Molecular, Cellular, and Tissue Engineering Commons^™

A Single Cell Pair Mechanical Interrogation Platform To Study Cell–Cell Adhesion Mechanics, Amir Monemianesfahani

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

A Systematic Review And Meta-Analysis On The Efficacy Of Stem Cell Therapy On Bone Brittleness In Mouse Models Of Osteogenesis Imperfecta, Lauren Battle, Shoshana Yakar, Alessandra Carriero

Publications and Research

There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection …

Correlating Diffusional Dynamics And Receptor Tyrosine Kinase Function Using Single Quantum Dot Tracking, Irais Ortiz Caraveo

Biomedical Engineering ETDs

Epidermal growth factor receptor (EGFR) signal transduction is initiated via ligand (EGF) binding, followed by dimerization, autophosphorylation of the C-terminal tails, and recruitment of proteins that form a larger signaling complex to propagate the signal. We explored the relationship between receptor mobility and signaling using single-particle tracking (SPT) by examining the diffusional dynamics of EGFR and two truncation mutants to understand whether mobility changes are correlated with signaling. Results revealed that phosphorylation of the C-terminal tail of EGFR is required for maximal reduction in mobility that occurs with EGF stimulation, indicating that receptor mobility is a read-out for receptor signaling. …

Synthesis And Performance Testing Of Ecm Fiber Scaffolds, Cassandra Reed

Graduate Theses and Dissertations

The progression of regenerative medicine has advanced the treatment of multiple illnesses and injuries throughout the years. A good example of the benefits of this research is the work that has gone into volumetric muscle loss (VML), where more than 20% of the muscle is loss. Skeletal muscle makes up 40% of the human body so a loss of that size greatly diminishes the strength, the flexibility, physiology, and quality of life of the injured individual. For that reason, various techniques are used to counteract the loss of structure and innate cellular signaling in order to circumvent that from happening. …

Arhgdia Confers Selective Advantage To Dissociated Human Pluripotent Stem Cells, Marion J. Riggs, Steven D. Sheridan, Raj R. Rao

Biomedical Engineering Faculty Publications and Presentations

Human pluripotent stem cells (hPSCs) have generated significant interest in the scientific community based on their potential applications in regenerative medicine. However, numerous research groups have reported a propensity for genomic alterations during hPSC culture that poses concerns for basic research and clinical applications. Work from our laboratory and others has demonstrated that amplification of chromosomal regions is correlated with increased gene expression. To date, the phenotypic association of common genomic alterations remains unclear and is a cause for concern during clinical use. In this study, we focus on trisomy 17 and a list of candidate genes with increased gene …

Review And Analysis Of Methods For Measuring Concentration Of Suspended Substances And Active Sludge During Biological Treatment Of Waste Water, Maxsud Maxmudov, Siroj Nurov, Zafar Qo'ziev, Sanjar Sidiqov

Scientific-technical journal

This work analyzes and compares the measuring and technical characteristics of methods for measuring and controlling the parameters of activated sludge in the processes of biological wastewater treatment. As methods for measuring the concentration of activated sludge, methods such as the optical method, the ultrasonic method and the method for measuring the nuclear density of a liquid are considered. The principles of operation of each of these methods are illustrated with graphic drawings for more clarity of the interaction of the measuring signal with the particles of the measured medium. At the end of the work, conclusions on the characteristics …

The Impact Of Myoblast Transplantation On Collateral Capillary Arteriogenesis And Macrophage Phenotype, Christine Hue Do

Biomedical Engineering

Gangrene, pain, loss of limb function, amputation, and death are only few of the grievous consequences associated with peripheral arterial disease (PAD), a vascular disease caused by an obstruction that narrows the blood vessels. Since some patients have collateral vessels that can re-route blood to its downstream destination, much focus has been spotlighted upon discovering the mechanism of this process, termed arteriogenesis, as well as cell therapies to increase arterial diameter of collateral vessels. Since some patients do not have native pre-existing collateral vessels, another method to re-route blood is through arterialized collateral capillaries (ACC), which is the conversion of …

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 …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

University Scholar Projects

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

Honors Scholar Theses

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

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 …

Guide Rnas Preparation For In-Vitro Crispr-Cas9 Complex Delivery Targeting Genes That Affect Wound Healing., Prashant Khatiwada

Biomedical Engineering Undergraduate Honors Theses

CRISPR-Cas9 technology has widely been used as a viable genome engineering platform to make site-specific insertion, deletion, and breaks. The nuclease dead version of Cas9 or dCas9 can be used for the activation and repression of target gene sites using specific activation or repression domains. In this study, CRISPR guide RNAs were designed for a CRISPR inhibition approach to repress the transcriptional activity of the target genes. An expression plasmid vector composed of a U6 promoter sequence, BbsI restriction sites, and a chimeric gRNA sequence was digested, and the phosphorylated forward and reverse gRNAs were ligated with the plasmid vector. …

Evaluating Cellular Response Of Different Valve Interstitial Cell (Vic) Phenotypes To Angiotensin I, Smit Patel

Biomedical Engineering Undergraduate Honors Theses

Calcific Aortic Valve Disease (CAVD), one of the leading causes of death in the United States, is characterized by diminished functioning and limited movement of the aortic valve (AV) due to increased thickening, disorganized extracellular matrix elastin fibers, increased collagen content, and abnormal deposition and formation of calcium nodules on the AV [1, 2]. There are two types of CAVD: i) Aortic valve sclerosis (AVS), in which patients suffer from tissue hardening, fibrosis, and early calcification, and ii) calcific aortic stenosis (CAS), representative by excessive calcification on the AV and reduced AV opening, are the two main forms of CAVD …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

Quantifying The Effect Of Intrinsic Aging On Skin Microstructure And Mechanical Function Using Multiphoton Microscopy, Alan Edward Woessner

Graduate Theses and Dissertations

Over the next couple of decades, the number of elderly individuals is expected to double, bringing increased healthcare spending due to seemingly minor injuries to skin. In skin, the 3D dermal collagen fiber network, which is the primary load-bearing structure, undergoes changes in organization and composition due to intrinsic aging. However, the relationships between altered microstructure and mechanical function is not well understood. Quantitative imaging techniques have been used in the past to link skin structure to mechanical function, but previous analysis has been limited to 2D assessments. Multiphoton microscopy (MPM) is a non-destructive imaging technique with intrinsic depth-sectioning capabilities, …

Peptoid-Based Microsphere Coatings For Biomaterial Applications, Jesse Leland Roberts

Graduate Theses and Dissertations

Peptoids are peptidomimetic oligomers that predominantly harness similarities to peptides for biomimetic functionality. The incorporation of chiral, aromatic side chains in the peptoid sequence allows for the formation of distinct secondary structures and self-assembly into supramolecular assemblies, including microspheres. Peptoid microspheres can be coated onto substrates for potential use in biosensor technologies, tissue engineering platforms, and drug-delivery systems. They have the potential for use in biomedical applications due to their resistance to proteolytic degradation and low immunogenicity. This dissertation focuses on the physical characteristics and robustness of the peptoid microsphere coatings in various physiological conditions, along with their ability to …

Evaluating The Effects Of Wood Source On The Physicochemical Properties Of Crosslinked Cellulose Nanocrystals, Helena Tchoungang Nkeumen

Graduate Theses and Dissertations

Cellulose is an abundant and naturally occurring biopolymer that has been used by humans for food, shelter, and clothing for about two centuries now. Highly crystalline nanoparticles derived from cellulose, called cellulose nanocrystals (CNCs), show great potential to meet the rising need for sustainable and nontoxic materials for biomedical applications. However, multiple biomedical applications of CNCs, such as those involving their use in tissue engineering scaffolds, require CNC-based structures to be stable in aqueous environments, a property that native CNCs do not possess due to their inherent hydrophilicity. Chemical crosslinking of CNCs addresses this issue by providing aqueous stability to …

Oxone® Mediated Tempo-Oxidized Cellulose Nanomaterials: Material Characterization, Ultrafiltration Membrane Separations, And Thin Film Composite Gas Transport Analysis, John Phillips Moore

Graduate Theses and Dissertations

Cellulose nanomaterials (CNMs) are derived from plant matter and are comprised of nanoscopic cellulose crystals and fibers. They have a diverse set of applications, from cosmetics to oil recovery. This study focuses on the properties of Oxone® mediated TEMPO-oxidized cellulose nanomaterials (OTO-CNMs) and their use in controlling the transport properties of polymeric substrates. Synthesis and characterization of cellulosic nanoparticles have resulted in the creation of OTO-CNMs with properties that increase hydrophilicity. With added hydrophilicity, OTO-CNMs possess lower fouling propensity, making them ideal membrane additive for transport limited separations such as hemodialysis.

To utilize the material and unique properties thereof, this …

Development And Applications Of In-Vitro And In-Silico Models Of The Cardiovascular System To Study The Effects Of Mechanical Circulatory Support., Moustafa Meki

Electronic Theses and Dissertations

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. With ongoing interest in CVDs treatment, preclinical models for drug/therapeutic development that allow for fast iterative research are needed. Owing to the inherent complexity of the cardiovascular system, current in-vitro models of the cardiovascular system fail to replicate many of the physiological aspects of the cardiovascular system. In this dissertation, the main concern is with heart failure (HF). In advanced HF, patients may receive Left Ventricular Assist Devices (LVADs) as a bridge to transplant or destination therapy. However, LVADs have many limitations, including inability to adapt to varying tissue demand …

Mapping The Domain Of Rna Helicase Ddx1 That Interacts With The Ns1 Of Influenza A Viruses, Elise Wyatt

Biomedical Engineering Undergraduate Honors Theses

Of the known influenza virus strains, influenza A viruses (IAVs) are the most catastrophic due to their highly contagious nature and possibly life-threatening symptoms. IAVs invade a host cell and enter the nucleus where they use the cell’s nuclear machinery for replication of their viral RNA genome which is then exported to neighboring cells to establish a productive infection. Host pathogen recognition receptors (PRRs) respond to viral infection by signaling the cell to produce type I interferons (IFNs) to fight the foreign invader. Non-structural protein 1 (NS1) of IAVs, a major component in the regulation of viral replication, opposes host …