Engineering Commons^™

Levofloxacin Incorporated Extracellular Matrix Nanoparticles For Pulmonary Cystic Fibrosis Infections, Raahi Patel

Theses and Dissertations

Cystic fibrosis (CF) is a progressive genetic disorder that affects around 40,000 people in the United States. CF is characterized by a mutation in the CFTR protein that causes dysregulated ion transport across epithelial cells, producing viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in CF patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX) that functions to inhibit bacterial replication, but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

Toxicological Inhalation Effects Of Metal-Based Nanoparticle Aerosols As Studied By A Portable In Vitro Exposure Cassette, Lynn E. Secondo

Theses and Dissertations

The toxicology of aerosols in occupational settings is often performed through particle collection on a filter followed by reconstitution into cell culture media which can alter the biological effects. Current in vitro exposure systems require additional instruments to control temperature and humidity, making the system bulky and difficult to take to the field. The Portable In Vitro Exposure Cassette (PIVEC) was designed for personal monitoring, characterized using copper nanoparticles, tested with alveolar cells, and set-up for real-time monitoring. Three differently sized copper nanoparticles, 40-800 nm, were dispersed as a dry aerosol and measured gravimetrically and on a number concentration basis …

Modeling The Spatiotemporal Dynamics Of Cells In The Lung, Joshua Jeremy Pothen

Graduate College Dissertations and Theses

Multiple research problems related to the lung involve a need to take into account the spatiotemporal dynamics of the underlying component cells. Two such problems involve better understanding the nature of the allergic inflammatory response to explore what might cause chronic inflammatory diseases such as asthma, and determining the rules underlying stem cells used to engraft decellularized lung scaffolds in the hopes of growing new lungs for transplantation. For both problems, we model the systems computationally using agent-based modeling, a tool that enables us to capture these spatiotemporal dynamics by modeling any biological system as a collection of agents (cells) …

Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young

Theses and Dissertations

Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …

The Molecular And Mechanical Mechanisms Of The Age-Associated Increase In The Severity Of Experimental Ventilator Induced Lung Injury, Joseph Ames Herbert

Theses and Dissertations

Abstract

Background

The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and mortality. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood.

Pulmonary edema is a hallmark of VILI and the severity of edema increases with age. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress (ARDS) patients, but has not been investigated in VILI. We hypothesized that age-associated increases in pulmonary edema promote age-related increases in ventilator-associated mortality. Endoplasmic reticulum (ER) …

Lung Alveolar And Tissue Analysis Under Mechanical Ventilation, Trenicka Rolle

Theses and Dissertations

Mechanical ventilation has been a major therapy used by physicians in support of surgery as well as for treating patients with reduced lung function. Despite its many positive outcomes and ability to maintain life, in many cases, it has also led to increased injury of the lungs, further exacerbating the diseased state. Numerous studies have investigated the effects of long term ventilation with respect to lungs, however, the connection between the global deformation of the whole organ and the strains reaching the alveolar walls remains unclear. The walls of lung alveoli also called the alveolar septum are characterized as a …

Oligospermines For Non-Viral Sirna Delivery, Maha Elsayed

Wayne State University Theses

In this thesis, delivery systems for siRNA delivery are introduced with special attention to non-viral vectors. Many successful vectors used in vivo were reviewed. Our work focused on the effect of different architectures of oligospermine polmers on their suitability for siRNA delivery in lung cancer cells. Different archituctures showed different polyplex structures and variable transfection efficiencies. Moreover, we presented a review on nanoimprint lithography techniques with an outlook on possible biological applications in the field of gene and drug delivery.

Optimization Of Spray Droplet Size For Drug Delivery To The Deep Lung, Renee Worden

Electronic Theses and Dissertations

The lower respiratory regions of the lung boast over 900 million alveoli with a combined 85 m2 of surface area of near direct access to the bloodstream. Within the last century the immense potential of the deep lung as a site for the delivery of drugs has begun to be exploited and today pulmonary delivery of aerosolized therapeutic is commonplace. However, the high inter- and intra-patient variability in dosing is almost completely ignored. Currently, no steps are being taken to mitigate the sources of variability beyond injection into the upper airways. This study seeks to prove that a careful selection …

Towards A Fluid Solid Interaction Model Of A Dynamic Lung, Justin C. Jacobs

Electronic Theses and Dissertations

Because the pulmonary system is a site for both environmental particulate contamination, as well as drug delivery into the body, numerous research groups have focused on precisely understanding its inner-workings. Past research has demonstrated the need to realistically model the lung walls in order to accurately capture the complex airflow profile throughout all of the branches. Since this is paramount to properly replicating particulate transport in the lung, computational fluid dynamics simulations on their own are inadequate, as they cannot account for lung wall dilation. Only by coupling the fluid and solid domains can natural lung behavior can be effectively …

Quantitative Evaluation Of Redox Processes In Intact Rat Lungs And Endothelial Cells And The Effect Of Hyperoxia, Zhuohui Gan

Dissertations (1934 -)

A common initial treatment of hypoxemia in patients with lung failure secondary to acute lung injury (e.g., adult respiratory distress syndrome) is oxygen (O₂) therapy (hyperoxia). However, prolonged O₂ therapy causes lung O₂ toxicity, which can further impair lung functions. The rat model of lung O₂ toxicity replicates key features of human lung O₂ toxicity. In addition, rats develop tolerance or susceptibility to 100% O₂ by pre-exposing them to 85% O₂ (hyper-85) or 60% O₂ (hyper-60) for 7 days, respectively. Therefore, the long-term objectives of this study are to elucidate mechanisms …

Pulmonary Particle Deposition In Relation To Age, Body Weight, And Species, Lisa M. Weber

Electronic Theses and Dissertations

As a result of dissimilarity in lung morphometry and physiological conditions, therapeutic aerosol particles deposit differently in humans of various ages and body weights. These particles also deposit differently in non-human species that are often utilized in inhalation and dosing studies. The focus of this work is to determine the optimal particle size and deposition (traditional efficiency and volume-weighted) of therapeutic particles in humans of both genders ranging in age from 3 months old to 21 years old and three non-human species (B6C3F₁ mouse, Long-Evans hooded rat, and Beagle dog). This study finds that in humans, both optimal …

Development Of A Software Application To Extract The Features Of Normal Respiratory Sounds From The Lungs And The Trachea, Ranjani Sabarinathan

Theses and Dissertations

Auscultation has been widely regarded as one of the most important noninvasive diagnostic tools for clinical diagnosis of the respiratory tract. The purpose of this thesis was to develop a software application capable of extracting the key features of respiratory sound signals from the lungs and trachea of healthy persons. The efficacy of the program was evaluated by the verification of the important features of the sound signals from the left and right lungs and the trachea such as 1) right and left lung symmetry and 2) dissimilarity between the trachea and both lungs. The program was developed in LabView …