Biomedical Engineering and Bioengineering Commons^™

Bioengineered Scaffolds To Induce Alignment And Promote Axon Regeneration Following Spinal Cord Injury, Kiet Anh Tran

Theses and Dissertations

Scaffolds delivered to injured spinal cords to stimulate axon connectivity often act as a bridge to stimulate regeneration at the injured area, but current approaches lack the permissiveness, topology and mechanics to mimic host tissue properties. This dissertation focuses on bioengineering scaffolds through the means of altering topology in injectables and tuning mechanics in 3D-printed constructs as potential therapies for spinal cord injury repair. A self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunohistochemistry assays verify that vascularized peptide scaffolds promote axon infiltration, attenuate inflammation and reduce astrogliosis. Furthermore, …

Myosin Ii Adjusts Motility Properties And Regulates Force Production Based On Motor Environment, Omayma Y. Al Azzam, Janie C. Watts, Justin E. Reynolds, Juliana E. Davis, Dana N. Reinemann

Faculty and Student Publications

Introduction—Myosin II has been investigated with optical trapping, but single motor-filament assay arrangements are not reflective of the complex cellular environment. To understand how myosin interactions propagate up in scale to accomplish system force generation, we devised a novel actomyosin ensemble optical trapping assay that reflects the hierarchy and compliancy of a physiological environment and is modular for interrogating force effectors.

Methods—Hierarchical actomyosin bundles were formed in vitro. Fluorescent template and cargo actin filaments (AF) were assembled in a flow cell and bundled by myosin. Beads were added in the presence of ATP to bind the cargo AF …

Myosin Ii Adjusts Motility Properties And Regulates Force Production Based On Motor Environment, Omayma Alazzam, Janie Watts, Juliana Davis, Justin Reynolds, Dana N. Reinemann

Faculty and Student Publications

Introduction: Myosin II has been investigated with optical trapping, but single motor-filament assay arrangements are not reflective of the complex cellular environment. To understand how myosin interactions propagate up in scale to accomplish system force generation, we devised a novel actomyosin ensemble optical trapping assay that reflects the hierarchy and compliancy of a physiological environment and is modular for interrogating force effectors.

Methods: Hierarchical actomyosin bundles were formed in vitro. Fluorescent template and cargo actin filaments (AF) were assembled in a flow cell and bundled by myosin. Beads were added in the presence of ATP to bind the cargo AF …

Machine Learning And Scalable Informatics Methods To Predict Disease Status From Multimodal Biomedical Data, Hossein Mohammadian Foroushani

McKelvey School of Engineering Graduate Student Theses & Dissertations

Biological understanding of complex diseases such as stroke and obesity is critical for the advancement of medicine. Further knowledge discovery can provide effective biomarkers to improve disease diagnosis and prognosis, identify driver mutations, predict individual genetic susceptibility for early prevention and effective disease management, and facilitate development of personalized drugs. Stroke is the second leading cause of death and long-term disability in the world. Thus, stroke management is a time-sensitive emergency. The initial hours after stroke onset map the trajectory of subsequent neurologic complications. Cerebral edema develops hours to days after acute ischemic stroke and may result in midline shift …

Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …

Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiac arrhythmias, particularly ventricular arrhythmias, can be life-threatening and caused by both congenital genetic mutations and acquired cardiac injury. My thesis work was originally focused on delineating the effects of genetic mutation-driven dysregulation of a protein called Hey2 in Brugada Syndrome, a complex disease characterized by a predisposition to dangerous arrhythmias originating in the right ventricular outflow tract. In response to the pandemic, my thesis work shifted toward understanding the mechanisms of cardiovascular injury in Coronavirus disease 2019 (COVID-19), which is associated with serious cardiovascular complications, including ventricular arrhythmias and sudden cardiac death as well as endothelial dysfunction and coagulopathies. …

Imaging Techniques For Proton Range Determination In Proton Therapy, Xinyuan Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Proton therapy can achieve better sparing of normal tissues than the conventional photon radiation therapy due to proton’s Bragg Peak property. However, to unlock the full potential of protons, accurate prediction of in vivo proton stopping power ratio (SPR) is required for proton therapy treatment planning. The current standard practice is to map SPR from Hounsfield Unit (HU) values of a single-energy computed tomography (SECT) scan through a stoichiometric calibration technique. This technique is subjected to a variety of factors that congregate on the uncertainties in SPR estimation, including the calibration uncertainty (up to 0.5% to 1.8% of the total …

Measuring G Protein Activation With Spectrally Resolved Fluorescence Fluctuation Spectroscopy, Daniel Foust

McKelvey School of Engineering Graduate Student Theses & Dissertations

Fluorescence fluctuation spectroscopy (FFS) is comprised of a set of statistical techniques used to learn information about fluorescence particles by analyzing intensity fluctuations in signals detected from a fluorescence spectrometer or microscope. In biological contexts, FFS is commonly used to quantify the concentrations, molecular brightnesses, and transport properties (e.g. diffusion coefficients) of labeled biomolecules. In particular, the molecular brightness parameter is valuable because it can be used to quantify oligomerization of biomolecules. Therefore, FFS has emerged as an attractive tool for measuring protein-protein interactions in live cells. This dissertation describes the development of image-based, multicolor FFS techniques. Image-based FFS is …

Modeling The Effects Of Mechanical Loading On Hypertrophic Cardiomyopathy Pathogenesis In Human Induced Pluripotent Stem Cell Derived Micro Heart Muscle, Jingxuan Guo

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sudden cardiac death in the young is devastating. Advances in genetics have associated mutations in the contractile sarcomere apparatus of cardiomyocytes with hypertrophic cardiomyopathy, the most frequent cause of sudden cardiac death in the young. Currently, it is challenging to predict genotype-phenotype relationships in hypertrophic cardiomyopathy due to its incomplete disease penetrance. For example, different patients from the same family with identical genomic variants develop different symptoms. Non-genetic, environmental factors such as blood pressure are critical in heart function and disease. Therefore, understanding how mechanical factors contribute to phenotypes in diseases like hypertrophic cardiomyopathy is critical for developing effective therapeutics. …

Plasmonic Nanomaterials-Based Point-Of-Care Biosensors, Rohit Gupta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Point-of-care (POC) biosensors, although rapid and easy-to-use, are orders magnitude less sensitive than laboratory-based tests. Further they are plagued by poor stability of recognition element thus limiting its widespread applicability in resource-limited settings. Therefore, there is a critical need for realizing stable POC biosensors with sensitivity comparable to gold-standard laboratory-based tests. This challenge constitutes the fundamental basis of this dissertation work– to expand access to quality and accurate biodiagnostic tools. At the heart of these solutions lies plasmonic nanoparticles which exhibit unique optical properties which are attractive for label-free and labelled biosensors.Firstly, we improve the stability and applicability of label-free …

Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros

McKelvey School of Engineering Graduate Student Theses & Dissertations

Proton radiotherapy has the potential to treat tumors with better conformal dose distribution than competing modalities when the rapid dose falloff at the end of the proton-beam range is correctly aligned to the edge of the clinical target volume (CTV). However, its clinical potential is dependent on the accurate localization of the Bragg-peak position from predicted stopping-power ratio maps. The method that is most commonly used in today’s clinical practice for predicting stopping-power ratio (SPR) consists of a stoichiometric calibrationtechnique based on single-energy CT (SECT) for direct estimation of patient-specific SPR distribution from vendor-reconstructed Hounsfield Unit (HU) images. Unfortunately, this …

Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Neuromodulation technology is key to understanding brain function and treating brain diseases. Conventional neuromodulation technologies, such as direct current stimulation, transcranial magnetic stimulation, and optogenetics, predominately rely on electromagnetic waves. However, the fundamental physical law  the tradeoff-relationship between penetration and spatial resolution, limits their transcranial penetration within the superficial cortex layer. To overcome this challenge, electrodes or optical fibers need to be surgically implanted into the brain to modulate specific brain regions. Different from electromagnetic waves, ultrasound, as a mechanical wave, can non-invasively penetrate through the intact skull to reach deep brain regions with millimeter spatial focus. Ultrasound has …

Ligand- And Strain-Specific Control Of Microbial Communities, Austin Grant Rottinghaus

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes naturally coexist in complex, multi-strain communities that are valuable assets for their host. Commensal and probiotic microbes prevent pathogen colonization, reduce the frequency and severity of various ailments, provide essential nutrients, and offer various additional benefits. Understanding the dynamics of and tailoring microbial communities to provide additional beneficial functions is a primary focus of researchers in medicine and agriculture. To date, consortia have primarily been manipulated by supplementing the communities with microbes that were engineered in vitro or by introducing stimuli that alter the metabolism or composition of the community. This method has proven successful, with numerous microbes engineered …

Pet/Mr Imaging Biomarkers For Cerebral Small Vascular Diseases: Tissue Oxygenation Stress And Neuroinflammation, Chunwei Ying

McKelvey School of Engineering Graduate Student Theses & Dissertations

Fifty million people are affected by dementia worldwide. Cerebral small vessel disease (CSVD) often leads to vascular contributions to cognitive impairment and dementia (VCID), the second leading cause of dementia after Alzheimer’s disease (AD), accounting for up to 45% of dementia. White matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) imaging and disrupted white matter microstructure on diffusion tensor imaging (DTI) have been widely used as biomarkers to evaluate CSVD.

The pathogenesis underlying CSVD is not well understood. It has been postulated that exposure to risk factors, including hypertension, diabetes, and smoking over years injures small arterioles, impairs autoregulation and …

Focused Ultrasound-Enabled Blood-Based Liquid Biopsy (Sonobiopsy) For Brain Disease Diagnosis, Christopher Pham Pacia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Brain cancer severely threatens human health due to its disruption of neurological function, poor prognosis, and substantial reduction in quality of life. Glioblastoma (GBM) is the most devastating brain cancer; not only is it the most common malignant primary tumor in adults, but also it has a median survival of 14 months with a 5-year survival rate of less than 5%. Despite advances in multidisciplinary treatment that includes surgical resection, radiation therapy, and chemotherapy, almost all patients experience tumor progression and nearly universal mortality within 2 years. However, advances in patient care have suggested that the accurate diagnosis of molecular …

Fast And Radiation-Free High-Resolution Mr Cranial Bone Imaging For Pediatric Patients, Parna Eshraghi Boroojeni

McKelvey School of Engineering Graduate Student Theses & Dissertations

AbstractEach year, 2.2 million pediatric head computed tomography (CT) scans are performed in the United States. Head trauma and craniosynostosis are two of the most common pediatric conditions requiring head CT scans. Head trauma is common in children and one-third of the patients that present to the emergency room undergoes head CT imaging. Craniosynostosis is a congenital disability defined by a prematurely fused cranial suture. Standard clinical care for pediatric patients with head trauma or craniosynostosis uses high-resolution head CT to identify cranial fractures or cranial sutures. Unfortunately, the ionizing radiation of CT imaging imposes a risk to patients, particularly …

Development Of The Assessment Of Clinical Prediction Model Transportability (Apt) Checklist, Sean Chonghwan Yu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Clinical Prediction Models (CPM) have long been used for Clinical Decision Support (CDS) initially based on simple clinical scoring systems, and increasingly based on complex machine learning models relying on large-scale Electronic Health Record (EHR) data. External implementation – or the application of CPMs on sites where it was not originally developed – is valuable as it reduces the need for redundant de novo CPM development, enables CPM usage by low resource organizations, facilitates external validation studies, and encourages collaborative development of CPMs. Further, adoption of externally developed CPMs has been facilitated by ongoing interoperability efforts in standards, policy, and …

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …

Advancing The Portability, Field Of View, And Spatiotemporal Resolution Of Multi-Parametric Photoacoustic Microscopy, Fenghe Zhong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Capable of structural, functional, molecular, and metabolic imaging with high spatial resolution in vivo, photoacoustic microscopy (PAM) is an emerging tool in biomedical research. Further, recent advances in multi-parametric acquisition and analysis make PAM uniquely capable of simultaneously mapping the total concentration of hemoglobin (CHb), oxygen saturation of hemoglobin (sO2), and blood flow speed. However, there are multiple major limitations, including, the large footprint, low imaging speed, limited imaging contrast, and insufficient axial resolution, which impedance its applications in basic and translational research. In this dissertation, I presented potential solutions to overcome the limitations above.In the first part of this …

Thermomagnetic-Responsive Self-Folding Microgrippers For Improving Minimally Invasive Surgical Techniques And Biopsies, Caleigh R. Dunn, Bruce Lee, Rupak Rajachar

Michigan Tech Publications, Part 1

Traditional open surgery complications are typically due to trauma caused by accessing the procedural site rather than the procedure itself. Minimally invasive surgery allows for fewer complications as microdevices operate through small incisions or natural orifices. However, current minimally invasive tools typically have restricted maneuverability, accessibility, and positional control of microdevices. Thermomagnetic-responsive microgrippers are microscopic multi-fingered devices that respond to temperature changes due to the presence of thermal-responsive polymers. Polymeric devices, made of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and polypropylene fumarate (PPF), self-fold due to swelling and contracting of the hydrogel layer. In comparison, soft metallic devices feature a pre-stressed metal bilayer …