A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Deployment of Large Vision and Language Models for Real-Time Robotic Triage in a Mass Casualty Incident(2024) Mangel, Alexandra Paige; Paley, Derek; Aerospace Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In the event of a mass casualty incident, such as a natural disaster or war zone, having a system of triage in place that is efficient and accurate is critical for life-saving intervention, but medical personnel and resources are often strained and struggle to provide immediate care to those in need. This thesis proposes a system of autonomous air and ground vehicles equipped with stand-off sensing equipment designed to detect and localize casualties and assess them for critical injury patterns. The goal is to assist emergency medical technicians in identifying those in need of primary care by using generative AI models to analyze casualty images and communicate with the victims. Large language models are explored for the purpose of developing a chatbot that can ask a casualty where they are experiencing pain and make an informed assessment about injury classifications, and a vision language model is prompt engineered to assess a casualty image to produce a report on designated injury classifiers.Item PREPARATION OF A NANOSUSPENSION OF THE PHOTOSENSITIZER VERTEPORFIN FOR PHOTODYNAMIC AND LIGHT-INDEPENDENT THERAPY IN GLIOBLASTOMA(2024) Quinlan, John Andrew; Huang, Huang-Chiao; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Photodynamic therapy (PDT) using verteporfin (VP) has treated ocular disease for over 20 years, but recent interest in VP’s light-independent properties has reignited interest in the drug, particularly in glioblastoma (GBM) (NCT04590664). Separate efforts to apply PDT to GBM using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) have also garnered attention (NCT03048240), but, unfortunately, clinical trials using 5-ALA-induced PpIX-PDT have yet to yield a survival benefit. Previous studies have shown VP to be a superior PDT agent than 5-ALA-induced PpIX. Our lab has shown that 690 nm light activates VP up to 2 cm into the brain, while 635 nm light only activates PpIX at depths <1 cm into the brain. Additionally, VP is a more effective photosensitizer than PpIX because it has a higher singlet oxygen yield and is active in the vasculature as well as target tumor cells. However, the hydrophobicity of VP limits effective delivery of the drug to the brain for treatment of GBM.In this context, this thesis aims to re-evaluate the delivery method for VP. VP traditionally requires lipids for delivery as Visudyne. Recent shortages of Visudyne and potential drawbacks of liposomal carriers motivated our development of a carrier-free nanosuspension of VP, termed NanoVP. Previous work has shown that cellular uptake of VP is greater when delivered as NanoVP rather than liposomal VP, resulting in improved cell killing after light activation. This thesis builds on this previous work by (1) evaluating synthesis and storage parameters for NanoVP, (2) determining the pharmacokinetics, biodistribution, and brain bioavailability of NanoVP, and (3) evaluating the potential efficacy of NanoVP as a PDT and a chemotherapy agent, and by supporting development of a zebrafish model of the blood-brain barrier (BBB) for mechanistic studies of improved drug delivery to the brain.Item Formulation and Delivery of Enhanced Extracellular Vesicles for Wound Repair(2021) Born, Louis Joseph; Jay, Steven M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Despite the development of a variety of therapies, complex wounds resulting from disease, surgical intervention, or trauma remain a major source of morbidity. Extracellular vesicles (EVs) have recently emerged as an alternative approach to address this issue. In particular, EVs derived from mesenchymal stem/stromal cells (MSCs) have been shown to improve wound healing, especially via enhanced wound angiogenesis. However, despite their clearly established potential, EVs have limitations that limit clinical relevancy, including low potency and rapid clearance from the body. Additionally, the ability to sustainably deliver EVs may enhance their efficacy in wound healing. Here, we leveraged the capability of EVs to be engineered via producer cell modification to investigate the therapeutic potential of EVs from MSCs transfected to overexpress a well-established pro-angiogenic long non-coding RNA HOX transcript antisense RNA (HOTAIR). We established that HOTAIR was able to be successfully loaded into MSC EVs (HOTAIR-MSC EVs) and delivered to endothelial cells in vitro with increased functional angiogenic activity. HOTAIR-MSC EVs injected intradermally around excisional wounds also showed increased angiogenic activity in vivo in two different species of rodents and improved wound healing in diabetic mice. We further report biomaterial-enabled sustained release of EVs using injectable hydrogel nanoparticles containing a composite of thiolated hyaluronic acid, maleimide functionalized poly(ε-caprolactone), and polyethylene glycol tetraacryalte as well as 3D-printed hydrogel discs composed of gelatin methacrylate for topical application. EVs released from the formulation of both of these biomaterials retained angiogenic bioactivity. Nanoparticles containing HOTAIR-MSC EVs were injected intradermally around an excisional wound in diabetic mice and were able to increase angiogenesis and improve wound healing. EVs released from 3D-printed EV-loaded GelMa hydrogels retained bioactivity in an in vitro endothelial scratch assay. Overall, these data suggest increasing the content of lncRNA HOTAIR in MSC EVs as a promising wound healing therapeutic. Additionally, establishing a biomaterial-enabled sustained release therapeutic represents a promising translational product for clinical implementation.Item THE USE OF ACTIGRAPHY FOR RISK STRATIFICATION IN PEDIATRIC OBSTRUCTIVE SLEEP APNEA(2018) Bertoni, Dylan Gregory; Isaiah, Amal; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Objectives. (i) To determine the feasibility of using actigraphy to identify sleep interruption in children with suspected obstructive sleep apnea (OSA); (ii) to assess the utility of actigraphy for prediction of OSA severity. Subjects and Methods. Ten healthy children aged 2 to 15 years with suspicion for OSA underwent polysomnography (PSG) with actigraphy. Statistical learning algorithms were used to (i) identify sleep-related respiratory events (awake, asleep, hypopneas and apneas), and (ii) predict OSA severity (mild, moderate and severe) utilizing actigraphy counts. Results. No adverse events were identified. Actigraphy counts were obtained in all 10 children. Linear discriminant analysis identified 100% of patients with severe OSA. Actigraphy counts reliably identified hypopneas and awakenings but not apneas. Conclusions. Actigraphy counts may provide effective risk stratification for pediatric OSA. Further investigations are necessary to investigate the utility of using actigraphy and pulse oximetry together to identify all respiratory events during sleep.Item TARGETING MAGNETIC NANOCARRIERS IN THE HEAD FOR DRUG DELIVERY AND BIOSENSING APPLICATIONS(2016) Ramaswamy, Bharath; Shapiro, Benjamin; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Magnetic nanocarriers have proven to be effective vehicles for transporting therapeutic and diagnostic agents in the body. Their main advantage is their ability to be manipulated by external magnets to direct them to specific targets in the body. In this dissertation, I study the transport, safety and efficacy of moving drug coated magnetic nanocarriers in different types of tissue. Movement of magnetic nanocarriers of sizes ranging from 100 nm to 1µm with different biocompatible coatings (Starch, PEG, Lipid and Chitosan) was quantified in different tissue types using an automated cryostat system. The safety of moving magnetic nanocarriers in live rodent brain tissue was assessed using electrophysiology, calcium imaging and immunohistochemistry. Moving magnetic nanocarriers in brain tissue did not significantly affect the firing ability of single neurons, synaptic connectivity and the overall functioning of the neuron network. As part of efficacy studies, steroid-eluting magnetic nanoparticles were targeted using external magnets to the inner ear of mice to counter hearing loss caused by cisplatin chemotherapeutics. This targeted steroid delivery to the cochlea significantly reduced the change in hearing threshold at 32 KHz caused by cisplatin injections and protected the hair cells from significant damage. Finally, I explore the potential of spin-transfer torque nano-oscillators, which are multi-layered ferromagnetic nanocarriers, as high-resolution in vivo wireless biosensors. These nanocarriers have been shown to detect action potentials from crayfish lateral giant neurons and that the microwave magnetic signals from these devices can be detected wirelessly by near field induction.Item Engineering Biodegradable Vascular Scaffolds for Congenital Heart Disease(2015) Melchiorri, Anthony John; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The most common birth defects worldwide are congenital heart defects. To treat these malformations in a child’s cardiovascular system, synthetic grafts have been used as a primary intervention. However, current grafts suffer from deficiencies such as minimal biological compatibility, inability to grow and adapt, and high failure rates. Additionally, the grafts are not customized to the patient, which may lead to graft failure given that defects may vary significantly from patient to patient. The work presented here aims to adapt tissue engineering paradigms to develop customizable vascular grafts for congenital heart defects using to reduce the long-term risk and the number of surgeries experienced by patients. The first component of this research focuses on solvent-cast vascular grafts. This system of fabrication was used to explore how various strategies and graft modifications affect the graft’s performance in vivo. Grafts were fabricated with the mechanical properties necessary to withstand the stresses of a physiological environment and support neotissue formation. To improve tissue formation, the grafts were modified with bioactive molecules to improve vascular tissue growth. In addition, the grafts were combined with a tissue perfusion bioreactor. The bioreactor applied fluid flow to support cell seeding, differentiation, and growth of endothelial progenitor cells on the grafts, demonstrating a robust strategy for tissue formation prior to implantation. The second component of this research centers on the development of a biomaterial for 3D printing. 3D printing offers unparalleled customizability, as a graft can be designed based on medical images of a patient, tested via computer modeling, and then printed for implantation. A resin was developed consisting to produce grafts that were mechanically compatible with native blood vessels and maintained patency and tissue formation six months after implantation. The library of 3D printed vascular graft materials was also expanded by creating a novel copolymer resins, which varied in mechanical properties and degradation profiles. In addition, the concepts and strategies of biofunctionalization developed in the solvent-cast vascular grafts can be combined with the 3D printed graft strategies. Grafts designed, printed, and modified using these combinatorial approaches can greatly improve the long-term outcomes of treating congenital heart disease.Item Development of Carbon Nanotube Field-Effect Transistor Arrays for Detection of HER2 Overexpression in Breast Cancer(2011) Aschenbach, Konrad Hsu; Gomez, Romel D; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We developed a carbon nanotube biosensor platform that was deployed at the National Cancer Institute and successfully detected the HER2 oncogene in real cancer cells at clinically relevant levels. HER2 is a receptor protein that resides on the surface of certain cancer cells and is associated with higher aggressiveness in breast cancers. Overabundance of HER2 at the chromosomal, cell surface, and intermediate gene expression levels can all indicate a dangerous HER2 status. At the present, testing for HER2 status requires labor-intensive laboratory procedures using expensive reagents. Cost remains the major barrier to widespread screening. We propose an integrated electronic testing platform based on direct label-free gene detection. The system would integrate the various labor-intensive processes that are usually performed by skilled laboratory technicians. The heart of the system is an array of carbon nanotube field-effect transistors that can detect unlabelled nucleic acids via their intrinsic electric charges. We developed a scalable fabrication technique for carbon nanotube biosensor arrays, hardware and software for data acquisition and analysis, theoretical models for detection mechanism, and protocols for immobilization of peptide nucleic acid probes and hybridization of nucleic acids extracted from cells. We demonstrated detection of HER2 from real cell lines which express cancer genes, thereby lowering the technological barrier towards commercialization of a low-cost gene expression biosensor. The system is suitable for lab-on-a-chip integration, which could bring rapid, low-cost cancer diagnoses into the clinical setting.