Molecular, Cellular, and Tissue Engineering Commons^™

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 …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Computational Modeling Using A Novel Continuum Approach Coupled With Pathway-Informed Neural Networks To Optimize Dynein-Mediated Centrosome Positioning In Polarized Cells, Arkaprovo Ghosal, Padmanabhan Seshaiyar Dr., Adriana Dawes Dr., General Genomics Inc.

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Physiologically Relevant Fluid Shear Stress Induced Receptor Conversion In Hormone Receptor-Positive (Hr+) Breast Cancer, Jonathan James Cuccia

LSU Doctoral Dissertations

Breast cancer is the most common type of cancer among all people in the United States as of 2023 and often has devastating impacts on afflicted patients. Although some treatments show great efficacy against primary breast tumors, none have been able to significantly reduce the mortality rate of breast cancer once it has metastasized to distant sites. In primary, hormone receptor-positive (HR+) breast cancers, endocrine therapies are often used as first-line treatments and are generally well-tolerated. However, as the disease progresses, these previously sensitive cancers can become resistant to endocrine therapies and continue proliferating despite them. Therefore, there is a …

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 …

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 …

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 …

Local Il-10 Delivery Modulates The Immune Response And Enhances Repair Of Volumetric Muscle Loss Muscle Injury, Tai Huynh, Cassandra Reed, Zain Blackwell, Peyton Phelps, Luis Carlos Pinzon-Herrera, Jorge Almodovar, David A. Zaharoff, Jeffery Wolchok

Biomedical Engineering Faculty Publications and Presentations

This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling as a promising immunotherapeutic target. To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in rats using autologous minced muscle (MM). Animals received either recombinant rat IL-10 or phosphate buffered saline (PBS) controls injections at the site of VML repair beginning 7 days post injury (DPI) and continuing …

Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna

Theses and Dissertations--Chemical and Materials Engineering

Volumetric muscle loss (VML) remains one of the few skeletal muscle injuries without a reliable and repeatable treatment. In large volume muscle injuries, muscle fibers as well as the surrounding connective tissue are damaged, preventing therapeutic muscle stem cells, called myogenic progenitor cells (MPCs), from reaching the injury site and initiating repair. There is a clinical need to rapidly fabricate in vitro muscle tissue constructs that mimic the native tissue organization, with aligned myotubes, for insertion and integration at the patient’s injury site. In this dissertation, we utilize the MPC’s natural propensity to close gaps across an injury site to …

Enhancing Human Schwann Cells Reparative Behavior Using Heparin/Collagen Layer-By-Layer Coatings, Luis Carlos Pinzon-Herrera

Graduate Theses and Dissertations

When a peripheral nerve injury (PNI) occurs, the gold standard for tissue regeneration is the use of autografts. However, due to the secondary effects produced by multiple surgeries involved in the removal and implantation of autografts for very small lesions, it is possible to replace them with the use of Nerve Guide Conduits (NGCs). However, NGCs are limited to short lesions (less than 1 cm). This limitation is caused by the absence of compounds in the extracellular matrix (ECM) that autografts can provide. Since much of the regenerative process takes place on the NGC surface, our work aims to modify …

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …

Isolation And Production Of Tandem Collagen Binding Domain From Clostridial Collagenase Colg And Developments In C1q Reagent Production For Future Molecule Characterization Work, Stephanie Beitle

Chemical Engineering Undergraduate Honors Theses

This thesis covers a two part project: the production methods to create a double collagen binding domain molecule with a growth factor for wound healing applications and the development of a new in-house production method for isolating C1q from bovine blood. The wound healing molecule was created using transformation, sonication, and purification before being tested via electrophoresis SDS page and Western blots to confirm the molecule’s presence. The C1q in-house production method utilizes an ultrafiltration flow cell rather than dialysis at a critical point in the process, allowing for researchers to not only be able to use a single small …

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 …

Heparan Sulfate Proteoglycan Glypican‑1 And Pecam‑1 Cooperate In Shear‑Induced Endothelial Nitric Oxide Production, Anne Marie W. Bartosch, Rick Mathews, Marwa M. Mahmoud, Limary M. Cancel, Zahin S. Haq, John M. Tarbell

Publications and Research

This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress …

Development Of An Integrated Salt Cartridge-Reverse Electrodialysis (Red) Device To Increase Electrolyte Concentrations Of Human Blood Flow To Power Biomedical Devices, Caroline Campbell

Chemical Engineering Undergraduate Honors Theses

Emerging technologies in nanotechnology and biomedical sciences have led to an increase in biomedical implantable devices including cardiac pacemakers, artificial organs, drug pumps, and sensors. These devices require continuous stable and reliable power to operate, which creates the demand for the need to find a safe, reliable, and stable power source. A promising avenue for a power source for these devices is a miniaturized reverse electrodialysis (RED) biopower cell design that utilizes the salinity differences between bloodstreams that flow inside the human body. Initial results of the RED system demonstrate that higher gradient salinity differences between streams lead to a …

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 …

Quantifying Mafenide Release From 3d Printed Phenylalanine-Coumarin Copolyester Scaffolds, Jacob Seeh

Williams Honors College, Honors Research Projects

This project addressed burn wound healing through controlled release of the antibacterial drug mafenide encapsulated by a copolyster into 3D printed scaffolds. Scaffolds were printed at 25^oC and 0.77-1 bar in a cross-hatch pattern with uniform thickness, distance between parallel layers, and diameter then photo-crosslinked. The number of scaffolds available for testing was limited by the amount of polymer that could be synthesized. A high-performance liquid chromatography method was developed specifically for this experiment and used to determine daily release of mafenide from the scaffold into a 2-mL phosphate buffer solution. During the first 24 hours a large …

Optimization Of Gelatin-Based Cellular Coating Of Msc For Myocardial Infarction Therapy, Kara Amelle Davis

Theses and Dissertations--Chemical and Materials Engineering

Cardiovascular disease remains the number one threat to American lives. During an acute myocardial infarction (AMI), blood flow is blocked and results in the formation of scar tissue. As the body’s immune system responds, inflammatory signaling causes an increase in both scar tissue size and the patient’s risk for further chronic heart failure. In order to reduce the risk of continued heart disease inflammatory signaling must be reduced. Stem cell therapies have the ability to alter the immune system’s pro-inflammatory signal. However, stem cell retention is limited due to blood flow shear. Gelatin methacrylate (GelMA) based coatings have been shown …

Incorporation Of Lignin In Natural And Synthetic Biomaterials To Alter Mechanical And Biochemical Properties For Enhanced Wound Healing, Jorge Alfonso Belgodere

LSU Doctoral Dissertations

It is estimated that chronic, non-healing wounds affect more than 6.5 million Americans annually, with an estimated healthcare cost beyond $14 billion. Here, we attempted to create composites of natural (collagen type I or gelatin-methacrylate) or synthetic (poly(ethylene glycol) polymers incorporating a natural plant component, lignin, to combat the costs and limitations current wound healing methods face. Three-dimensional matrices of collagen type I (Col I) are widely used in tissue engineering applications for its abundance in many tissues, bioactivity with many cell types, and excellent biocompatibility. Inspired by the structural role of lignin in plant tissue, we found that sodium …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Graduate Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation …

Bioproduction Of Adipic Acid Using Engineered Pseudomonas Putida Kt2440 From Lignin-Derived Aromatics, Howard Willett

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Current industrial synthesis of adipic acid is nonrenewable and depends on a carcinogenic starting material, benzene. Biocatalysis with an engineered microorganism could turn a renewable feedstock into a value-added chemical such as adipic acid. Here we engineered P. putida KT2440 to transform lignin-derived aromatics, coumarate and ferulate, into adipic acid. Lignin is a recalcitrant plant biopolymer burned for thermal energy. Conversion of lignin into a value-added chemical will improve the efficiency of lignocellulose processing plants. The best performing engineered KT2440 strain produces 2.52 mM adipate at a 9.5% (mole/mole) yield. This was achieved by the genetic insertion of non-natural biosynthetic …

Modification Of Lipid Microenvironments On Solid Support Structures For Use In Transmembrane Protein Assays, William J. Houlihan

Dissertations and Theses

Gamma-Secretase (γ-secretase) is a transmembrane protease of increasing interest, which has been shown to have significant connections to both cancer and Alzheimer’s disease. γ-secretase cleaves both Notch-1, a transmembrane signaling protein, and Amyloid precursor protein (APP), a transmembrane protein whose cleavage may result in the formation of β-amyloid plaques in the brain. Notch-1 and APP are widely studied proteins that have substantial impacts on the development and proliferation of cancer and Alzheimer’s disease, respectively. Notch-1 partakes in the signaling of apoptosis in damaged and mutated cells, thus its cleavage by γ-secretase within the plasma membrane has ramifications on cell growth …

Cell Surface Coatings For Mammalian Cell-Based Therapeutic Delivery, Pei-Jung Wu

Theses and Dissertations--Chemical and Materials Engineering

The cell plasma membrane is an interactive interface playing an important role in regulating cell-to-cell, cell-to-tissue contact, and cell-to-environment responses. This environment-responsive phospholipid layer consisting of multiple dynamically balanced macromolecules, such as membrane proteins, carbohydrate and lipids, is regarded as a promising platform for various surface engineering strategies. Through different chemical modification routes, we are able to incorporate various artificial materials into the cell surface for biomedical applications in small molecule and cellular therapeutics.

In this dissertation, we establish two different cell coating techniques for applications of cell-mediated drug delivery and the localization of cell-based therapies to specific tissues. The …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

Molded Features In Pdms For Fabricating Bacterial Cellulose For Various Geometries, Mitchell Habegger

Williams Honors College, Honors Research Projects

The purpose of producing features on bacterial cellulose (BC) is to facilitate the elongation and alignment for cells, in this case Normal Human Dermal Fibroblast (NHDF) cells. The elongated cells have applications in wound healing, tissue engineering, disease diagnostics, and many other fields. Experiments were run to test the effectiveness of transferring features to BC sheets from features induced by fracturing on polydimethylsiloxane (PDMS) and those duplicated from molds with existing features. The features were duplicated to BC sheets by either air drying or Guided Assembly-Based Biolithography (GAB). The research results showed that fracture inducing on PDMS produced very small …

Reducing Biomass Recalcitrance By Heterologous Expression Of A Bacterial Peroxidase In Tobacco (Nicotiana Benthamiana), Ayalew Ligaba-Osena, Bertrand Hankoua, Kay Dimarco, Robert Pace, Mark Crocker, Jesse Mcatee, Nivedita Nagachar, Ming Tien, Tom L. Richard

Center for Applied Energy Research Faculty and Staff Publications

Commercial scale production of biofuels from lignocellulosic feed stocks has been hampered by the resistance of plant cell walls to enzymatic conversion, primarily owing to lignin. This study investigated whether DypB, the lignin-degrading peroxidase from Rodococcus jostii, depolymerizes lignin and reduces recalcitrance in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the cytosol or the ER using ER-targeting and retention signal peptides. For each construct, five independent transgenic lines were characterized phenotypically and genotypically. Our findings reveal that expression of DypB in the cytosol and ER does not affect plant development. ER-targeting increased protein accumulation, and …