these drugs is costly, time-consuming, and often requires the use of animal models that do not yield results that translate to clinical trials. Due to these shortcomings, researchers seek to develop physiologically relevant in vitro tumor models that more accurately mimic the tumor microenvironment for cheaper and faster high-throughput drug screening. The aim of this research was …

4d Epr Oximetry Imaging For 4d Bioprinting And Tissue Engineering, Sajad Sarvari

Graduate Theses, Dissertations, and Problem Reports (ETD)

Bioprinting, akin to 3D printing, employs cell-laden hydrogels such as GelMA (Gelatine Methacrylate) and Alginate instead of plastic or resin to create biological structures. The printing process followed by subsequent tissue maturation is known as 4D bioprinting, where the fourth dimension is time. Ensuring adequate and consistent oxygen, O2, supply within 3D bioprint volume over the entire maturation period process is crucial, as even transient hypoxia can impact cellular behavior and phenotypes. However, printing of fully developed vasculature remains an unresolved technical challenge. Several approaches to chemically (peroxides) or biologically (photosynthesis) generate oxygen during bioprint maturation have been proposed. However, …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

All Dissertations

Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

A Comparison Of Optical Measurement Methods For The Growth Of S. Cerevisiae, Jackson Black

Chemical Engineering Undergraduate Honors Theses

Genetic engineering of living organisms provides the opportunity to express and harvest different proteins from cell surfaces. Yeast (S. cerevisiae) is one such organism and is capable of being grown on an industrial scale. Cellular concentration is an important parameter to monitor while fermentation processes are underway, in order to control the environment inside the growth medium and maximize yields. Spectrophotometry is a conventional method for measuring concentration, but is limited by a narrow absorbance range, and the need for on-site periodic sampling. A continuous method of measurement, as provided by Bug Labs BE2100 non-invasive biomass monitor, would …

Labeling Melanoma Cells With Black Microspheres For Improved Sensitivity In Detection Via Photoacoustic Flow Cytometry, Tori Kocsis

Electronic Theses and Dissertations

Melanoma is an aggressive form of skin cancer known for developing into metastatic disease. Current clinical diagnostics, including medical imaging and tissue biopsy, provide a poor prognosis since the cancer is in the late stages of disease progression. In recent years, photoacoustic flow cytometry has allowed for the detection of circulating melanoma cells within patient blood samples in vitro. Although this method exploits the naturally-produced melanin within the cells, it has only successfully detected highly-pigmented melanoma cell lines. Since various forms of melanoma exist, each with varying melanin concentrations, this research aims to provide a novel method for detecting lightly-pigmented …

Assessing The Potential Effectiveness Of Diffuse Reflectance Spectroscopy For Quantifying Neonatal Skin Properties Using Tissue Phantoms, Jack Murphy

Biomedical Engineering Undergraduate Honors Theses

Diffuse reflectance spectroscopy (DRS) has previously been shown to be effective at analyzing the optical characteristics of a wide variety of biological tissues, including the skin. In addition to being sensitive to the amount of blood and its oxygenation, DRS can be used to extract bilirubin levels and assess jaundice, a common complication in newborn infants. To assess its potential for being utilized in applications involving neonatal skin, we evaluated the utility of DRS for extracting hemoglobin and bilirubin concentrations from tissue phantoms. Phantom sets were created by including a known amount of scattering and by varying known concentrations of …

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

The Effects Of Microgravity On Human Endothelial Cells In Relation To Deep Vein Thrombosis, Allie Burgess

Biomedical Engineering Undergraduate Honors Theses

Deep vein thrombosis (DVT) is a condition where blood clots form in one or more of the deep veins of the body, causing leg pain and/or swelling, potentially leading to pulmonary embolism and/or stroke. The incidence of DVT among astronauts serving on the International Space Station has been shown to be greater than that of the general population, calling into question the effects of microgravity on human thrombolytic processes. Additionally, microgravity conditions have been shown to cause muscular atrophy and a decrease in muscle strength and mobility. Because collagen composes a large portion of muscle tissue, this study also assessed …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Erythrocyte Deformability In Response To Glucose Using Liquid Crystals, Jayden Goff

Biomedical Engineering Undergraduate Honors Theses

The worldwide prevalence of diabetes mellitus is rapidly increasing with about 9.3% of the adult population living with the disease. People with diabetes have trouble regulating their blood glucose levels which typically leads to hyperglycemia. Under normal physiological conditions, erythrocytes can undergo deformations in response to shear stress when passing through capillaries with a smaller diameter. Poorly managed hyperglycemia can lead to the glycosylation of erythrocyte membrane proteins and hemoglobin. This glycosylation leads to increased rigidity of the cells along with decreased deformability in response to mechanical stress; therefore, these cells have a higher susceptibility of getting stuck in the …

Clot Analogs For The Development Of Improved Treatment Methods In Ischemic Stroke, Charles A. Rieth

Biomedical Engineering Undergraduate Honors Theses

According to the CDC, nearly 800,000 individuals experience stroke each year in the United States [1]. Greater than 70% of strokes are of ischemic etiology and involve the occlusion of key arteries in the cardiovascular system [2]. Tissue plasminogen activator (IV-tPA) is the current gold standard for thrombolytic approaches [3]; however, this therapeutic is only effective between 3 and 4.5 hours from the patient’s last know well [4]. As a result, less than 5% of acute ischemic stroke patients receive IV-tPA. In order to increase the viability of AIS treatment as a whole, it is essential that thrombolytic techniques are …

The Influence Of Mmp14 On Angiogenesis In Chemotherapy-Treated Tumors, Abdussaboor Muhammad

Biomedical Engineering Undergraduate Honors Theses

Colorectal cancer is the third most common cancer in the world, and it is the fourth most common cause of cancer related death (1). There have been many significant advancements regarding the treatment of cancer which aim to shrink the size of tumors in patients. However, there is still more that needs to be understood about the many different factors that play a role in colorectal cancer development.

Angiogenesis is the process of forming new blood vessels from existing ones and it requires breaking down and remodeling of the extracellular matrix (ECM) in order to allow endothelial cells to migrate …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Design And Development Of Software With A Graphical User Interface To Display And Convert Multiple Microscopic Histology Images, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy

UNO Student Research and Creative Activity Fair

Histological images are widely used to assess the microscopic anatomy of biological tissues. Recent advancements in image analysis allow the identification of structural features on histological sections that can help advance medical device development, brain and cancer research, drug discovery, vascular mechanobiology, and many other fields. Histological slide scanners create images in SVS and TIFF formats that were designed to archive image blocks and high-resolution textual information. Because these formats were primarily intended for storage, they are often not compatible with conventional image analysis software and require conversion before they can be used in research. We have developed a user-friendly …

In Vitro Mitral Valve Model With Unrestricted Ventricular Access: Using Vacuum To Close The Valve And Enable Static Trans-Mitral Pressure, Sam E. Stephens, Alexander J. Kammien, Jacob C. Paris, Alexis P. Applequist, Neil B. Ingels, Hanna K. Jensen, Drew E. Rodgers, Charles R. Cole, Jonathan F. Wenk, Morten O. Jensen

Biomedical Engineering Faculty Publications and Presentations

Current in vitro models of the left heart establish the pressure difference required to close the mitral valve by sealing and pressurizing the ventricular side of the valve, limiting important access to the subvalvular apparatus. This paper describes and evaluates a system that establishes physiological pressure differences across the valve using vacuum on the atrial side. The subvalvular apparatus is open to atmospheric pressure and accessible by tools and sensors, establishing a novel technique for experimentation on atrioventricular valves. Porcine mitral valves were excised and closed by vacuum within the atrial chamber. Images were used to document and analyze closure …

Modulation Of Brain Tissue Transport And Endothelial Glycocalyx And Tight Junctions Of The Blood-Brain Barrier By Transcranial Direct Current Stimulation, Yifan Xia

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive approach to treat a broad range of brain disorders and to enhance memory and cognition in healthy individuals. In addition to directly acting on neurons by modulating the membrane potential, inducing neuronal polarization and changing cortical excitability in the brain to achieve its therapeutic effects, prior studies found that tDCS can transiently enhance the permeability (P) of the blood-brain barrier (BBB), the interface between blood circulation and brain tissue. Brain extracellular space (ECS) is a narrow microenvironment which surrounds every cell in the central nervous system (CNS). ECS occupies ~20% of brain …

Multimodal Ultrasound Imaging For Improved Metastatic Lymph Node Detection, Sidhartha Jandhyala

Dartmouth College Ph.D Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is complex in nature due to the variety of organs located in the head and neck region. Knowing the metastatic state of the lymph nodes is paramount in accurately staging and treating HNSCC patients. Currently, metastatic lymph node detection involves the use of magnetic resonance imaging and/or x-ray computed tomography, followed by biopsies for histological confirmation. The main diagnostic criteria is the size of the nodes; however, current imaging methods are not 100% accurate due natural lymph node variability. Ultrasound imaging is able to provide …

Diagnosis Of Melanoma Disease State From Patient Blood Samples Using Photoacoustic Flow Cytometry, Jacob Salvatore

Electronic Theses and Dissertations

Approximately 1 in 50 Americans develop melanoma in their lifetime. Early detection of melanoma is pivotal to the survival of the patient, with a 99% survival rate for 5 or more years after an early diagnosis. Metastasis, or the spread of cancer, increases the chances of cancerous growth in other parts of the body. In this study, we propose the use of photoacoustic flow cytometry as a diagnostic of patient disease state, by closely monitoring the amount of circulating melanoma cells (CMCs) in a patient’s blood before and after chemotherapy treatments. Using this patient data, we were able to make …

Developing Aligned Nerve Scaffolds In A 3d Type-I Collagen Gel, Gabriel David

Biomedical Engineering Undergraduate Honors Theses

Despite significant progress in the field of peripheral nerve repair, clinical success is still limited, leaving millions to suffer from peripheral neuropathy with billions spent every year for treatment. Nerve repair methods that are capable of maximizing the regenerative properties of peripheral nerves are greatly desired in the field of medical science. This research aims to fill the gap between modern methods and the future of nerve repair by creating type-I collagen scaffolds with aligned degradation pores that will assist and nurture nerves growing through them. This is achieved by incorporating adipose stem cells into type-I collagen hydrogels and aligning …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Bacteria Analysis By Using A Supervised Machine Learning Algorithm Based On Droplet Microfluidics, Yulder Daniel Angarita

Electronic Theses and Dissertations

Sepsis is a major medical problem and massive resources have been invested in developing and evaluating alternative treatments. Statistics indicate that sepsis causes between one third and one half of all hospital deaths in the United States. Sepsis has a high impact on health care in the US, with direct sepsis costs in 2009 exceeding $15.4 billion. A research study found that a 1-hour delay in appropriate antimicrobial care resulted in a 7% - 10% rise in mortality. Several professional societies seek to reduce sepsis mortality by targeting the timely use of diagnostic tests and antimicrobial therapy. The diagnostic instruments …