Molecular, Cellular, and Tissue Engineering Commons^™

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 …

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 …

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 …

Metabolomic Differentiation Of Tumor Core And Edge In Glioma., Mary E. Baxter

Electronic Theses and Dissertations

Glioma is one of the most aggressive forms of brain cancer. It has been shown that the microenvironments differ significantly between the core and edge regions of glioma tumors. This study obtained metabolomic profiles of glioma core and edge regions using paired glioma core and edge tissue samples from 27 human patients. Data was acquired by performing liquid-liquid metabolite extraction and 2DLC-MS/MS on the tissue samples. In addition, a boosted generalized linear machine learning model was employed to predict the metabolomic profiles associated with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

A panel of 66 metabolites was found to be statistically significant …

Decellularized Heart Extracellular Matrix As A Biomimetic Substrate For Alleviating Hipsc-Cardiac Fibroblast Activation And Enhancing Isogenic Cardiac Organoids, Charles Kerr

MUSC Theses and Dissertations

Cardiovascular disease is the constant leading cause of death worldwide. While substantial efforts have been undertaken to improve disease outcomes, the lack of adequate human cardiac tissue models exacerbates research and development costs and clinical trial failures, hampering novel therapeutic discovery. To address this, human engineered cardiac microtissues composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) show potential in recapitulating hallmark qualities of natural human myocardium for novel therapeutic testing, disease modeling and cardiotoxicity screening. However, as these models are engineered in vitro, they are limited in their capacity to fully recapitulate myocardium and are vulnerable to influences …

Histological Evidence For The Therapeutic Effect Of Chitosan Nanofibrous Dressing On Acute Skin Wounds In A Rat Model, Mahboubeh Ghanbari, Sayed Ahmadreza Razian, Sara Cartwright, Yury Salkovskiy, Jason Mactaggart, Mark A. Carlson

UNO Student Research and Creative Activity Fair

Introduction: Large-area skin traumas, such as thermal burns, are among the most severe health issues that decrease patients’ quality of life and burden healthcare systems. The CDC estimates that there are 1.1 million burns requiring medical attention each year, with more than 20,000 cases involving at least 25% of the body surface, resulting in 4,500 deaths. In addition, about 10,000 people die from burn-related infections. A promising solution to alleviate this problem is using wound dressings based on biopolymers with inherent wound healing properties and biodegradability. One of these biopolymers is chitosan, which is derived from arthropod shells and exhibits …

The Effects Of Demographics And Risk Factors On The Morphological Characteristics Of Human Femoropopliteal Arteries, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy

UNO Student Research and Creative Activity Fair

Background: Disease of the lower extremity arteries (Peripheral Arterial Disease, PAD) is associated with high morbidity and mortality. During disease development, the arteries adapt by changing their diameter, wall thickness, and residual deformations, but the effects of demographics and risk factors on this process are not clear.

Methods: Superficial femoral arteries from 736 subjects (505 male, 231 female, 12 to 99 years old, average age 51±17.8 years) and the associated demographic and risk factor variables were used to construct machine learning (ML) regression models that predicted morphological characteristics (diameter, wall thickness, and longitudinal opening angle resulting from the …

Effects Of Post-Translational Histone Modifications On Transcription Rate, Aaron Bohn

Annual Research Symposium

No abstract provided.

Development Of A Porous Layer-By-Layer Microsphere With Branched Aliphatic Hydrocarbon Porogens, Farah Shahjin, Milankumar Patel, Mahmudul Hasan, Jacob D. Cohen, Farhana Islam, Md Ashaduzzaman, Mohammad Ullah Nayan, Mahadevan Subramaniam, You Zhou, Irene Andreu, Howard E. Gendelman, Bhavesh D. Kevadiya

Nebraska Center for Biotechnology: Faculty and Staff Publications

Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms.

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 …

Expression Optimization Of The Gst-Gfp Fusion Protein Through The Alteration Of Induction Conditions, Matthew J. Vaccaro

Honors Undergraduate Theses

This research sought to determine which induction condition resulted in the greatest GST-GFP fusion protein expression. It will hopefully serve as a guide for future researchers trying to produce their own recombinant protein containing GST and GFP-tags. The CDNB Enzyme Assay was used to determine the quantity of GST-GFP fusion protein present and tested three variables: IPTG concentration, duration, and temperature of induction. The findings showed that IPTG concentration, temperature, and induction duration all had a significant impact on protein expression. Induction temperatures of 20 °C and 25 °C showed better protein expression at IPTG concentrations of 1.0 mM IPTG …

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods

Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …

Telp Theory: Elucidating The Major Observations Of Rieger Et Al. 2021 In Mitochondria, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons (TELP) theory may represent a complementary development to Mitchell's chemiosmotic theory. The combination of the two together can now excellently explain the energetics in mitochondria. Our calculated transmembrane-attractive force between an excess proton and an excess hydroxide explains how TELP may stay within a 1-nm thin layer at the liquid-membrane interface. Consequently, any pH sensor (sEcGFP) located at least 2–3 nm away from the membrane surface will not be able to see TELP. This feature as predicted from the TELP model was observed exactly in the experiment of Rieger et al., 2021. In contrast to their …

3-Dimensional Muscle Constructs: Using Hydrogels In Order To Model The Effects Of Exercise In Disease Conditions, Mark Mchargue

Theses and Dissertations--Biomedical Engineering

Currently, there is no standard in vitro model for studying the effects of mechanical stimulation on muscle in type II diabetes. Existing models primarily utilize electrical stimulation, which does not fully recapitulate the effects of exercise. In this thesis, we create a standardized in vitro model of murine muscle that can recapitulate the benefits seen in exercise when mechanically stimulated. Moreover, we show that a type II diabetes environment has similar effects on the muscle in vitro as well as in vivo.

Fusarium Graminearum Effector Fgnls1 Targets Plant Nuclei To Induce Wheat Head Blight, Guixia Hao, Todd A. Naumann, Hui Chen, Guihua Bai, Susan Mccormick, Hye-Seon Kim, Bin Tian, Harold N. Trick, Michael J. Naldrett, Robert Proctor

Nebraska Center for Biotechnology: Faculty and Staff Publications

Fusarium head blight (FHB) caused by Fusarium graminearum is one of the most devastating diseases of wheat and barley worldwide. Effectors suppress host immunity and promote disease development. The genome of F. graminearum contains hundreds of effectors with unknown function. Therefore, investigations of the functions of these effectors will facilitate developing novel strategies to enhance wheat resistance to FHB. We characterized a F. graminearum effector, FgNls1, containing a signal peptide and multiple eukaryotic nuclear localization signals. A fusion protein of green fluorescent protein and FgNls1 accumulated in plant cell nucleiwhen transiently expressed in Nicotiana benthamiana. FgNls1 suppressed …

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 …

The Wound Healing And Antibacterial Properties Of Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles, Emily N. Wandling

Theses and Dissertations

Treatments for acute respiratory distress syndrome (ARDS) are still unavailable and the prevalence of the disease has only increased due to the Covid-19 pandemic. Mechanical ventilation regiments are still utilized to support declining lung function, but they also contribute to lung damage and increase the risk of bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSC secretome and the extracellular matrix (ECM) into a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta-potential, and mass spectrometry …

Investigating Tgf-Β1 And Fibronectin Signaling In Low Oxygen Environments, Caitlin E. Williams

Theses and Dissertations

Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.

As dense tumors form, …

Finite Element Analysis Of 3d-Printed Pcl Scaffolds, Ireolu K. Orenuga, Joao Soares, Phillip D. Glass, Daeha Joung Ph.D.

UROP Posters

Finite Element Analysis of 3D-printed PCL Scaffolds for Synergizing Cellular Micro-Environment and Mechanical Stimuli to Enhance Engineered Tissue Growth in Vitro

Ireolu Orenuga,1 Phillip Glass,2 Daeha Joung,2 Joao S. Soares1

1. Department of Mechanical and Nuclear Engineering, College of Engineering, Virginia Commonwealth University
2. Department of Physics, College of Humanities & Sciences, Virginia Commonwealth University

Introduction: Tissue engineering aims to create viable and functional engineered tissues via biodegradable scaffolds and autologous cells. Scaffolds play an essential part in organizing the architecture of developing tissues and aid in the proper function of implants acutely by serving as mechanical support and long-term by …

Multipolymer Microsphere Delivery Of Sars-Cov-2 Antigens, Farah Shahjin, Milankumar Patel, Jatin Machhi, Jacob D. Cohen, Mohammad Ullah Nayan, Pravin Yeapuri, Chen Zhang, Emiko Waight, Mahmudul Hasan, Mai Mohamed Abdelmoaty, Prasanta K. Dash, You Zhou, Irene Andreu, Howard E. Gendelman, Bhavesh D. Kevadiya

Nebraska Center for Biotechnology: Faculty and Staff Publications

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective re- sponses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric micro- sphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere sys- tem can preclude the need for repeat administrations, highlighting its potential as an effective vaccine.