Molecular, Cellular, and Tissue Engineering Commons^™

Modeling Epithelial-Mesenchymal Transition In A 3d Multicellular Model Of Tgf-Β1 Signaling, Kristin Kim, Chris Lemmon

Biology and Medicine Through Mathematics Conference

No abstract provided.

A Novel Mrna Delivery Strategy Employing Adenovirus Piggyback Mrna Binders Via Catcher/Tag Molecular Glue, Kexin Geng

McKelvey School of Engineering Graduate Student Theses & Dissertations

mRNA-based therapeutics open a new era for the prevention and treatment of a wide range of diseases. However, existing mRNA delivery vehicles have limited repertoires for dendritic cell targeting and intranasal administration which are two paramount delivery pathways of significant advantages for treating cancer and infectious respiratory diseases. Adenovirus (Ad) with well-deciphered viral genomes and intensive-studied structure biology has been developed for DCs-targeted cancer vaccines and intranasal COVID vaccines. In light of these virtues, Ad presents as the “off-the-shelf” tool possessing well-defined manufacturable capabilities and translatable feasibility that perfectly complements the current limitations of mRNA delivery. In this study, we …

The Development Of A Primer Payload With Microparticles For Uti Pathogen Identification Using Polythymidine- Modified Lamp Primers In Droplet Lamp, Jonas Otoo

KGI Theses and Dissertations

Nucleic acid amplification tests (NAATs) are among the diagnostic tests with the highest sensitivity and specificity. However, they are more complex to develop than other diagnostic tests such as biochemical tests and lateral flow immunoassay tests. Polymerase chain reaction (PCR) is the gold standard for NAATs. PCR requires thermal cycling to achieve clonal amplification of the target pathogen DNA for diagnosis. Thermal cycling poses a challenge in the development of PCR diagnostics for point-of-care (POC) settings. Loop-mediated isothermal amplification (LAMP) offers an isothermal method for NAATs diagnostics. The advancement of the microfluidics field significantly enhances the development of LAMP diagnostics …

Understanding Vascular Calcification Through The Lens Of Canonical Wnt Signaling, Karlee Mcneel

Theses and Dissertations

Every 37 seconds, someone in the United States dies from cardiovascular disease. Vascular calcification is one of the underlying causes of these fatal events. Medial calcification develops following arteriosclerosis, or hardening of the arteries. Medial calcification is characterized by the deposition of hydroxyapatite in the medial layer of the arteries after normal vascular smooth muscle cells undergo a phenotypic switch to resemble osteoblast-like cells. It is hypothesized that this switch is caused by the wingless related (WNT)-Signaling pathway. The WNT-Signaling pathway, upon activation, causes the upregulation of osteogenic markers for the development of osteoblast-like cells. Current treatments alleviate consequences of …

Growth Plate Cartilage: Understanding The Contribution Of Adhesion To Column Formation And Matrix Structure, Sydney E. Greer

Theses & Dissertations

Throughout fetal and adolescent development, bone growth is regulated by fine-tuned and controlled maturation of chondrocytes through a cartilaginous template called the growth plate. Bone growth rate is controlled through cell enlargement and extracellular matrix deposition, while the polarized arrangement of proliferative chondrocytes into columns aligned with the long axis of the bone potentiate growth. Chondrocytes are surrounded by a complex three-dimensional arrangement of matrix molecules, all of which are secreted by chondrocytes and assembled/remodeled to support the biological functions of the cell. Adhesion receptors found on the cell membrane of chondrocytes are crucial to the organization of matrix proteins …

Implementation Of Methods For Cell Therapy Research And Assessment Of The Impact Of Cryopreservation, Samantha Lynes

Master's Theses

Cell therapy is the administration of living cells into a patient to prevent or treat a variety of diseases and illnesses. The cell therapy industry is rapidly expanding, and continued research is necessary for manufacturing safe and effective therapies. Although cell therapy manufacturing generally involves cryopreservation processes for storage, there are limited standards for cryopreservation processes and assays required to evaluate cell therapies post-thaw, and limited understanding exists about how a recovery period post-thaw could impact cell health. The overall goal of this thesis was to evaluate the effect of cryopreservation and potential subsequent recovery time on cell viability.

Because …

Assesment Of Structure, Function, And Microevolutionary Dynamics Of Extrachromosomal Circular Dna In Chinese Hamster Ovary Cells, Dylan Chitwood

All Dissertations

Chinese hamster ovary (CHO) cell lines are among the most popular expression hosts used in biopharmaceutical manufacturing due to relative ease of culture, capacity to perform human-like post-translational modifications, and non-susceptibility to viruses. However, the intrinsic plasticity of the CHO genome can lead to undesired genetic rearrangements, phenotypic shifts, reduced product quality, and early culture termination that prevents continuous biomanufacturing. A characteristic of plastic and unstable genomes that is poorly understood in CHO cells is extrachromosomal circular DNA (eccDNA). EccDNAs are focal amplifications of the genome that reside in the extranuclear space. These plasmid-like entities are structurally complex and are …

Investigating The Effect Of Pancreatic Cancer Tumor-Derived Extracellular Vesicles On Schwann Cell Activation, Isabel Powers

Biomedical Engineering Undergraduate Honors Theses

Pancreatic cancer is one of the deadliest diseases because it is hard to identify in its early stages, has high chemoresistance, and early metastasis. Because of these traits, it is often associated with perineural invasion (PNI), where the cancer travels to the nervous system. Schwann cells (SC) are associated with both metastasis and PNI when activated. The purpose of this study was to determine if and how pancreatic tumor-derived extracellular vesicles (TEVs) can activate SC in PNI. This experiment was performed by embedding Schwann cells in a hydrogel to model the tumor microenvironment and treating them with isolated extracellular vesicles …

Optimizing Three-Dimensional Bioengineered Co-Cultures For The Study Of Fibrotic Spinal Cord Injury, Sarah Aly

Biomedical Engineering Undergraduate Honors Theses

Spinal cord injuries (SCIs) have major physical implications on those affected^[1]. There are two main types of scarring that occur after injury; they are known as the glial and fibrotic scar. The injured site causes an altered micro-environment which transforms astrocytes from their normal to reactive state, thus inhibiting axonal regeneration. The effect of reactive astrocytes on fibrotic scarring is not fully understood due to limited study^[2,3]. Using Three-Dimensional (3D) bioengineered co-cultures of astrocytes and neuroblasts the pathological environment can be replicated and manipulated to further the study of fibrotic scarring. Temperature casted co-cultures were successfully …

Exploring The Effects Of Microarchitecture On Astrocyte Behavior And Vascular Remodeling In Spinal Cord Injury, Devin Gerber

Biomedical Engineering Undergraduate Honors Theses

Spinal cord injury (SCI) is a common condition and is characterized by traumatic and progressive damage that results in limited neuron regeneration and thus a restricted recovery. In SCI, the vasculature is also severely damaged, which exacerbates inflammation at the injury site. Specifically, insufficient angiogenesis occurs at the site of injury due to the fibrotic pathological microenvironment1 . SCI also leads to the formation of a fluid-filled cavity and thus gliosis and fibrosis, forming a dense glial and fibrotic scar around the cavity. The microenvironment at the injury site plays a significant role in astrocyte behavior, promoting the transformation of …

Study Of The Stability Of Heparin/Collagen Layer-By-Layer Coatings, Hector M. Apodaca Reyes

Chemical Engineering Undergraduate Honors Theses

Pairing heparin with collagen-based medical implants has opened a whole new area of research for enhancing the desired effect of current implants. In fact, heparin (HEP) and collagen (COL) layer-by-layer (LbL) coatings have shown impressive results in forming polyelectrolyte multilayers. It has been already seen on skin grafts, nerve guide conduits (NGCs), and drug delivery devices yielding promising results. Due to being a simple, cost-efficient, and versatile option to fabricate thin biomimetic films, this self-assembly technique is one of the most effective methods to immobilize extracellular matrix (collagen and heparin) onto medical devices and implants. Even though previous studies have …

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 …

A Magneto-Rheological Platform To Dynamically Control Afterload In Engineered Micro Heart Muscles, David Schuftan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiovascular disease is the leading cause of death is the United States, accounting for nearly 1 in 5 deaths. Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, how these mechanical forces exactly affect the cellular biology of the heart is not well defined. In vitro models using cardiomyocytes derived from human induced pluripotent stem cells enable researchers to develop medium throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces such as cardiac afterload. However, most of these models require …

Comprehensive Long- And Short- Read Sequencing Approaches To Screen The Mutational Landscape After Therapeutic Crispr-Editing For Duchenne Muscular Dystrophy, Mary Jia, Made Harumi Padmaswari, Landon Burcham, Shilpi Agrawal, Alexis Ivy, Abbey Bryan, Christopher E. Nelson

Biomedical Engineering Undergraduate Honors Theses

Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease caused by mutations in the Dmd gene resulting in non-functional dystrophin. Adeno-associated virus (AAV)-mediated delivery of classical CRISPR systems resulting in double-stranded breaks (DSBs) has yielded promise as a curative DMD therapeutic. However, the consequences of AAV-CRISPR require more thorough characterization. PCR-enriched short-read amplicon sequencing at cut sites is the most common method of sequencing CRISPR editing, but PCR bias results in unreliable quantification of on-target edits. We analyze orthogonal long- and short-read sequencing approaches to screen the outcomes of CRISPR technologies at the DNA and RNA-level for DMD. We …

Tumor Targeting Gold Nanoparticles For Delivery Of Rna And Dna Oligonucleotide Therapies For Glioblastoma., Nicholas Allen

Electronic Theses and Dissertations

Glioblastoma (GBM) brain tumors are highly aggressive gliomas due to genetic and cellular heterogeneity. Current GBM treatment consists of surgical resection of the tumor combined with radio- or chemo-therapies. While these treatments have increased the life expectancy for GBM patients up to 20 months, they have had little effect on the 5-year survival rate. The complex cellular and genetic composition of the tumor makes current treatments less effective long term. One approach to developing more effective GBM treatments is to customize nanoparticle-based drug delivery systems that can directly target the aberrant gene expression patterns within a particular GBM tumor. Delivery …

Dpd Guided Insight On The Formation Process Of Polyethersulfone Membranes By Nonsolvent Induced Phase Separation And The Effects Of Additives, Eric Ledieu

Graduate Theses and Dissertations

Dissipative particle dynamics (DPD), a coarse grain simulation method, was applied to the membrane formation process of non-solvent induced phase separation (NIPS) to gain further insight on the mechanism of certain variables and how they affect the final morphology. NIPS involves two solutions, an organic polymer dissolved in an organic solvent colloquially called the dope and an aqueous coagulation bath, brought into contact with one another. The solvents then mix, causing the polymer to fall out of solution as an asymmetric membrane with a dense surface layer and a more open subsurface layer in response to the decreasing solubility. Polyethersulfone …

Effect Of Human Decellularized Skeletal Muscle On Recovery From Volumetric Muscle Loss Injury, Jacob Schluns

Graduate Theses and Dissertations

Volumetric muscle loss (VML) overwhelms muscle’s robust capacity for regeneration. A key event in the etiology of VML injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). While muscle is a highly structured tissue, with cell and ECM alignment in the direction of contractile force production, the impact of scaffold alignment on recovery remains unclear. Bulk human decellularized skeletal muscle (DSM) tissues were sectioned into 10 x 1-2 mm fibers. VML defects were repaired using multi-fiber implants consisting of approximately 8 fibers per defect arranged into two layers. Fibers were oriented 1) to the …

Preparing Homogenous Composites Of Collagen And Cellulose Nanocrystals For Tissue Engineering Research, Zachary Stanley

Biological and Agricultural Engineering Undergraduate Honors Theses

Advancements in medicine and our understanding of stem cells have led to a greater emphasis on further developing research focused on tissue engineering. This research has led to the rise of both two-dimensional and three-dimensional scaffolds that can be utilized to repair bone, skin, vascular, and potentially even nervous tissue. One of the prominent compounds used in modern scaffolds is collagen-based hydrogels due to their low antigenicity and ability to provide structure to cells. There is potential to further improve upon this three-dimensional scaffold by incorporating cellulose nanocrystals (CNCs) into a composite hydrogel with collagen. The addition would increase the …

Polymeric Biomaterials Approaches For Engineering The In Vitro Cellular Microenvironment For Mscs, Mahsa Letter-Mahsa Haseli

Graduate Theses and Dissertations

Cell therapy is a technology that relies on replacing diseased or dysfunctional cells with healthy functioning ones. One of the cells used for such advanced therapies are stem cells, owing to their ability to differentiate into specific cells required for repairing damaged or defective tissues or cells. The majority of cell-based products are intended to transiently persist in the patient, secreting factors which then allow the patient’s body to heal; in these products, the cells are subsequently eliminated from the body. Furthermore, unique manufacturing platforms, in addition to novel commercialization strategies, will be required to create a successful, sustainable cell …

Regenerative Medicine For Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation And Application, Takashi Taguchi

LSU Doctoral Dissertations

Tendon and ligament injuries are debilitating conditions across species. Poor regenerative capacities of these tissues limit restoration of original functions. The first study evaluated the effect of cellular administration on tendon/ligament injuries in horses using meta-analysis. The cellular administration was effective in restoring ultrasonographic echogenicity and increasing vascularity during early phase of healing. Additionally, it improved microstructural organization of healed tissue in terms of cellularity and fiber alignment. However, the study did not support its use for increasing rate of return to performance, expression/deposition of tendon-specific genes/proteins, or mechanical properties.

The findings led to the second study that engineered implantable …