Biomaterials Commons^™

De Novo Protein Binding To Zinc Oxide Through Biomineralization Pathways, Jean-Mark A. Francis

Theses and Dissertations

De novo proteins are structurally distinct from proteins found in nature and thus capable of having their amino acid sequence modified to accomplish tasks such as increasing protein-nanoparticle binding without unfolding or decomposing. Zinc Oxide nanoparticles are functionally distinct from their bulk counterparts and are widely used as semiconductors in a variety of fields such as medicine and agriculture. With demand for these nanoparticles increasing, environmentally sustainable methods of Zinc Oxide nanoparticle synthesis are being investigated as an eco-friendly alternative to currently utilized but environmentally hazardous chemical and physical techniques. This research investigates the binding characteristics between Zinc Oxide nanoparticles …

Development Of Rolipram Loaded Pgp Nanoparticles For Spinal Cord Injury Repair, Zhen Liao

All Dissertations

Spinal cord injury (SCI) leads to devastating neurological deficits due to primary mechanical damage and secondary injury mechanisms, including inflammation, oxidative stress, excitotoxicity, and inhibitory scarring, which collectively impede neural regeneration. One key aspect of SCI pathology is a significant reduction in cyclic adenosine monophosphate (cAMP) levels, primarily due to increased phosphodiesterase (PDE 4) activity. As a ubiquitous second messenger, cAMP regulates key signaling pathways, including protein kinase A (PKA) / cAMP response element-binding protein (CREB) and exchange protein activated by cAMP 2 (EPAC2). Therefore, restoring/increasing cAMP level is one of the major therapeutic strategies to reduce neurotrauma and restore …

Explorations Of Dna-Single-Walled Carbon Nanotube Interactions To Develop Multiplexed Molecularly Specific Biosensors For Inflammation, Amelia K. Ryan

Dissertations and Theses

Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-12 (IL-12) are central regulators of immune signaling and key biomarkers of disease, yet existing assays for their detection remain slow, invasive, and lack multiplexing ability. This dissertation advances the development of single-walled carbon nanotube (SWCNT) optical nanosensors capable of real-time, multiplexed, and molecularly specific cytokine detection through innovative use of single-stranded DNA (ssDNA) interfaces.

First, an IL-6-specific DNA aptamer was employed as both a dispersing agent and recognition probe for SWCNT fluorescence sensing. Sequence modifications, including anchor domains, truncations, and thermally induced refolding, were systematically tested to optimize sensitivity and selectivity. The …

The Bacteriostatic, Regenerative, And Immunomodulatory Properties Of Extracellular Matrix Particles For Lung Injury, Keera P. Rhoads

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a prevalent, life-threatening lung condition, affecting nearly 200,000 Americans annually, with a 40% international mortality rate. There is no cure for ARDS, and current pharmacological treatments have limited effectiveness. Symptoms can be mitigated with mechanical ventilation, though this often leads to ventilator-induced lung injuries (VILI) and puts critically ill patients at risk of infections, including ventilator-associated pneumonia (VAP). A promising therapeutic is the extracellular matrix (ECM), a complex network of structural proteins and bioactive molecules that has been shown to have anti-inflammatory properties and prevent fibrosis. We aim to utilize the regenerative and immunomodulatory …

Multifunctional Peptides To Improve Nucleic Acid Delivery For Ovarian Cancer Treatment, Kharimat Lora Alatise

All Dissertations

RNA interference (RNAi) therapies, such as small interfering RNA (siRNA), offer a high-precision approach to reducing the expression of disease-promoting genes with minimal off-target effects. For aggressive diseases like ovarian cancer, RNAi therapy can serve as a robust treatment modality if delivered successfully. Over 70% of ovarian cancer patients are diagnosed in stages three and four, where the disease becomes more difficult to treat. High relapse rates and drug resistance in these stages demonstrate the need for novel strategies to sensitize tumors to chemotherapy, making siRNA a promising avenue for targeting resistance-associated oncogenes.

However, the delivery of siRNA remains a …

Targeted Drug Delivery: Investigating Protein Corona Behavior, Atharva Markale

Theses

Due to high specificity and less toxicity, nanoparticles have become promising for targeted drug delivery against cancer, although they face challenges when they enter the bloodstream, making their behavior unpredictable. The deposition of proteins on nanoparticles, the protein corona, changes their biosignature, affecting their circulation, drug release potency, targeting ability, and immunogenicity. The continuous exchange of protein layers on a nanoscale is complex to analyze.

Nanoparticle tracking analysis (NTA) is a method to characterize nanoparticles in blood plasma by combining principles of light scattering microscopy and Brownian motion. In this work, time-dependent experiments with plasma were conducted to analyze the …

Stimuli-Responsive Glycopolymeric Nanoparticles To Boost Tumor Immunogenicity Through Macrophage-Targeted Therapy, Oluwaseyi Shofolawe-Bakare

Electronic Theses and Dissertations

Tumor-associated macrophages (TAMs) play a substantial role in sculpting the tumor microenvironment (TME) into an immunosuppressive bastion that undermines immune surveillance and enables tumor progression. They therefore represent a promising therapeutic target to make the TME more conducive for anti-tumor immunity and greatly improve treatment outcomes in cancers that are highly resistant to conventional forms of therapy. Several medications have been developed to modulate the activities of TAMs, showing tremendous potential, but these medications lack specificity for TAMs making their use susceptible to adverse side effects that could outweigh prospective benefits. Sophisticated delivery vehicles that can preferentially deliver these medications …

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 …

Nano-, Encapsulated Manganese Oxide (Nemo) Particles For Mri Enhancement In Microfluidic Tumor Models, Kasey Alexis Freshwater

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer is among the deadliest cancers in women, with approximately 2.3 million new cases and 685,000 deaths reported globally in 2020 alone. Magnetic Resonance Imaging (MRI) is commonly used to diagnose, stage, and develop treatment plans for patients predisposed to breast cancer. However, current MRI-based screening of breast cancer has high false-positive rates up to 25%, leading to unnecessary invasive follow-up screening and testing. The gold-standard intravenous gadolinium (Gd)-based contrast agents (GBCAs) account for false-positive rates because they are always “ON”, providing a constant MRI signal that highlights both benign and malignant tumors. The work detailed in this thesis …

Liver Cancer: Current And Future Trends Using Biomaterials, Sue Anne Chew, Stefania Moscato, Sachin George, Bahareh Azimi, Serena Danti

Health & Biomedical Sciences Faculty Publications

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer diagnosed and the second leading cause of death worldwide. Despite advancement in current treatments for HCC, the prognosis for this cancer is still unfavorable. This comprehensive review article focuses on all the current technology that applies biomaterials to treat and study liver cancer, thus showing the versatility of biomaterials to be used as smart tools in this complex pathologic scenario. Specifically, after introducing the liver anatomy and pathology by focusing on the available treatments for HCC, this review summarizes the current biomaterial-based approaches for systemic delivery and implantable tools …

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, …

Nanomedicine Drug Delivery Across Mucous Membranes, Michael G. Lancina Iii

Theses and Dissertations

NANOMEDECINE DRUG DELIVERY ACROSS MUCOUS MEMBRANES

By Michael G. Lancina III

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth Univeristy, 2017.

Major Director: Dr. Hu Yang, Associate Professor, Chemical and Life Science Engineering

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In …

Synthesis And Characterization Of Curcumin Polymer For Application In Radiation Induced Lung Damage, Mark C. Bailey

Theses and Dissertations--Chemical and Materials Engineering

Radiotherapy is used as a primary treatment for many cancers, including lung cancer. Although radiotherapy has proven to be an effective cancer treatment, its use is heavily limited due to the peripheral toxicity to healthy tissue. In this work, the antioxidant, curcumin, was tested as a radioprotectant to reduce radiation damage to healthy cells. Curcumin has been limited in use due to its poor bioavailability. In order to avoid problems associated with free curcumin delivery, curcumin poly(beta-amino ester) (CPBAE) was synthesized.

The first study investigated the in vitro radioprotection effect of curcumin in HUVEC dosed with gamma radiation. Cells treated …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Developent Of A Phospholipid Encapsulation Process For Quantum Dots To Be Used In Biologic Applications, Logan Grimes

Master's Theses

The American Cancer Society predicts that 1,665,540 people will be diagnosed with cancer, and 585,720 people will die from cancer in 2014. One of the most common types of cancer in the United States is skin cancer. Melanoma alone is predicted to account for 10,000 of the cancer related deaths in 2014. As a highly mobile and aggressive form of cancer, melanoma is difficult to fight once it has metastasized through the body. Early detection in such varieties of cancer is critical in improving survival rates in afflicted patients. Present methods of detection rely on visual examination of suspicious regions …

Targeted Multistage Delivery Of Nanoparticles To The Bone Marrow, Aman Mann

Dissertations and Theses (Open Access)

Bone marrow is a target organ site involved in multiple diseases including myeloproliferative disorders and hematologic malignancies and metastases from breast and prostate. Most of these diseases are characterized with poor quality of life, and the treatment options are only palliative due to lack of delivery mechanisms for systemically injected drugs which results in dose limitation to protect the healthy hematopoietic cells. Therefore, there is a critical need to develop effective therapeutic strategies that allow for selective delivery of therapeutic payload to the bone marrow. Nanotechnology-based drug delivery systems provide the opportunity to deliver drugs to the target tissue while …

Structure And Optical Properties Of Self-Assembled Multicomponent Plasmonic Nanogels, Tao Cong, Satvik N. Wani, Peter Anthony Paynter, Radhakrishna Sureshkumar

Biomedical and Chemical Engineering - All Scholarship

Multicomponent plasmonic nanogels (PNGs) capable of broadband absorption of light in the 400-700 nm wavelength range were synthesized by the self-assembly of metal nanoparticles with wormlike surfactant micelles. Small angle x-ray scattering and rheological experiments suggest that the nanoparticles bridge micelle fragments to aid the formation a stable gel phase with exceptional color uniformity. Their optical absorbance could be robustly tuned by changing the nanoparticle type (Au/Ag), size, shape, and/or concentration. The PNGs have relatively low viscosity and are thermoreversible. Potential applications to the manufacturing of coatings and interfaces for solar energy harvesting and reconfigurable optical devices can be envisioned.