Biomaterials Commons^™

Engineering Plga Nanoparticle Size To Modulate Immune Responses After Spinal Cord Injury, Daniel J. Kolpek

University of Kentucky Doctoral Dissertations

Spinal cord injury is a severe and debilitating condition that often results in lifelong complications, including paralysis. Many of these chronic outcomes are driven by a sustained inflammatory response at the injury site, which limits tissue regeneration and functional recovery. As a result, therapeutic strategies that modulate this immune response have gained significant interest. Polymer based nanoparticle therapies have emerged as a promising approach due to their ability to interact with and influence immune cell behavior. Importantly, the physicochemical properties of nanoparticles can be precisely tuned to optimize these effects. Among these properties, size has been shown to influence key …

Magnetic Heating Efficiency Of Magnetite Nanoparticles: Dependence On Size And Alternating Magnetic Field, Sarah E. Kubican

Theses and Dissertations--Biomedical Engineering

Magnetic heating mediated by magnetic iron oxide nanoparticles (MION) has several clinical applications including cancer thermal therapy, tissue thawing for organ preservation, and magnetogenetics. However, current models of magnetic heating, including the widely used linear response theory, inadequately predict MION heating efficiency. An experimental study covering alternating magnetic field (AMF) strengths and frequencies ranging from 3.98 – 27.85 kA/m and 103.6 – 984.1 kHz, respectively, with a range of MION core diameters 9.5- 30.3 nm was conducted to elucidate the relationships between these AMF parameters and MION sizes and the resulting heating efficiencies. Heating efficiency was found to increase approximately …

A Pyrrole Modified 3,4-Propylenedioxythiophene Conjugated Polymer As Hole Transport Layer For Efficient And Stable Perovskite Solar Cells, Yuanhao Tang, Ke Ma, Wenhao Shao, Yoon Ho Lee, Ashkan Abtahi, Jiaonan Sun, Hanjun Yang, Aidan H. Coffey, Harindi R. Atapattu, Mustafa Ahmed, Qixuan Hu, Wenzhan Xu, Raunak Dani, Limei Wang, Chenhui Zhu, Kenneth R. Graham, Jianguo Mei, Letian Dou

Chemical and Materials Engineering Faculty Publications

Despite the outstanding electric properties and cost-effectiveness of poly- (3,4-ethylenedioxythiophene) (PEDOT) and its derivatives, their performance as hole transport layer (HTL) materials in conventional perovskite solar cells (PSCs) has lagged behind that of widely used spirobifluorene-based molecules or poly(triaryl amine). This gap is mainly from their poor solubility and energy alignment mismatch. In this work, the design and synthesis of a pyrrole-modified HTL (PPr) based on 3,4-propylenedioxythiophene (ProDOT) are presented for efficient and stable PSCs. As a result of the superior defects passivation ability, excellent contact with perovskite, enhanced hole extraction, and high hydrophobicity, the unencapsulated PPr-based PSCs showed the …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Pulsing-Induced Healing Of A Surface Crack Of A Nickel-Based Alloy, Liwei Wang, Mingming Quan, Zhen Tan, Ming Liu, Dianlong Wang, Xiao Yang, Ying Liu, Yaning Mao, Zhimin Liang, Fuqian Yang

Chemical and Materials Engineering Faculty Publications

In this work, we demonstrate the feasibility of applying electric pulses to heal surface cracks on nickel-based alloy GH4169 under compressive load. There exists an incubation time for the onset of the healing of a crack, which is associated with local temperature at the crack tip. The crack size decreases with increasing the pulsing time at a constant healing rate prior to complete healing of the crack. Increasing compressive load accelerates the healing process. The electric pulsing leads to the formation of an influential zone surrounding the crack with the finest grain sizes in the healed crack and the coarsest …

Spontaneous Alignment Of Myotubes Through Myogenic Progenitor Cell Migration, Lauren E. Mehanna, Adrianna R. Osborne, Charlotte A. Peterson, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

In large-volume muscle injuries, widespread damage to muscle fibers and the surrounding connective tissue prevents myogenic progenitor cells (MPCs) from initiating repair. There is a clinical need to rapidly fabricate large muscle tissue constructs for integration at the site of large volume muscle injuries. Most strategies for myotube alignment require microfabricated structures or prolonged orientation times. We utilize the MPC’s natural propensity to close gaps across an injury site to guide alignment on collagen I. When MPCs are exposed to an open boundary free of cells, they migrate unidirectionally into the cell-free region and align perpendicular to the original boundary …

Development Of Iron Oxide Nanozyme For Cancer Therapy, Zhongchao Yi

Theses and Dissertations--Biomedical Engineering

Cancer therapies that leverage reactive oxygen species (ROS) have shown potential for cancer inhibition due to their ability to induce oxidative stress in tumor cells. Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for ROS-dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs has been a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions in this work. The results show that wüstite (Fe_1-xO) nanoparticles exhibit higher catalytic activity …

Development Of Glutathione-Responsive Disulfide-Containing Poly(Beta-Amino Esters) With Varied Hydrophilicity And Acrylate Functionality, Anastasiia Aronova

Theses and Dissertations--Chemical and Materials Engineering

Smart biomaterials are becoming promising for therapeutic deliveries due to their ability to respond to changes in the environment. Redox-responsive hydrogels are a promising type of smart polymer that can swell and degrade according to cellular oxidative stress levels. Glutathione, abundant in cells, is crucial in redox-responsive biomaterials, serving as a key reactive molecule. This study explored the degradation kinetics of glutathione-responsive poly(β-amino ester) (PBAE) polymers created through a single-step Michael addition. We examined how disulfide content influences the degradation kinetics of these PBAE networks. Additionally, we investigated how the hydrophilicity and functionality of acrylate affect the degradation of disulfide-containing …

Sustained Release Systems For Endometrial Cancer, Claire E. Rowlands

Theses and Dissertations--Chemical and Materials Engineering

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is the most common cancer of female reproductive organs. From 2007-2016 there has been a global rise in incidence of EC of 1.3 %. Typically, EC is treated with surgery, but at later stages surgery is less effective requiring chemotherapy and/or radiation therapy. These treatment options are less effective than surgery and there are very few FDA approved chemotherapies for EC. The minuscule number of effective treatment options as well as an increase in incidence shows the need for creating improved treatments for EC. There has been …

Advanced Microstructural Characterization Of Functionally Graded Dental Ceramic Material For Materials-Informed Finishing, Angani Vigneswaran

Theses and Dissertations--Manufacturing Systems Engineering

Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) has gained popularity as the choice of material for dental prosthetics. Ivoclar Vivadent’s IPS e.max ZirCAD Prime dental ceramic incorporates a unique gradient technology that varies the yttria content over the thickness of the material. The top layer is composed of 5Y-TZP which is desired for its optical properties while the bottom layer is composed of a much stronger 3Y-TZP. In between the two layers, 5Y-TZP and 3Y-TZP are mixed to form a transition layer. Varying the amount of yttria allows for more esthetically pleasing translucency in the visible areas of the restoration without compromising …

3-Dimensional Muscle Constructs: Using Hydrogels In Order To Model The Effects Of Exercise In Disease Conditions, Mark Mchargue

Theses and Dissertations--Biomedical Engineering

Currently, there is no standard in vitro model for studying the effects of mechanical stimulation on muscle in type II diabetes. Existing models primarily utilize electrical stimulation, which does not fully recapitulate the effects of exercise. In this thesis, we create a standardized in vitro model of murine muscle that can recapitulate the benefits seen in exercise when mechanically stimulated. Moreover, we show that a type II diabetes environment has similar effects on the muscle in vitro as well as in vivo.

Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna

Theses and Dissertations--Chemical and Materials Engineering

Volumetric muscle loss (VML) remains one of the few skeletal muscle injuries without a reliable and repeatable treatment. In large volume muscle injuries, muscle fibers as well as the surrounding connective tissue are damaged, preventing therapeutic muscle stem cells, called myogenic progenitor cells (MPCs), from reaching the injury site and initiating repair. There is a clinical need to rapidly fabricate in vitro muscle tissue constructs that mimic the native tissue organization, with aligned myotubes, for insertion and integration at the patient’s injury site. In this dissertation, we utilize the MPC’s natural propensity to close gaps across an injury site to …

An Electrochemical, Fluidic, Chip-Based Biosensor For Biomarker Detection, Lauren Bell

Theses and Dissertations--Biomedical Engineering

Biosensors and their use in both the research and clinical field for the detection and monitoring of critical biomarkers are prevalent and constantly improving. However, continued research needs to be done to address shortcomings, such as low sensitivity, poor specificity, and poor readiness for integration into research use and patient care. The objective of this research was to create a combined fluidic, chip-based biosensor that could detect different biomarkers with high sensitivity and ease of use. For assessing the developed sensor, three separate biomarkers were tested: glucose, cholesterol, and oxygen. Both the glucose biosensor and cholesterol biosensor were combined with …

Tailoring Texture, Microstructure, And Shape Memory Behavior Of Niti Alloys Fabricated By L-Pbf-Am, Sayed Ehsan Saghaian N.E.

Theses and Dissertations--Mechanical and Aerospace Engineering

Laser Powder Bed Fusion (L-PBF) is one of the most promising Additive Manufacturing (AM) methods to fabricate near net-shape metallic materials for a wide range of applications such as patient-specific medical devices, functionally graded materials, and complex structures. NiTi shape memory alloys (SMAs) are of great interest due to a combination of unique features, such as superelasticity, shape memory effect, high ductility, work output, corrosion resistance, and biocompatibility that could be employed in many applications in automotive, aerospace, and biomedical industries. Due to the difficulties with traditional machining and forming of NiTi components, the ability to fabricate complex parts, tailor …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Bacterial Cell Wall Characterization Via Atomic Force And Confocal Microscopy, Joree Sandin

Theses and Dissertations--Mechanical and Aerospace Engineering

Poor oral hygiene is a severe global health issue, with about 44% of the Earth’s population suffering from untreated tooth decay, accounting for over $100 billion dollars spent on dental services per year in the United States, alone. Manual treatments, such as brushing, flossing, or swishing with antiseptic rinse are the main ways to alleviate harmful bacteria that cause these oral health problems. Streptococcus mutans (S. mutans) is a group of highly antibiotic, Gram-positive bacteria that heavily contribute to oral cavities, plaque build-up, and potential loosening or loss of dental implants if a biofilm develops. Currently, the mechanism …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Cell Surface Coatings For Mammalian Cell-Based Therapeutic Delivery, Pei-Jung Wu

Theses and Dissertations--Chemical and Materials Engineering

The cell plasma membrane is an interactive interface playing an important role in regulating cell-to-cell, cell-to-tissue contact, and cell-to-environment responses. This environment-responsive phospholipid layer consisting of multiple dynamically balanced macromolecules, such as membrane proteins, carbohydrate and lipids, is regarded as a promising platform for various surface engineering strategies. Through different chemical modification routes, we are able to incorporate various artificial materials into the cell surface for biomedical applications in small molecule and cellular therapeutics.

In this dissertation, we establish two different cell coating techniques for applications of cell-mediated drug delivery and the localization of cell-based therapies to specific tissues. The …

Synthesis And Characterization Of Blue Light Poly(Β-Amino Ester)S, Nicholas John Kohrs

Theses and Dissertations--Biomedical Engineering

Volumetric muscle loss (VML) is a debilitating injury which results in full or partial loss of function. Current clinical options utilize tissue grafts and bracing to restore function. Tissue graft implantation oftentimes leads to serious complications, some of which end in graft rejection and thereby necessitate further surgeries and procedures. Polymeric scaffolds show promise as scaffolding systems due to their mechanical properties and overall degradation profiles. Scaffolds need appropriate mechanical properties, 10-60 kPa modulus, and overall degradation times, five days to two weeks, to initiate tissue regeneration. Poly(β-amino ester)s (PBAE), a class of synthetic polymers, act as a safe biocompatible …

Toxicity Evaluation Of Magnetic Hyperthermia Induced By Remote Actuation Of Magnetic Nanoparticles In 3d Micrometastasic Tumor Tissue Analogs For Triple Negative Breast Cancer, Nathanael A. Stocke, Pallavi Sethi, Amar Jyoti, Ryan Chan, Susanne M. Arnold, J. Zach Hilt, Meenakshi Upreti

Chemical and Materials Engineering Faculty Publications

Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. …

Synthesis And Characterization Of Poly(Simvastatin) - Incorporated Copolymers And Blends For Bone Regeneration, Theodora Asafo-Adjei

Theses and Dissertations--Biomedical Engineering

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release.

Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) …

Shape Memory Behavior Of Dense And Porous Niti Alloys Fabricated By Selective Laser Melting, Soheil Saedi

Theses and Dissertations--Mechanical and Aerospace Engineering

Selective Laser Melting (SLM) of Additive Manufacturing is an attractive fabrication method that employs CAD data to selectively melt the metal powder layer by layer via a laser beam and produce a 3D part. This method not only opens a new window in overcoming traditional NiTi fabrication problems but also for producing porous or complex shaped structures. The combination of SLM fabrication advantages with the unique properties of NiTi alloys, such as shape memory effect, superelasticity, high ductility, work output, corrosion, biocompatibility, etc. makes SLM NiTi alloys extremely promising for numerous applications.

The SLM process parameters such as laser power, …

Pore-Confined Carriers And Biomolecules In Mesoporous Silica For Biomimetic Separation And Targeting, Shanshan Zhou

Theses and Dissertations--Chemical and Materials Engineering

Selectively permeable biological membranes composed of lipophilic barriers inspire the design of biomimetic carrier-mediated membranes for aqueous solute separation. This work imparts selective permeability to lipid-filled pores of silica thin film composite membranes using carrier molecules that reside in the lipophilic self-assemblies. The lipids confined inside the pores of silica are proven to be a more effective barrier than bilayers formed on the porous surface through vesicle fusion, which is critical for quantifying the function of an immobilized carrier. The ability of a lipophilic carrier embedded in the lipid bilayer to reversibly bind the target solute and transport it through …

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 …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

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 …

Synthesis And Characterization Of Antioxidant Conjugated Poly(Βeta-Amino Ester) Micro/Nanogels For The Suppression Of Oxidative Stress, Prachi Gupta

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS), which can result in the growth arrest of cells followed by cell disintegration or necrosis. A number of small molecule antioxidants (e.g. curcumin, quercetin and resveratrol) are capable of directly scavenging ROS, thereby short-circuiting the self-propagating oxidative stress state. However, poor solubility and rapid 1^st pass metabolism results in overall low bioavailability and acts as a barrier for its use as a drug to suppress oxidative stress efficiently.

To overcome this limitation, these small molecule antioxidants were covalently conjugated into poly(β-amino ester) (PβAE) …

Biomimetic Oral Mucin From Polymer Micelle Networks, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated …

Layered, Flexible Drug Delivery Films For The Prevention Of Fibrotic Scar Tissue Formation, Cheryl L. Rabek

Theses and Dissertations--Biomedical Engineering

Open wounds account for about 50% of military injuries and 10% of non‐fatal traffic injuries. Scar tissue formation in these wounds may be reduced or prevented if treated with a combination of molecules whose release is tuned to the healing phases. The goal of this research was to develop flexible, layered drug delivery films for sequential, localized release of anti‐inflammatory, anti‐oxidant, and anti‐fibrotic molecules to soft tissue.

Films were composed of cellulose acetate phthalate (CAP) and Pluronic F‐127 (Pluronic). To impart flexibility, plasticizers, triethyl citrate (TEC) or tributyl citrate (TBC), were added. Mechanical analysis was performed on films as prepared …

A Local, Sustained Delivery System For Zoledronic Acid And Rankl-Inhibitory Antibody As A Potential Treatment For Metastatic Bone Disease, Rohith Jayaram

Theses and Dissertations--Biomedical Engineering

Cancerous solid tumors can migrate and lead to metastatic bone disease. Drugs prescribed to reduce bone resorption from metastasis, such as zoledronic acid and the RANKL-inhibitory antibody Denosumab, cause side effects such as osteonecrosis of the jaw when delivered systemically. This project used two biocompatible materials, acrylic bone cement (PMMA) and poly(lactic-co-glycolic acid) (PLGA), to incorporate and sustain release of anti-resorptive agents. Results showed similar mechanical properties for acrylic bone cements loaded up to 6.6% drug by weight. Results showed sustained zoledronic acid release for 8 weeks from both systems, with PMMA releasing up to 22% of loaded drug and …