Biomedical Engineering and Bioengineering Commons^™

Interaction Of Fibrinogen With Fibronectin: Purification And Characterization Of A Room Temperature-Stable Fibrinogen-Fibronectin Complex From Normal Human Plasma, Ayman E. Ismail

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

A fibrinogen-fibronectin complex (γγ’pdFI-pdFN) was purified from normal human plasma using a sequence of cryoprecipitation, ammonium sulfate fractionation, and DEAE Sepharose chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing condition showed both a 1:1 stoichiometric ratio of fibrinogen (FI) to fibronectin (FN) as well as a stoichiometric ratio of 1:1 of γg to gγ’. The γγ’pdFI-pdFN complex was non-covalent in nature as it was disrupted by affinity adsorption to Gelatin Sepharose where pdFN bound strongly and the disrupted γγ’pdFI fell through the chromatographic column. Surprisingly, the purified γγ’pdFI-pdFN complex was more broadly thermally stable than plasma FI (pdFI) …

Customization Of Titanate Nanofiber Bioscaffolds, Jared Hopkins

Biomedical Engineering Undergraduate Honors Theses

In the field of orthopedic devices implant loosening is a major issue resulting in the majority of device failures. These failures result in the need for costly secondary procedures. To reduce device loosening an improved method of tissue anchoring is required. A previously studied titanate nanofiber bioscaffold has been shown to be safely implantable and to contribute to the differentiation of mesenchymal stem cells to osteocytes. Through the customization of both physical and chemical characteristics this titanate nanofiber bioscaffold was fabricated as a potential means to enhance tissue anchoring for use with orthopedic devices. This customization was enabled by acoustic …

Investigating The Mechanical Behaviors Of Organic/Inorganic Composite Bone Scaffolds, Parker Davidson

Biomedical Engineering Undergraduate Honors Theses

The regeneration of bone over a large area cannot occur without a structure for the bone cells to bind and divide. The use of an organic/inorganic composite bone scaffold appears to be a promising alternative to the current clinical standard of bone grafting. Bone grafting is very limited, in that the size and shape of the area are hard to replicate and the use of donor tissue can trigger an immunologic response resulting in rejection of the bone tissue. This study experimented with composite bone scaffolds which can be made to fit the shape of the area in which bone …

Bending Stiffness In Cadaveric And Composite Long Bones Following Total Joint Replacement, Danielle Gehron, Anderson Adams Ms, Tatsuya Sueyoshi Md, Scott R. Small Ms

Rose-Hulman Undergraduate Research Publications

Several biomechanics studies have utilized commercially available replicate bone models as an alternative to cadaveric tissue specimens, in part due to their ease of handling and reduced expense. In an effort to validate the use of replicate bone specimens in biomechanics research, a number of studies have compared material properties of whole tibia and femur specimens to those of similar cadaveric specimens. Many of these validation studies have ascertained that the material properties of whole bone composite models fall within the range of those properties of cadaveric specimens, while offering reduced interspecimen variability. Current literature lacks, however, the direct comparison …

Patterned Alginate Hydrogels To Induce Chondrocyte Alignment, Jordan Catherine Verplank, Taylor D. Laughlin, Angela K. Pannier

UCARE: Research Products

The growth plate has an intricate architecture, and this architecture is necessary for directional growth of bones. Specifically, the cells align in longitudinal columns. As the growth plate expands with this pattern, the bone elongates with the same alignment pattern. The purpose of this research is to mimic this single celled, columnar alignment in vitro. In developing this alignment in vitro, this research will contribute to the overall study of growing growth for the development of improved therapeutic treatments and engineered tissues for transplants.

Equilibrium Testing Of Rat Tail Tendon: An Analysis Of The Viscoelastic Properties Of Collagen Under Different Strain Points, Joshua C. Witt

Graduate Theses - Biology & Biomedical Engineering

Instantaneous tensile testing and stress-relaxation testing are forms of mechanical testing used to determine the elastic and viscoelastic properties of biological tissue. Equilibrium testing is a form of testing that combines both of these testing approaches at different strain points to determine the elastic properties of a material and also assess their viscoelastic properties in the same test. This testing method is commonly used on highly viscoelastic materials such as cartilage but has never been fully described in dense collagenous materials such as tendon or ligament. This analysis utilizes different strain points selected to capture the classic non-linear behavior of …

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 …

Influence Of Nb On The Β → Α″ Martensitic Phase Transformation And Properties Of The Newly Designed Ti-Fe-Nb Alloys, Shima Ehtemam-Haghighi, Yujing Liu, Guanghui Cao, Lai-Chang Zhang

Research outputs 2014 to 2021

A series of Ti-7Fe-xNb (x = 0, 1, 4, 6, 9, 11 wt.%) alloys was designed and cast to investigate the β → α″ martensitic phase transformation, β phase stability, the resulting microstructure and mechanical properties. Phase analysis revealed that only Ti-7Fe-11Nb alloy shows a single body-centred cubic β phase microstructure while the others are comprised of β and orthorhombic α″ phases. Moreover, Nb addition up to 11 wt.% enhances the stability and volume fraction of β phase in the microstructure, hence reducing the propensity of the alloy system to form α″ phase during quenching. Compressive yield strength and hardness …

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 …

Enhancing Osseointegration Of Orthopaedic Implants With Titania Nanotube Surfaces, Erin A. Baker

Dissertations, Master's Theses and Master's Reports

Introduction: As joint arthroplasty surgical procedures increase annually, the development of new strategies, including novel materials and surface modifications, to attain solid bone-implant fixation are needed to increase implant terms of service. In this study, we evaluate two morphologies of titania nanotubes in both in vitro and in vivo experiments to quantify osseointegrative potential and material-level biocompatibility.

Materials and Methods: Samples were prepared via an electrochemical etching process. Two different titania nanotube (TiNT) morphologies were produced, Aligned and Trabecular. For the in vitro experiment, Sprague Dawley (SD) rat marrow-derived bone marrow cells (BMC) were seeded on samples. Alkaline phosphatase (ALP) …

Effects Of Antidepressants On Human Mesenchymal Stem Cell Differentiation On Clinically Relevant Titanium Surfaces, Nancy B. Ayad

Theses and Dissertations

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most frequently prescribed class of drugs worldwide and are implemented in the treatment of depression and other psychiatric disorders. SSRIs relieve depressive symptoms by modulating levels of the neurotransmitter serotonin in the brain. SSRIs block the function of the serotonin transporter, thereby increasing concentrations of extracellular serotonin. However, serotonin levels in the neurons of the brain only account for 5% while the remaining 95% is present outside the brain. Serotonin receptors and transporter are located on bone resident cells (mesenchymal stem cells (MSCs)), osteoblasts and osteoclasts, and serotonergic activity is believed to affect …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr

Theses and Dissertations

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …

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) …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

A Scalable Low-Cost Cgmp Process For Clinical Grade Production Of The Hiv Inhibitor 5p12-Rantes In Pichia Pastoris, Fabrice Cerini, Hubert Gaertner, Knut Madden, Ilya Tolstorukov, Scott Brown, Bram Laukens, Nico Callewaert, Jay C. Harner, Anna M. Oommen, John T. Harms, Anthony R. Sump, Robert C. Sealock, Dustin J. Peterson, Scott K. Johnson, Stephan B. Abramson, Michael M. Meagher, Robin Offord, Oliver Hartley

Department of Chemical and Biomolecular Engineering: Faculty Publications

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

A Collagen Based Tissue Engineered Heart Valve Shows Excellent Functionality And Remodelling After Dynamic Conditioning, Claire Brougham, Ricardo Moreira, Tanya J. Levingstone, Stefan Jockenhoevel, Petra Mela, Fergal J. O'Brien

Conference Papers

No abstract provided.

Incorporation Of Fibrin Into A Collagen–Glycosaminoglycan Matrix Results In A Scaffold With Improved Mechanical Properties And Enhanced Capacity To Resist Cell-Mediated Contraction, Claire Brougham, Tanya J. Levingstone, Stefan Jockenhoevel, Thomas C. Flanagan, Fergal J. O'Brien

Articles

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with …

Mechanical Characterization Of Carbon Fiber And Thermoplastic Ankle Foot Orthoses, Amanda Wach

Master's Theses (2009 -)

The needs of an increasingly young and active orthotic patient population has led to advancements in ankle foot orthosis (AFO) design and materials to enable higher function. The Intrepid Dynamic Exoskeletal Orthosis (IDEO) is a custom energy-storing carbon fiber AFO that has demonstrated improved clinical function, allowing patients to return to high-intensity activities such as sports and military service. An improved understanding of AFO mechanical function will aid prescription and fitting, as well as assist in design modifications for different patient populations. This study investigated the mechanical properties of AFOs, specifically structural stiffness, rotational motion, and strut deflection, to discern …

The Role Of Biological Fluid And Dynamic Flow In The Behavior And Cellular Interactions Of Gold Nanoparticles, Emily K. Breitner, Saber M. Hussain, Kristen K. Comfort

Chemical and Materials Engineering Faculty Publications

Background: Due to their distinctive physicochemical properties, nanoparticles (NPs) have proven to be extremely advantageous for product and application development, but are also capable of inducing detrimental outcomes in biological systems. Standard in vitro methodologies are currently the primary means for evaluating NP safety, as vast quantities of particles exist that require appraisal. However, cell-based models are plagued by the fact that they are not representative of complex physiological systems. The need for a more accurate exposure model is highlighted by the fact that NP behavior and subsequent bioresponses are highly dependent upon their surroundings. Therefore, standard in vitro models …

Bioengineered Cell Niche For Skeletal Muscle Regeneration, Nicole M. Whittern, Naagarajan Narayanan, Chunhui Jiang, Owen Jones, Jay Gilbert, Michael Whittern, Shihuan Kuang, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Skeletal muscles can self-repair minor strains, lacerations, and contusions; however, in cases of volumetric muscle lossand muscle degenerative diseases, tissue fails to regenerate. Current cell-based therapies, such as myoblast transplantation, have significant drawbacks of low survival rates and engraftment efficacy, mainly due to the absence of supportive cell microenvironment. Scaffolds that mimic the natural cell microenvironment provide a robust platform to support cell adhesion, migration, proliferation, and differentiation. Electrospinning is a versatile technology platform used for fabricating the fiber scaffold that mimics the extracellular matrix. Thus, we aim to reconstitute the cell microenvironment through development of aligned fiber scaffolds by …

Adsorption Mechanisms Of Palladium On The Tobacco Mosaic Virus Surface, Gloriia D. Novikova, Oluwamayowa Adigun, Erin Retzlaff-Roberts, Michael T. Harris

The Summer Undergraduate Research Fellowship (SURF) Symposium

Organic-inorganic materials synthesis using biological templates has recently drawn immense attention of researchers. Biotemplating has shown to be an efficient and economic means of nanomaterials production. Naturally stable, readily available and genetically malleable, Tobacco Mosaic Virus (TMV) is one of the most extensively studied and characterized biotemplates. Particularly, templated synthesis using TMV has produced high quality nanorods and nanowires that have been applied to batteries, memory devices and catalysis. The fundamental mechanisms, governing the adsorption of palladium on the TMV Wild Type and genetically modified versions (TMV1Cys and TMV2Cys), are not fully understood; this knowledge, however, is essential for future …

Ultrasound-Guided Nanobubbles For Targeted Drug Delivery, Pei Yang, Pushpak Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

In a large number of biological and environmental applications, ultrasound (US)-powered micro- and nano-motors have attracted considerable attention. However, their applications in biological settings have been limited due to the incompatibility of metallic motors and the lack of precision guiding. Here, we demonstrate that cellulosic polymer nanobubbles (200-800nm) can be propelled, aligned, accelerated, and assembled in solution using Doppler ultrasound beam (DUB) and simultaneously imaged using low-frequency ultrasound. Results show that by utilizing Doppler ultrasound beam (DUB), nanobubbles accumulation at a pre-determined site can be enhanced. Moreover, bubbles’ trajectory and velocity can be also be manipulated. Related parameters associated with …

Buckling-Driven Force Generation Of Cell Cortex, Pranith Lomada, Wonyeong Jung, Taeyoon Kim

The Summer Undergraduate Research Fellowship (SURF) Symposium

Actomyosin cortex, a thin network underlying cell membrane, is known to generate a large portion of tensile forces required for various cellular processes. Recently, theoretical studies predicted that buckling of actin filaments breaks symmetry between tensile and compressive forces developed by myosin motors, resulting in tensile stress at a network level. However, the significance of the filament buckling of the cortex has yet to be demonstrated either computationally or experimentally. Here, buckling-dependent stress generation of the cortex-like actomyosin network was investigated using an agent-based computational model consisting of actin filaments, actin cross-linking proteins (ACPs), and molecular motors. First, a wide …

Harnessing Notch Signaling For Biomaterial Scaffold-Based Bone Regeneration, Helena P. Lysandrou, Chunhui Jiang, Naagarajan Narayanan, Shihuan Kuang, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Bone fracture has recently become prevalent, especially with an increasingly aging population. Current bone grafts procedures, including autografts and allografts, are hindered by multiple factors, such as limited supplies and inconsistent bone healing. Scaffold-based bone tissue engineering emerges as a prospective strategy to aid in bone regeneration through delivery of growth factors such as bone morphogenic proteins (BMPs). However, the use of BMPs suffers from several drawbacks such as protein instability and immunogenicity. Therefore, there exists a great need for the development of novel therapies to promote bone healing. Notch signaling, a pathway critical for cell-fate determination has been shown …

Breast Cancer/Stromal Cells Coculture On Polyelectrolyte Films Emulates Tumor Stages And Mirna Profiles Of Clinical Samples, Amita Daverey, Karleen M. Brown, Srivatsan Kidambi

Department of Chemical and Biomolecular Engineering: Faculty Publications

In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell−cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes …

Molecular Dynamics Investigation Of The Arabinan-Cellulose Interface For Cellulose Nanocomposite Applications, Luke Thornley

Materials Engineering

Atom level computer simulations of the arabinan and cellulose interface were performed to better understand the mechanisms that give arabinan-cellulose composites (ArCCs) their strength with the goal to improve man-made ArCCs. The molecular dynamics (MD) software LAMMPS was used in conjunction with the ReaxFF/c force field to model the bond between cellulose and arabinan. A cellulose nanocrystal with dimensions 51 x 32 x 8 Å was minimized with various weight percent of water, 0%, 3%, 5%, 8%, 10%, and 12%. After the system was equilibrated for at least 100,000 femtoseconds, an arabinan molecule composed of 8 arabinose rings was added …