Biochemical and Biomolecular Engineering Commons^™

Raman Spectroscopic Analysis Of Fingernail Clippings Can Help Differentiate Between Postmenopausal Women Who Have And Have Not Suffered A Fracture, James R. Beattie, Niamh M. Cummins, Clare Caraher, Olive M. O'Driscoll, Aruna T. Bansal, Richard Eastell, Stuart H. Ralston, Michael D. Stone, Gill Pearson, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Raman spectroscopy was applied to nail clippings from 633 postmenopausal British and Irish women, from six clinical sites, of whom 42% had experienced a fragility fracture. The objective was to build a prediction algorithm for fracture using data from four sites (known as the calibration set) and test its performance using data from the other two sites (known as the validation set). Results from the validation set showed that a novel algorithm, combining spectroscopy data with clinical data, provided area under the curve (AUC) of 74% compared to an AUC of 60% from a reduced QFracture score (a clinically accepted …

Local Delivery Of Ctla-4 Blockade Inhibits Growth Of Pancreatic Tumors, Jack Baltz

Biomedical Engineering Undergraduate Honors Theses

Immune checkpoint blockade has demonstrated great potential in activating antitumor immunity. Ipilimumab is a monoclonal antibody which targets cytotoxic T-lymphocyte antigen-4. CTLA-4 belongs to the CD28 class of receptors and is found on the surface of CD4⁺ and CD8⁺ T cells. CTLA-4 acts to suppress the immune system when bound to CD80 and CD86 receptors on antigen presenting cells. Ipilimumab, or anti-CTLA-4, has shown to be effective in significantly extending the survival of patients with metastatic melanoma. However, systemic delivery of Ipilimumab also induces significant side effects such as: colitis, dermatitis, uveitis, and hypophysitis. In order to minimize …

Sustained Cell Differentiation Of 2d H9 Human Embryonic Stem Cells Into Mesenchymal Stem Cells, Hannah M. Christian

UCARE: Research Products

This experiment consisted of the controlled differentiation of H9 embryonic stem cells to mesenchymal stem cells. Though this experiment was repeated twice and improvement was seen in these repetitions, the cells were only able to be partially differentiated. However, the morphology of the differentiated cells is similar to those of healthy adult mesenchymal stem cells.

The progression of the differentiation can be seen in the microscope slide photos below. Throughout the differentiation, there occurred a decrease in cell survival and reduction of cell growth, but an increase in mesenchymal stem cell morphology. Throughout the last week of the differentiation, very …

Brain Tumor In A Dish: Glioma/Astrocyte Co-Cultures As A Model For In Vitro Studies, Erin Eickman, Christina Wilson, Srivatsan Kidambi

UCARE: Research Products

This study seeks to engineer an in vitro co-culture model to elucidate the role of glioma-astrocyte interactions on molecular changes in the tumor microenvironment. The use of patterned co-cultures created with polyelectrolyte multilayers and micromolding in capillaries will allow tthe investigation of cell-cell communication. This study will lead to better understanding of the role of healthy cells in cancer progression and potential treatment options.

The Role Of Poly(Acrylic Acid) In Conventional Glass Polyalkenoate Cements, Adel M.F. Alhalawani, Declan J. Curran, Daniel Boyd, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Glass polyalkenoate cements (GPCs) have been used in dentistry for over 40 years. These novel bioactive materials are the result of a reaction between a finely ground glass (base) and a polymer (acid), usually poly (acrylic acid) (PAA), in the presence of water. This article reviews the types of PAA used as reagents (including how they vary by molar mass, molecular weight, concentration, polydispersity and content) and the way that they control the properties of the conventional GPCs (CGPCs) formulated from them. The article also considers the effect of PAA on the clinical performance of CGPCs, including biocompatibility, rheological and …

Characterization Of Silica-Based And Borate-Based, Titanium-Containing Bioactive Glasses For Coating Metallic Implants, Omar Rodriguez, Declan J. Curran, Marcello Papini, Lana M. Placek, Anthony W. Wren, Emil H. Schemitsch, Paul Zalzal, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Bioactive glasses have found applications in diverse fields, including orthopedics and dentistry, where they have been utilized for the fixation of bone and teeth and as scaffolds for drug delivery. The present work outlines the characterization of two novel titanium-containing glass series, one silica-based and one borate-based. For the silica-based series, titanium is added at the expense of silicon dioxide whereas for the borate-based series, it is added at the expense of boron oxide as confirmed by Energy Dispersive Spectroscopy. Amorphous structures are obtained for silica-based glass at 15 mol% TiO₂ and for borate-based glasses at 0 mol% and …

Gallium-Containing Mesoporous Bioactive Glass With Potent Hemostatic Activity And Antibacterial Efficacy, Sara Pourshahrestani, Ehsan Zeimaran, Nahrizul Adib Kadri, Nicola Gargiulo, Shani Samuel, Sangeetha Vasudevaraj Naveen, Tunku Kamarul, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga⁺³) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop …

Relating Ion Release And Ph To In Vitro Cell Viability For Gallium-Inclusive Bioactive Glasses, Timothy J. Keenan, L. M. Placek, T. L. Mcginnity, Mark R. Towler, M. M. Hall, A. W. Wren

Chemical and Biochemical Engineering Faculty Research & Creative Works

A bioactive glass (BG) in which Ga was substituted for Zn was formulated to investigate whether the ionic form of Ga can elicit effects similar to gallium nitrate. The ion release and pH of BG extracts were evaluated, as well as the in vitro cytocompatibility of extracts in contact with mouse fibroblasts and human osteoblasts. After incubation times of 1 year, the glass (TGa-1) containing the smaller Ga-addition (8 mol%) released the most sodium (Na) (1420 mg/L), silicon (Si) (221 mg/L), and Ga (1295 mg/L), while the glass (TGa-2) containing the larger Ga-addition (16 mol%), exhibited release levels between TGa-1, …

Antibacterial Properties Of Poly (Octanediol Citrate)/Gallium-Containing Bioglass Composite Scaffolds, Ehsan Zeimaran, Sara Pourshahrestani, Ivan Djordjevic, Belinda Pingguan-Murphy, Nahrizul Adib Kadri, Anthony W. Wren, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Bioactive glasses may function as antimicrobial delivery systems through the incorporation and subsequent release of therapeutic ions. The aim of this study was to evaluate the antimicrobial properties of a series of composite scaffolds composed of poly (octanediol citrate) with increased loads of a bioactive glass that releases zinc (Zn²⁺) and gallium (Ga³⁺) ions in a controlled manner. The antibacterial activity of these scaffolds was investigated against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated …

Inorganic Hemostats: The State-Of-The-Art And Recent Advances, Sara Pourshahrestani, Ehsan Zeimaran, Ivan Djordjevic, Nahrizul Adib Kadri, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Hemorrhage is the most common cause of death both in hospitals and on the battlefield. The need for an effective hemostatic agent remains, since all injuries are not amenable to tourniquet use. There are many topical hemostatic agents and dressings available to control severe bleeding. This article reviews the most commonly used inorganic hemostats, subcategorized as zeolite and clay-based hemostats. Their hemostatic functions as well as their structural properties that are believed to induce hemostasis are discussed. The most important findings from in vitro and in vivo experiments are also covered.

Noninvasive Measurement Of Electrical Events Associated With A Single Chlorovirus Infection Of A Microalgal Cell, Seung-Woo Lee, Eun-Hee Lee, Gerhard Thiel, James L. Van Etten, Ravi Saraf

Department of Chemical and Biomolecular Engineering: Faculty Publications

Chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains a viral-encoded K⁺ channel imbedded in its internal membrane, which triggers host plasma membrane depolarization during virus infection. This early stage of infection was monitored at high resolution by recording the cell membrane depolarization of a single Chlorella cell during infection by a single PBCV-1 particle. The measurement was achieved by depositing the cells onto a network of one-dimensional necklaces of Au nanoparticles, which spanned two electrodes 70 μm apart. The nanoparticle necklace array has been shown to behave as a single-electron device at room temperature. The resulting electrochemical field-effect transistor …

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) …

Raman Spectroscopy Applied To The Noninvasive Detection Of Monosodium Urate Crystal Deposits, Declan J. Curran, Laurence Rubin, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

An off-the-shelf Raman Spectrometer (RS) was used to noninvasively determine the presence of monosodium urate (MSU) crystals on the metatarsophalangeal joint (MTPJ) of a single gout sufferer. The spectrum sourced from the clinically diagnosed gout sufferer was compared to that sourced from an age-matched healthy subject scanned using the same protocol. Minimal signal processing was conducted on both spectra. Peaks characteristic of MSU crystals were evident on the spectrum sourced from the gout sufferer and not on the spectrum from the healthy control.

A Novel Synthetic Yeast For Enzymatic Biodigester Pretreatment, Tianyu Tan, Mark S. Aronson, Arren Liu, Jill H. Osterhus, Melissa Robins, Suraj Mohan, Erich Leazer, Bowman Clark, Alexa Petrucciani, Katherine Lowery, James Welch, Casey Martin, Helena Lysandrou, Michael E. Scharf, Jenna Rickus

The Summer Undergraduate Research Fellowship (SURF) Symposium

Lignin, a complex organic polymer, is a major roadblock to the efficiency of biofuel conversion as it both physically blocks carbohydrate substrates and poisons biomass degrading enzymes, even if broken down to monomer units. A pretreatment process is often applied to separate the lignin from biomass prior to biofuel conversion. However, contemporary methods of pretreatment require large amounts of energy, which may be economically uncompelling or unfeasible. Taking inspiration from several genes that have been isolated from termites and fungi which translate to enzymes that degrade lignin, we want to establish a novel “enzymatic pretreatment” system where microbes secrete these …

Development Of A Novel Enzymatic Pre-Treatment For Lignocellulosic Biomass, Melissa Robins, Jenna Rickus

The Summer Undergraduate Research Fellowship (SURF) Symposium

Biofuels, fuels derived directly from living matter, present a renewable and environmentally friendly alternative to petroleum based fuels. Bioethanol produced from low input energy crops or agricultural waste is a promising fuel source because it does not interfere with the human food supply chain and the ethanol produced can be blended with gasoline. These potential sources of bioethanol are not yet commercially viable due to a polymer called lignin present in the plant’s cell wall which impedes the conversion of cellulose to glucose and the eventual fermentation of glucose to ethanol. Developing new methods for the pretreatment of lignocellulosic biomass …

Silver Nanoparticle Coated Bioactive Glasses - Composites With Dex/Cmc Hydrogels: Characterization, Solubility, And In Vitro Biological Studies, Anthony W. Wren, Pegah Hassanzadeh, Lana M. Placek, Timothy J. Keenan, Aisling Coughlan, Lydia R. Boutelle, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Silver (Ag) coated bioactive glass particles (Ag-BG) were formulated and compared to uncoated controls (BG) in relation to glass characterization, solubility and microbiology. X-ray diffraction (XRD) confirmed a crystalline AgNP surface coating while ion release studies determined low Ag release (/L). Cell culture studies presented increased cell viability (127 and 102%) with lower liquid extract (50 and 100 ml/ml) concentrations. Antibacterial testing of Ag-BG in E. coli, S. epidermidis and S. aureus significantly reduced bacterial cell viability by 60-90%. Composites of Ag-BG/CMC-Dex Hydrogels were formulated and characterized. Agar diffusion testing was conducted where Ag-BG/hydrogel composites produced the largest inhibition zones …

Bioactive Glass Reinforced Elastomer Composites For Skeletal Regeneration: A Review, Ehsan Zeimaran, Sara Pourshahrestani, Ivan Djordjevic, Belinda Pingguan-Murphy, Nahrizul Adib Kadri, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Biodegradable elastomers have clinical applicability due to their biocompatibility, tunable degradation and elasticity. The addition of bioactive glasses to these elastomers can impart mechanical properties sufficient for hard tissue replacement. Hence, a composite with a biodegradable polymer matrix and a bio glass filler can offer a method of augmenting existing tissue. This article reviews the applications of such composites for skeletal augmentation.

Effects Of Strontium Substitution On Bioactivity Of Hydroxyapatite, Chokchai Yatongchai, Lana M. Placek, Mark R. Towler, Anthony W. Wren

Chemical and Biochemical Engineering Faculty Research & Creative Works

Effect of strontium (Sr) substitution on bioactivity of hydroxyapatite (HA) was investigated. The substitution of Sr²⁺ for Ca²⁺ in the HA lattice increases biodegradability of Sr-substituted HA (Sr-HA) and accelerates the formation of apatite crystals on the Sr-HA surface. Moreover, the dissolution products from HA and Sr-HA samples are not cyto-toxic.

Characterization Of Novel Chitosan/Polyelectrolyte Nanoparticles, Michaela Wynne Mertz

Biomedical Engineering Undergraduate Honors Theses

Chitosan-based nanoparticles are under investigation as delivery vehicles for drugs, genes, and proteins. Due to the biocompatibility, mucoadhesive nature, and biodegradable nature of chitosan and binding qualities, anionic nature, and biocompatible qualities of heparin, chitosan/heparin nanoparticles (CHNPs) are a promising platform for the delivery of labile proteins. However, the literature lacks a definitive process to control the size, efficiency, and yield of CHNPs at higher concentrations of reagents. Additionally there is a need to improve loading efficiency of CHNPs. In this study CHNPs have been synthesized and characterized for size, yield, protein loading efficiency, and release. The CHNPs were prepared …

Evaluating The Viability Of Graphene Oxide For The Removal Of Ni(Ii) Ions From Waste Water, Cale M. White

Biomedical Engineering Undergraduate Honors Theses

When levels of heavy metal ions such as nickel (Ni), copper (Cu), lead (Pb), Zinc (Zn), and Cobalt (Co) exceed the tolerance values for industrial wastewater, it can devastate the environment as well as the health of the individuals consuming the water. Heavy metal ions are not biodegradable and will accumulate in organic matter.(1) This accumulation leads to toxic levels in the blood and hence damage to nerve tissue, kidneys, the liver, and other vital organs. (2) Effective removal processes of these heavy metals from water must be developed. This study explores a method to adsorb nickel from water with …

Fractionation Of Chitosan Using A Novel Precipitation Method, Davis J. Ward

Biomedical Engineering Undergraduate Honors Theses

Chitosan is a derivative of chitin, a biopolymer found in the exoskeletons of crustaceans. Chitosan is under heavy investigation in the field of drug delivery due to its wide versatility. One such delivery mechanism is the use of hydrogels in cancer immunotherapy delivery. The viscosity of chitosan in its use as a hydrogel depends on the length of chitosan’s N-acetyl D-glucosamine chains, which in turn determines the molecular weight of chitosan. Because there is such a wide range of viscosity in a typical sample of chitosan, there is a need for a simple technique to fractionate the chitosan based on …

The Investigation Of Chitosan-Based Hydrogels For Intratumoral Delivery Of Immunotherapeutic Cytokines, Ethan Drew Lowry

Biomedical Engineering Undergraduate Honors Theses

Controlled and localized delivery of Interleukin 12 (IL-12) is critical to effective and non-toxic cancer immunotherapy. Current delivery protocols for pre-clinical anti-tumor trials utilize solutions of chitosan, a mucoadhesive and bioeliminable biopolymer, to slow the release of IL- 12 into the tumor microenvironment. In order to further increase IL-12 retention, we have developed and characterized two chitosan-based in situ gelling hydrogels for IL-12 immunotherapy. One hydrogel, composed of heparin and chitosan, is herein described from initial conception through multiple stages of characterization including isolation of a range of suitable hydrogel formulations and observational physical and chemical properties. A second hydrogel …

Fluorescent Imaging On A Microfluidics Chip For Quantification Of Leukocyte Count, Aneeka Majid

Biomedical Engineering Undergraduate Honors Theses

We have demonstrated a method for conducting a leukocyte count in whole blood using a microfluidics chip and epi-fluorescence setup. Leukocyte counts provide physicians with a wealth of information about a patient’s medical condition and as such are routinely completed for many hospital visits. Miniaturization of this diagnostic tool may enable physicians to provide healthcare in resource-limited settings, where patients would otherwise not receive this test. The microfluidics chip was fabricated in polydimethylsiloxane (PDMS) using soft-film lithography. Following further processing and cleaning, the PDMS mold is exposed to UV-ozone for surface activation, and then sealed with a glass coverslip to …

Monitoring The Effects Of Mmp Inhibitors On Extracellular Matrix Degradation For Use In Implant Protection, Jake D. Jones

Biomedical Engineering Undergraduate Honors Theses

In order to lengthen the functional time of implantable ECM, the mechanism of degradation must be inhibited. The matrix metalloproteases are the primary method by which ECM is broken down, and the TIMP family of proteins exists as proof that inhibition of these proteases is possible naturally. In particular, the glycoprotein TIMP-1 plays an inhibitory role with most of the MMPs including the collagenases. Furthermore, there exist synthetic or chemical molecules that likewise inhibit the catalytic actions of MMPs. One such molecule is Batimastat (BB-94) which has been proven to be a dose dependent inhibitor of MMPs during the inflammatory …

Development Of An In Vitro Myogenesis Assay, Anna Arnaud

Biomedical Engineering Undergraduate Honors Theses

The objective of this study was to explore the interaction between mouse C2C12 cells and the extracellular matrix, particularly the process of myoblasts converting to myocytes. This study aimed to create a myogenesis assay that presents a process to effectively monitor the development of mouse C2C12 myoblasts into differentiated skeletal myotubes through detection of the protein MyoD. Myogenesis, the development of muscle tissue, occurs when muscle progenitor cells, myoblasts, fuse to form multinucleated myotubes, followed by cell fusion and resulting in a myofiber capable of contraction. An in vitro myogenesis assay would enable further research to efficiently test the effect …

Multiplexed Microfluidic Loop-Mediated Isothermal Amplification Of The 16s Rrna Gene For The Diagnosis Of Neonatal Sepsis In Resource-Limited Environments, Griffin Thomas Sonaty

Biomedical Engineering Undergraduate Honors Theses

Bacterial infection, or sepsis, places a disproportionately high burden on newborns in developing countries. This is due in part to a lack of diagnostic tools suitable for sustainable use in resource-limited nurseries. One potential vehicle for a new diagnostic assay is loop-mediated isothermal amplification (LAMP), a high-yield DNA amplification method. LAMP has been used to detect single genes from bacteria in blood serum samples to aid in sepsis diagnosis. While specific, this approach can only provide detection for one species at a time. LAMP could be adapted to detect a broader set of bacteria, while retaining a degree of specificity …

Intracellular Uptake Of Chitosan Nanoparticle-Based Vaccines, Katherine E. Wilson

Biomedical Engineering Undergraduate Honors Theses

Particle-based delivery systems are a promising approach to enhance antigen-specific immunity for use in vaccines. Chitosan, a natural polysaccharide derived from the exoskeletons of crustaceans, shows great potential as a vaccine carrier due to its favorable properties as a biomaterial, including biocompatibility and biodegradability. In this study, the intracellular uptake of chitosan nanoparticles is explored and compared to that of other commonly used particle-based delivery vehicles, such as poly (lactic-co-glycolic acid) (PLGA). Fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) was used as a model protein antigen and encapsulated in both chitosan particles via precipitation-coacervation and PLGA particles via double emulsion solvent …

Fabrication And Characterization Of Poly(Octanediol Citrate)/Gallium-Containing Bioglass Microcomposite Scaffolds, Ehsan Zeimaran, Sara Pourshahrestani, Belinda Pingguan-Murphy, Nahrizul Adib Kadri, Hussin A. Rothan, Rohana Yusof, Mark R. Towler, Ivan Djordjevic

Chemical and Biochemical Engineering Faculty Research & Creative Works

Bone can be affected by osteosarcomae requiring surgical excision of the tumor as part of the treatment regime. Complete removal of cancerous cells is difficult and conventionally requires the removal of a margin of safety around the tumor to offer improved patient prognosis. This work considers a novel series of composite scaffolds based on poly (octanediol citrate) (POC) impregnated with gallium-based bioglass microparticles for possible incorporation into bone following tumor removal. The objective of this research was to fabricate and characterize these scaffolds and subsequently report on their mechanical and biological properties. The porous micro composite scaffolds with various concentrations …

A Glass Polyalkenoate Cement Carrier For Bone Morphogenetic Proteins, Adel M.F. Alhalawani, Omar Rodriguez, Declan J. Curran, Russell Co, Sean Kieran, Saad Arshad, Timothy J. Keenan, Anthony W. Wren, Gazelle Crasto, Sean A.F. Peel, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

This work considers a glass polyalkenoate cement (GPC)-based carrier for the effective delivery of bone morphogenetic proteins (BMPs) at an implantation site. A 0.12 CaO–0.04 SrO–0.36 ZnO–0.48 SiO₂ based glass and poly(acrylic acid) (PAA, Mw 213,000) were employed for the fabrication of the GPC. The media used for the water source in the GPC reaction was altered to produce a series of GPCs. The GPC liquid media was either 100 % distilled water with additions of albumin at 0, 2, 5 and 8 wt% of the glass content, 100 % formulation buffer (IFB), and 100 % BMP (150 µg …

Investigating The Solubility And Cytocompatibility Of Cao-Na2o-Sio2/Tio2 Bioactive Glasses, Anthony W. Wren, Aisling Coughlan, Courtney M. Smith, Sarah P. Hudson, Fathima R. Laffir, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

This study aims to investigate the solubility of a series of titanium (TiO₂)-containing bioactive glasses and their subsequent effect on cell viability. Five glasses were synthesized in the composition range SiO₂-Na₂O-CaO with 5 mol % of increments TiO₂ substituted for SiO₂. Glass solubility was investigated with respect to (1) exposed surface area, (2) particle size, (3) incubation time, and (4) compositional effects. Ion release profiles showed that sodium (Na⁺) presented high release rates after 1 day and were unchanged between 7 and 14 days. Calcium (Ca²⁺) release …