Engineering Commons^™

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Restoration Of Bone Material And Microstructural Properties After Long-Term Remodeling Suppression, Abigail A. Coffman

Dissertations and Theses

Anti-resorptive drugs, principally bisphosphonates (BPs), are the mainstay of osteoporosis treatment. They work by inhibiting bone resorption/remodeling, thus preventing bone loss. However, long-term suppression of bone resorption adversely affects bone tissue mechanical properties, even while conserving bone mass. Lack of remodeling leads to accumulation of fatigue-induced microdamage, altered matrix mineralization and reduction in normal bone tissue heterogeneity, causing impaired strength and fracture toughness. The most severe consequence to patients, while rare, is Atypical Femur Fractures (i.e., complete fatigue fractures of the femoral shaft). To counteract the effects of long-term remodeling suppression, a temporary break in BP treatment (a "drug holiday) …

Osteocyte Activity And Skeletal Muscle Relative Gene Expression Profiling After Short-Term Muscle Paralysis, Michelle Gelbs

Dissertations and Theses

Mechanical loading is essential for maintaining bone tissue. Reduced mechanical loading has been shown to have a negative effect on bone, and can result in the development of disuse osteoporosis. Disuse models of muscle inactivity and immobilization, like the Botox model used in this study, result in changes in the bone microarchitecture, the mechanisms behind which are not fully understood. In a previous four-week Botox disuse study, skeletally mature 20- week-old rats experienced degradation of intracortical bone, increased vascular porosity, and decreased osteocyte lacunar density in the tibiae. The focus of this study was to explicate a potential source of …

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 …

Development Of An Injectable Methylcellulose Hydrogel System For Nucleus Pulposus Repair And Regeneration, Nada A. Haq-Siddiqi

Dissertations and Theses

Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic …

Characterization Of Bone Pathology In Sickle Cell Disease And Therapeutic Strategies, Mykel D. Green

Dissertations and Theses

Sickle cell disease (SCD) is a genetic hemoglobinopathy that has grown into a global health concern. While the advances in medical treatment and management of SCD during childhood have drastically improved the overall survival of children, the transition from pediatric to adult services is significantly inadequate in comparison. Life expectancies of patients with SCD in first world countries such as the United States are shortened to averages of 42 and 48 years for men and women, respectively. Despite the increasing number of people living with SCD, remarkably, few detailed studies have described the clinical course and complications of the disease …

Translational Modeling Of Non-Invasive Electrical Stimulation, Dennis Quangvinh Truong

Dissertations and Theses

Seminal work in the early 2000’s demonstrated the effect of low amplitude non-invasive electrical stimulation in people using neurophysiological measures (motor evoked potentials, MEPs). Clinical applications of transcranial Direct Current Stimulation (tDCS) have since proliferated, though the mechanisms are not fully understood. Efforts to refine the technique to improve results are on-going as are mechanistic studies both in vivo and in vitro. Volume conduction models are being applied to these areas of research, especially in the design and analysis of clinical montages. However, additional research on the parameterization of models remains.

In this dissertation, Finite Element Method (FEM) models of …

Knockdown Of Heparan Sulfate Via Ndst1 Knockout Does Not Inhibit Mouse Aortic Endothelial Cell Alignment In-Vivo, John Diaz De Leon Iii

Dissertations and Theses

Atherosclerotic plaque localizes in predictable areas such as arches and bifurcations which are characterized by disturbed flow patterns and the resulting damage and dysfunction to the endothelium. Endothelial cells (ECs) under sustained laminar flow align in the direction of flow; however, under disturbed flow conditions, ECs sustain damage to their glycocalyx (GCX) which results in unaligned and rounder cells. An investigation into the role of NDST1 sulfation of heparan sulfate (HS), a key component of many proteoglycans which make up the GCX, was conducted. The descending aortas (DAs) of transgenic mice with conditional knockouts (KOs) of NDST1 in vascular ECs …

Automatic Optimum Atlas Selection For Multi-Atlas Image Segmentation Using Joint Label Fusion, Kofi Agyeman

Dissertations and Theses

Multi-atlas image segmentation using label fusion is one of the most accurate state of the art image segmentation techniques available for biomedical imaging applications. Motivated to achieve higher image segmentation accuracy, reduce computational costs and a continuously increasing atlas data size, a robust framework for optimum selection of atlases for label fusion is vital. Although believed not to be critical for weighted label fusion techniques by some works (Sabuncu, M. R. et al., 2010, [1]), others have shown that appropriate atlas selection has several merits and can improve multi-atlas image segmentation accuracy (Aljabar et al., 2009, [2], Van de Velde …