Other Biomedical Engineering and Bioengineering Commons^™

Optimization Of A Novel Barnes Maze Protocol For Assessing Antioxidant Treatment Of Traumatic Brain Injury, Connor C. Gee

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Current preclinical research into traumatic brain injury focuses heavily upon cellular and molecular testing to determine the effects of injury and potential benefits of neuroprotective treatments. While this may be a useful method, some argue that an increased focus on behavioral testing could lead to better clinical translation as these assays assess the longer term, downstream effects from a brain injury. The most characterized behavioral tests used in traumatic brain injury research are the spatial learning and memory paradigms, Morris Water Maze and Barnes Maze. The Morris Water Maze is the most used of theses paradigms and relies on spatial …

Preclinical Development Of Single Walled Carbon Nanotube-Based Optical Biosensors, Eric M. Hofferber

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

High resolution, long-term monitoring of key biological analytes would improve patient outcomes by providing earlier detection of disease states and improved efficacy of treatment. One class of biosensors that have gained much attention in recent years are optical biosensors. Optical probes are attractive biosensors due to their noninvasive nature of detection, as certain light can pass through tissue, water, and blood. Single walled carbon nanotubes (SWNT) are a specific type of optical biosensor that fluoresce in the near infrared range of the electromagnetic spectrum and offer unparalleled spatial and temporal resolution. SWNT have been applied as biosensors in vitro, …

Synthetic Lethality In Pediatric Brain Cancer Cells By Optimized Plga Nanoparticles And Drug Combinations, Megan Ruckman, Megan Otte, Forrest Kievit

UCARE: Research Products

Here we test drugs effectiveness to inhibit various DNA repair pathways with the purpose of sensitizing cancer cells to radiotherapy. We work on optimizing delivery of DNA repair pathway inhibiting drugs by the use of PLGA nanoparticles.

Fibrinogen, Factor Xiii And Fibronectin: A Biophysical And Kinetic Characterization Of Their Interactions, Frank Fabian

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

The development of recombinant-based liquid fibrin tissue sealants having enhanced hemostatic and wound healing properties will involve understanding as yet not well characterized interactions between fibrinogen, fibrin (Fbn) factor XIII, thrombin and fibronectin. We study these phenomena in the context of comparing plasma derived fibrinogen to recombinant fibrinogen (rFI) produced in the milk of transgenic cows. An abundance of purified γγ and γγ’ FI subspecies enables detailed study of γγ or γγ’ biomonomer and their respective Fbn biopolymer formation as having different substrate behaviors of activated plasma derived factor XIII (pFXIIIa₂b₂). High pressure size exclusion (HPSEC) …

Using Synthetic Lethality To Sensitize Pediatric Brain Cancer Cells To The Dna Damaging Effects Of Radiation Therapy, Megan Ruckman, Rose Nelson, Forrest Kievit

UCARE: Research Products

Brain tumors are the leading cause of cancer related deaths in children. As a treatment, radiotherapy is very effective, but it also comes with many severe side effects, such as radiation-induced adverse developmental and psychosocial effects.² Cancer, because it is a mutagenic disease, is by definition a disease of DNA repair pathways. Here we utilize drugs to inhibit various DNA repair pathways with the purpose of sensitizing cancer cells to radiotherapy so that lower doses may be used. Hopefully this would improve the lifelong outcomes of patients that would otherwise not survive or would be left with lifelong neurocognitive …

Preparation And Characterization Of Functionalized Heparin-Loaded Poly-Ɛ-Caprolactone Fibrous Mats To Prevent Infection With Human Papillomaviruses, Daniela Gonzalez, Jorge Ragusa, Peter C. Angeletti, Gustavo F. Larsen

Department of Chemical and Biomolecular Engineering: Faculty Publications

In this study, heparin-loaded poly-ε-caprolactone (PCL) fibrous mats were prepared and characterized based on their physical, cytotoxic, thermal, and biological properties. The main objective of the work described here was to test the hypothesis that incorporation of heparin into a PCL carrier could serve as bio-compatible material capable of inhibiting Human Papillomavirus (HPV) infection. The idea of firmly anchoring heparin to capture soluble virus, vs. a slow heparin release to inhibit a virus in solution was tested. Thus, one material was produced via conventional heparin matrix encapsulation and electrohydrodynamic fiber processing in one step. A second type of material was …

Eigenstrain As A Mechanical Set-Point Of Cells, Shengmao Lin, Marsha C. Lampi, Cynthia A. Reinhart-King, Gary C.P. Tsui, Jian Wang, Carl A. Nelson, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Cell contraction regulates how cells sense their mechanical environment. We sought to identify the set-point of cell contraction, also referred to as tensional homeostasis. In this work, bovine aortic endothelial cells (BAECs), cultured on substrates with different stiffness, were characterized using traction force microscopy (TFM). Numerical models were developed to provide insights into the mechanics of cell–substrate interactions. Cell contraction was modeled as eigenstrain which could induce isometric cell contraction without external forces. The predicted traction stresses matched well with TFM measurements. Furthermore, our numerical model provided cell stress and displacement maps for inspecting the fundamental regulating mechanism of cell …

A Tunable, Three-Dimensional In Vitro Culture Model Of Growth Plate Cartilage Using Alginate Hydrogel Scaffolds, Alek G. Erickson, Taylor D. Laughlin, Sarah Romereim, Catherine Sargus-Patino, Angela K. Pannier, Andrew T. Dudley

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector. In this cartilage, growth is generated via a differentiation program that is spatially and …

Design And Validation Of An In Vivo Long-Term Attachment Capsule Robot, Wanchuan Xie

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

The invention of capsule endoscopy (CE) made the non-invasive monitoring of the entire small bowel possible and became the primary means for diagnosing small bowel pathology. In the last decade, capsule robots have been transformed from diagnostic devices into a widely studied biomedical platform with the potential for active locomotion, drug delivery and therapeutic capabilities. To perform accurate on-site drug release and therapy, it is necessary for a capsule robot to be able to attach to the intestinal tissue and maintain its position long-term. Design challenges derive from the task of long-term mucosal adhesion which requires firm, quick-response attachment without …

A Novel Biochamberfor Modeling Of Atherosclerotic Arteries: In Vitro Capabilities And Applications, Iman Salafian, Angelos Karagiannis, Benjamin S. Terry, Yiannis S. Chatzizisis

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Atherosclerosis is a chronic disease that involves the lipid accumulation and inflammation of the arterial wall [1,2]. Despite great efforts,its pathophysiology has not been fully elucidated. Existent drugs can reduce its progression but there are no available drugs to prevent its complications [3,4]. Atherosclerosis remains the leading global cause of death[5].

The purpose of this work is to design and build a customized biochamber which can be used for the following studies:

•Study the pathophysiology of atherosclerosis in vitro & ex vivo

•Investigate the mechanisms of atherosclerotic plaque disruption

•Examine the direct effect of different anti-atherosclerotic drugs on lesions

•Use …

Chemical And Physical Priming Of Human Mesenchymal Stem Cells To Alter Nonviral Gene Delivery Outcomes, Tyler Kozisek, Andrew Hamann, Amy Mantz, Mathias Schubert, Eva Schubert, Angela K. Pannier

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Human Mesenchymal Stem Cells: Human mesenchymal stem cells (hMSCs) are a multipotent cell, meaning they are able to differentiate into a more mature cell type, such as osteocytes, chondrocytes, and adipocytes, that are found in numerous tissues in the human body, such as bone marrow, fat, and muscle. Since hMSCs can be derived from adult human tissues, they do not have the same ethical concern associated with them as other stem cells, such as embryonic stem cells. Due to hMSCs multipotency and ease of obtaining, they have become one of the most widely researched stem cell types in areas such …

A Comprehensive Dosimetric Study On Switching From A Type-B To A Type-C Dose Algorithm For Modern Lung Sbrt, Christina Zhou, Nathan Bennion, Rongtao Ma, Xiaoying Liang, Shuo Wang, Kristina Zvolanek, Megan Hyun, Xiaobo Li, Sumin Zhou, Weining Zhen, Chi Lin, Andrew Wahl, Dandan Zheng

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Background: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning.

Methods: Fifty-two lung SBRT patients were included, each …

A Method For Measuring The Attachment Strength Of The Cestode Hymenolepis Diminuta To The Rat Intestine, Wanchuan Xie, Gábor R. Rácz, Benjamin S. Terry, Scott Lyell Gardner

Scott L. Gardner Publications

A unique adaptation of many internal parasites of mammals is their ability to stay in the intestine for extended periods of time and resist the normal peristaltic movements and forces that push and expel material. To better understand parasite adhesion behavior and replicate their attachment method in medical devices, an experiment was designed and performed using the rat tapeworm, Hymenolepis diminuta. The experiment employed a tensile test machine and a digital scale and was designed to calculate the attachment strength of the scolex to the mucosa through the change of the value of the digital scale during the tensile …

Characterization Of Molecular Communication Based On Cell Metabolism Through Mutual Information And Flux Balance Analysis, Zahmeeth Sayed Sakkaff

School of Computing: Dissertations, Theses, and Student Research

Synthetic biology is providing novel tools to engineer cells and access the basis of their molecular information processing, including their communication channels based on chemical reactions and molecule exchange. Molecular communication is a discipline in communication engineering that studies these types of communications and ways to exploit them for novel purposes, such as the development of ubiquitous and heterogeneous communication networks to interconnect biological cells with nano and biotechnology-enabled devices, i.e., the Internet of Bio-Nano Things. One major problem in realizing these goals stands in the development of reliable techniques to control the engineered cells and their behavior from the …

Hyaluronic Acid-Conjugated Liposome Nanoparticles For Targeted Delivery To Cd44 Overexpressing Glioblastoma Cells, Stephen L. Hayward, Christina L. Wilson, Srivatsan Kidambi

Department of Chemical and Biomolecular Engineering: Faculty Publications

Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study …

Analysis Of Breath-Holding Index As An Assessment Of Cerebrovascular Reactivity, Allison P. Porter, Madison Burger, Mohammed Alwatban, Benjamin Hage, Greg Bashford

UCARE: Research Products

Cerebrovascular reactivity (CVR) is a key factor in regulating blood flow into the brain, and a marker for vascular disease. If the brain's regulatory system is not working, a patient may be in serious trouble. Testing of CVR is one method of assessing the brain's regulatory capabilities. Transcranial Doppler ultrasound (TCD) is one tool to measure CVR. In this method, carbon dioxide in the blood is transiently increased (such as with the holding of breath), and the resulting blood flow in the brain is measured. In this study, we are going to measure the variability of the breathholding index.

Within …

Circle Of Willis Model For Transcranial Doppler Ultrasound Training, Conner J. Beyersdorf, Ben Hage, Greg Bashford

UCARE: Research Products

Transcranial Doppler (TCD) ultrasound is a technique involving the use of high frequency transmitters to measure intracranial blood flow. The brain is supplied by blood in an arterial anastomosis called the Circle of Willis. Using TCD ultrasound on the circle is difficult and requires practice and teaching. A functional model of the Circle of Willis could prove to be a valuable teaching tool. Through the use of AutoCAD and 3D printing software, an anatomically accurate model was created and set in gelatin phantom inside of a plastic skull. Milk was pumped through the model with a peristaltic pump to simulate …

Computational Characterization Of Exogenous Micrornas That Can Be Transferred Into Human Circulation, Jiang Shu, Kevin Chiang, Janos Zempleni, Juan Cui

School of Computing: Faculty Publications

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of …

Biomechanical Investigation Of Elite Place-Kicking, Chase M. Pfeifer

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Many studies aim to understand the fundamentals of kicking commonly displayed by soccer players [4,6,10,16,17,18,24,25,28,29,30,34,36,38,40]. Of those studies, most are limited to a two-dimensional (2D) analysis using high-speed cameras for position tracking or utilizing electromyography to observe the activity of select muscles [4,6,18,25,29,36]. The few studies that investigate kicking using a three-dimensional (3D) model are limited in their position tracking capabilities and focus mainly on joint flexion potentials and foot speed.

This dissertation is a comprehensive biomechanical analysis (kinematic and EMG) of the field-goal place-kicking techniques of four elite kickers in American football. Data were compared and contrasted with ball …

Modeling The Contributions Of Hand Loads To Cervical Spine Compressive Forces, Mohamed R.S. Amar

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

The purpose for this study is threefold. All involve single handed lifting tasks where the height of the lifted object, the distance of the lifted object from the body, and the angle of the lift relative to the body were varied. First, examine the activity of each of the shared musculature of selected shared muscles between the shoulder and cervical spine. Second, attempt to empirically model the activations of the shared muscles. Third, to understand the relationship between the active and antagonistic contraction. Finally, to establish a biomechanical model to estimate the compressive forces on the cervical spine.

Ten subjects …

Blast-Induced Mild Traumatic Brain Injury Through Ear Canal: A Finite Element Study, Praveen Akula, Yi Hua, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose The role of ear canal in transmitting blast waves to the brain is not clear. The goal of this work is to characterize the influence of ear canal on blast-induced mild traumatic brain injury through a computational approach.

Methods A three-dimensional human head model with single-side ear canal details was reconstructed from computed tomography images. The ear canal was positioned either facing the incident blast wave or facing away from the blast wave.

Results The blast wave-head interaction has demonstrated that the overpressure within the ear canal was substantially amplified when the ear directly faced the blast wave. When …

Characterization Of Closed Head Impact Injury In Rat, Yi Hua, Praveen Akula, Matthew Kelso, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

The closed head impact (CHI) rat models are commonly used for studying the traumatic brain injury. The impact parameters vary considerably among different laboratories, making the comparison of research findings difficult. In this work, numerical CHI experiments were conducted to investigate the sensitivities of intracranial responses to various impact parameters (e.g., impact depth, velocity, and position; impactor diameter, material, and shape). A three-dimensional finite element rat head model with anatomical details was subjected to impact loadings. Results revealed that impact depth and impactor shape were the two leading factors affecting intracranial responses.The influence of impactor diameter was region-specific and an …

A Highly Adaptive And Cost Effective Second Generation Incubator (Sgi) Towards Educational, Research And Clinical Processes, Yassir H. Al-Sayagh

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Today´s rising demand for more reliable and affordable alternatives to organ transplant has led to a growing market for in vitro tissue culture systems. The main objective of tissue engineering as a whole is to employ human tissue equivalents for commercial use. The state-of-the-art processes for producing these so called tissue models are still very expensive, difficult to produce and time-consuming.

To engineer tissues, in vitro, a three-dimensional support structure commonly termed scaffold is needed. Stem cells are then added to the scaffold. In order for tissue to materialize, the scaffold and the cells must be incubated (cultured) at a …

Experimental And Numerical Investigation Of The Mechanism Of Blast Wave Transmission Through A Surrogate Head, Yi Hua, Praveen Akula, Linxia Gu, Jeff Berg, Carl A. Nelson

Department of Mechanical and Materials Engineering: Faculty Publications

This work is to develop an experiment-validated numerical model to elucidate the wave transmission mechanisms through a surrogate head under blast loading. Repeated shock tube tests were conducted on a surrogate head, i.e., water-filled polycarbonate shell. Surface strain on the skull simulant and pressure inside the brain simulant were recorded at multiple locations. A numerical model was developed to capture the shock wave propagation within the shock tube and the fluid-structure interaction between the shock wave and the surrogate head. The obtained numerical results were compared with the experimental measurements. The experiment-validated numerical model was then used to further understand …

Developing Defined And Scalable 3d Culture Systems For Culturing Human Pluripotent Stem Cells At High Densities, Yuguo Lei, Daeun Jeong, Jifang Xiao, David V. Schaffer

Department of Chemical and Biomolecular Engineering: Faculty Publications

Human pluripotent stem cells (hPSCs)—including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)—are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation. Here, we describe additional design rationale and characterization of this …

Application Of Limited Mixing In The Hele–Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Evaluation Of Endogenous Allergens For The Safety Evaluation Of Genetically Engineered Food Crops: Review Of Potential Risks, Test Methods, Examples And Relevance, Richard E. Goodman, Rakhi Panda, Harsha Ariyarathna

Department of Food Science and Technology: Faculty Publications

The safety of food produced from genetically engineered (GE) crops is assessed for potential risks of food allergy on the basis of an international consensus guideline outlined by the Codex Alimentarius Commission (2003). The assessment focuses on evaluation of the potential allergenicity of the newly expressed protein(s) as the primary potential risk using a process that markedly limits risks to allergic consumers. However, Codex also recommended evaluating a second concern, potential increases in endogenous allergens of commonly allergenic food crops that might occur due to insertion of the gene. Unfortunately, potential risks and natural variation of endogenous allergens in non-GE …

Application Of Response Surface Methodology And Central Composite Design For 5p12-Rantes Expression In The Pichia Pastoris System, Frank M. Fabian

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

Pichia pastoris has demonstrated the ability to express high levels of recombinant heterologous proteins. Protein expression is enhanced during fermentation at high cell density. However, the level of expression is mainly regulated by fermentation operation factors. This research is directed to investigate the effect of methanol growth rate, temperature and pH in the expression of the total 5P12-Rantes concentration, expression of active 5P12-Rantes and Specific yield using the response surface methodology and central composite design.

The response surface methodology, RSM, has been used successfully used by Zhang, W. and Ian, M. to optimize the cell density and fermentation process. The …

Morphometric, Biochemical, And Raman Spctral Analyses Of Muscle Damage In Patients With Peripheral Arterial Disease: Provising Objective Criteria For Diagnosis And Treatment Monitoring, Kim Cluff

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Peripheral arterial disease (PAD), which affects approximately 10 million Americans, is characterized by atherosclerosis of the non-coronary arteries. PAD produces a progressive accumulation of ischemic injury to the limbs that is reflected in a gradual worsening in the myofiber morphology and oxidative damage in the gastrocnemius muscle. In this study, we evaluated the hypothesis that quantitative morphological and biochemical parameters of gastrocnemius myofibers change in a consistent manner during the progression of PAD, provide an objective grading of muscle degeneration in the ischemic limb, and correlate to clinical stage of PAD. Myofiber morphometrics were determined precisely with mathematical equations that …

The Influence Of Heterogeneous Meninges On The Brain Mechanics Under Primary Blast Loading, Linxia Gu, Mehdi S. Chafi, Shailesh Ganpule, Namas Chandra

Department of Mechanical and Materials Engineering: Faculty Publications

In the modeling of brain mechanics subjected to primary blast waves, there is currently no consensus on how many biological components to be used in the brain–meninges–skull complex, and what type of constitutive models to be adopted. The objective of this study is to determine the role of layered meninges in damping the dynamic response of the brain under primary blast loadings. A composite structures composed of eight solid relevant layers (including the pia, cerebrospinal fluid (CSF), dura maters) with different mechanical properties are constructed to mimic the heterogeneous human head. A hyper-viscoelastic material model is developed to better represent …