Biomedical Engineering and Bioengineering Commons^™

Long-Term Velaglucerase Alfa Treatment In Children With Gaucher Disease Type 1 Naïve To Enzyme Replacement Therapy Or Previously Treated With Imiglucerase, Laurie Smith, William Rhead, Joel Charrow, Suma P. Shankar, Ashish Bavdekar, Nicola Longo, Rebecca Mardach, Paul Harmatz, Thomas N. Hangartner, Hak-Myung Lee, Eric Crombez, Gregory M. Pastores

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Background

Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427).

Methods

Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30–60 U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty.

Results

The study included 24 …

Introduction To Biomedical Engineering, Maribel Vazquez

Open Educational Resources

An overview of the field of biomedical engineering designed to acquaint the students with its interdisciplinary nature; research areas presented by the biomedical engineering faculty.

Supervised Learning-Based Explicit Nonlinear Model Predictive Control And Unknown Input Estimation In Biomedical Systems, Ankush Chakrabarty

Open Access Dissertations

Application of nonlinear control theory to biomedical systems involves tackling some unique and challenging problems. The mathematical models that describe biomedical systems are typically large and nonlinear. In addition, biological systems exhibit dynamics which are not reflected in the model (so-called 'un-modeled dynamics') and hard constraints on the states and control actions, which exacerbate the difficulties in designing model-based controllers or observers.

This thesis investigates the design of scalable fast explicit nonlinear model predictive controllers (ENMPCs). The design involves (i) the estimation of a feasible region using Lyapunov stability methods and support vector machines; and (ii) within the estimated feasible …

Effects Of Intraframe Distortion On Measures Of Cone Mosaic Geometry From Adaptive Optics Scanning Light Ophthalmoscopy, Robert F. Cooper, Yusufu N. Sulai, Adam M. Dubis, Toco Y.P. Chui, Richard B. Rosen, Michel Michaelides, Alfredo Dubra, Joseph Carroll

Biomedical Engineering Faculty Research and Publications

Purpose: To characterize the effects of intraframe distortion due to involuntary eye motion on measures of cone mosaic geometry derived from adaptive optics scanning light ophthalmoscope (AOSLO) images.

Methods: We acquired AOSLO image sequences from 20 subjects at 1.0, 2.0, and 5.08 temporal from fixation. An expert grader manually selected 10 minimally distorted reference frames from each 150-frame sequence for subsequent registration. Cone mosaic geometry was measured in all registered images (n ¼ 600) using multiple metrics, and the repeatability of these metrics was used to assess the impact of the distortions from each reference frame. In nine additional subjects, …

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 …

Effect Of Temporal Onset Of Mechanical Loading On Tendon To Bone Healing, Determined With A Novel In-Vivo Device, Mark E. Stasiak

Dissertations, Theses, and Capstone Projects

Background: Exposure to tensile loading has been shown to maintain tendon/ligament homeostasis, with the tensile modulus of the tissue increasing in response to greater loading frequency, and even decreasing in the absence of load. However after injury or surgical repair the effect of tensile load is controversial, with many studies implicating mechanical loading with impaired healing. It is currently unknown when the tensile loading imparted during rehabilitation exercise, can be safely reintroduced after surgical tendon repair or ligament reconstruction, and at what time point it can most benefit the remodeling process. To investigate the effect of tensile loading protocols on …

Investigating Neural Mechanisms Of Hand Movements In Virtual Reality, Chuang Mu

Theses

Mirror visual feedback (MVF), a technique by which movement of one limb is perceived as movement of the contralateral limb, has the capacity to relieve phantom limb pain or promote motor recovery of the upper limbs after stroke (Ramachandran et al., 1995). Functional MRI studies have demonstrated activation of the motor areas in the hemisphere ipsilateral to the moving hand in response to MVF. However, the neural mechanisms of MVF are still unclear. This Electroencephalography (EEG) study was designed to investigate the timing of neural responses to MVF presented in virtual reality. 16 right-handed, neurologically healthy subjects participated in a …

A Study Of Kinematics And Kinetics In Time-Constrained Arm Movements, Oyindamola Owoeye

Theses

Several studies such as the equilibrium point hypothesis (EPH) purport that the motor signals that descend from the brain instead of encoding muscle torques, influence an existing relationship between muscle torque and body configuration.

In the present study, the possibility of torque depending explicitly on position was tested using a task in which subjects (N=5) moved a simulated weightless frictionless mass through a small (<8 degree) elbow extension in order to move a cursor on a screen to a target location. Each subject completed 720 trials. On ~10% of trials the simulated mass was increased unknown to the subject. The relationship between the cursor’s position and the torque applied to the system was held constant even when the simulated mass was increased. Thus, any change in torque produced was neither due the subjects’ perception of the mass nor due to their perception of the cursor. The time at which the subjects torque changed direction was seen to be significantly different (p<0.005) during trials which the mass changed. This change in torque is concluded to be position-dependent. However the possibility of this being a merely mechanical effect could not be ruled out by due to poor EMG collection.

A post-hoc analysis of different position-dependent motor control models, was done. Particularly, an exponential spring model, a linear spring model, and a linear spring with relative damping model were each tested to see how well …

Realization Of Dynamixel Servo Plant Parameters To Improve Admittance Control For A Compliant Human-Robot Interaction, Ahmad Zahid Rao

Theses

In theory, admittance control offers a very effective method of implementing smooth human-robot interaction. It allows the user’s applied force to control the movement of a powerful robot as if the robot were a small, passive mass. However, the real-world application of admittance control faces limitation posed by the dynamics of servo motors, the accuracy of the force sensors, and the computation speed of processors.

This research investigates the limitations on achieving compliant passive behavior when using state-of-the-art actuators, sensors and processors. The work involves characterizing the dynamic behavior of the servo motors, development of improved differential equations representing admittance …

Comparison Of Muscle Synergies Elicited From Transcranial Meganetic Stimulation (Tms) And Voluntary Movements, Yifei Wei

Theses

A key question in motor control is the redundancy of musculoskeletal elements involved. This problem refers to as the degree of freedom problem. The Muscle Synergy Hypothesis is one of the hypotheses that aim to resolve the problem which defines that a muscle synergy is a combination of a small set of muscles activated at different levels, serving as a building block that constructs motor behaviors. A recent study (Overduin et al. 2012) demonstrated that muscle synergies decomposed by Nonnegative Matrix Factorization (NMF) from EMG patterns evoked by intra-cortical microsimulation (ICMS) in the monkey remarkably matched ones observed in naturalistic …

Rodent Testing Device Surrogate For Shockwave Blast Testing, Anthony C. Misistia

Theses

Many laboratories around the world are conduct shockwave blast injury tests on rodents to simulate blast traumatic brain injury (TBI). Each of these laboratories has different techniques for creating the shockwave blasts as well as positioning the rats. There is no device to determine whether or not the rodent animal models actually experiences a true blast wave in a given set up. This device was developed as a method for verifying rodents undergoing true shockwave blasts through biometrics, instrumentation and the basic biomechanical responses a rodent experiences during such tests. Since the goal of shockwave blast testing is to replicate …

Plasticity Of The Cortical Representation Of Finger Extensors Induced By Paired Associative Stimulation, Ian Anthony Gerard Lafond

Dissertations

This dissertation first explored associative plasticity of the human motor cortical representation with the use of noninvasive transcranial magnetic stimulation (TMS) paired with peripheral electrical stimulation. Paired Associative Stimulation (PAS) has grown in popularity because of its potential clinical applications. PAS techniques are used in combination with electromyography (EMG) measurements to study cortical excitability and features of hand movement. This work focuses on a cohesive approach to answer central questions about: the ideal mechanism to facilitate cortical plasticity via PAS, the interaction between the behavior performed and type of stimulation delivered to the targeted cortical network and the effects of …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Bioenergy From Wastewater-Based Biomass, Ronald C. Sims, Sean K. Bedingfield, Reese Thompson, Judith L. Sims

Biological Engineering Faculty Publications

The U.S. Department of Energy (DOE) has stated that biomass is the only renewable resource that can supplant petroleum-based liquid transportation fuels in the near term. Wastewater is beginning to be viewed as a potential resource that can be exploited for biomass production and conversion to bioenergy. We suggest that using wastewater from municipalities and industries as a resource for cultivating biomass and combining wastewater treatment with the production of biomass for bioenergy would provide benefits to both industries. Two waste-based biomass production systems that currently have large nationwide infrastructures include: (1) wastewater treatment systems that can be used to …

Development Of A Glucose-Powered Biobattery For Implantation And Use In Humans, Carson Sparks, Cody Maughan, Lucas Smith, Carson Sparks

Research on Capitol Hill

With current demands for implantable electrical devices increasing, the need for a more stable and biocompatible source of power is becoming increasingly necessary. Several battery types and materials were evaluated. Ultimately, an abiotic biobattery was designed with the goal of implantation in the human body. Nafion, single-walled carbon nanotubes (SWCNTs), and gold were used to create an abiotic biobattery that is powered by glucose.

The SWCNTs were used to create the cathode, the gold was used to fabricate the anode, and the Nafion acted as the separator between the cathode and anode. A thin Nafion membrane was evaluated for overlaying …

Improved Production Of Promising Antioxidant, Resveratrol, In Escherichia Coli, Chad Skidmore

Research on Capitol Hill

Resveratrol is a promising antioxidant natural product. Studies have shown that it is effective against heart disease, cancer, Alzheimer's disease, diabetes, and harmful UV rays. This health-benefiting molecule is present in plants such as peanuts, berries, and the skin of red grapes.

A growth time of 10 months makes Japanese knotweed an impractical source of resveratrol. A more efficient way to produce resveratrol has been found by using E. coli as tiny biological factories.

Zeta Potential: Key To Harvesting Algae For Biofuels And Bioproducts, Celeste Hancock, Michael Flores

Research on Capitol Hill

• Algae is an effective and sustainable resource for creating a broad spectrum of bioproducts.
• Scientists have found it challenging to harvest algae due to the difficulty of collecting algae when in an aqueous solution such as wastewater.
• Rotating Algal Biofilm Reactors (RABRs) coated with carbon nanotubes have proved effective. The RABR floats in an aqueous environment and attracts charged algal particles in suspension.
• The tendency for algae to favor suspension over coagulation occurs only when particles of algae are sufficiently charged. This charge can be measured by analyzing the electric potential at the interface between the surface of a particle …

Beyond The Fiber: Novel Spider Silk Coatings And Adhesives, Danielle A. Gaztambide, Breton A. Day

Research on Capitol Hill

Natural spider silks have long been recognized for their combination of incredible strength and elasticity. Spider silk is more elastic than nylon, tougher than Kevlar, and stronger than steel by weight. Due to an inability to farm spiders, much work has been done to produce spider silks in transgenic hosts for large -scale production. Our work was done using recombinant spider silk proteins produced in transgenic goats and the bacteria E. coli.

More recently spider silks have also been recognized for their biocompatibility and lack of immunogenicity. Spider silks' incredible strength and ability to be implanted safely within the body …

Wavelet Coherence Analysis Of Dynamic Cerebral Autoregulation In Neonatal Hypoxic–Ischemic Encephalopathy, Fenghua Tian, Takashi Tarumi, Hanli Liu, Rong Zhang, Lina Chalak

Bioengineering Faculty Publications - Archive

Cerebral autoregulation represents the physiological mechanisms that keep brain perfusion relatively constant in the face of changes in blood pressure and thus plays an essential role in normal brain function. This study assessed cerebral autoregulation in nine newborns with moderate-to-severe hypoxic–ischemic encephalopathy (HIE). These neonates received hypothermic therapy during the first 72 h of life while mean arterial pressure (MAP) and cerebral tissue oxygenation saturation (SctO2) were continuously recorded. Wavelet coherence analysis, which is a time-frequency domain approach, was used to characterize the dynamic relationship between spontaneous oscillations in MAP and SctO2. Wavelet-based metrics of phase, coherence and gain were …

Multimodal, Biomaterial-Focused Anticoagulation Via Superlow Fouling Zwitterionic Functional Groups Coupled With Anti-Platelet Nitric Oxide Release, Kagya Amoako, Harihara S. Sundaram, Ahmed Suhaib, Shaoyi Jiang, Keith E. Cook

Mechanical and Industrial Engineering Faculty Publications

The functions of anti-fouling, zwitterionic polycarboxybetaine (pCB) and anti-platelet nitric oxide (NO) release replicate key anticoagulant properties of the endothelium. The two approaches, only tested separately thus far, were paired on gas permeable polydimethylsiloxane (PDMS) membranes and evaluated for anti-coagulation. Uncoated PDMS (control) and PDMS coated with pCB were screened for fibrinogen (Fg) fouling followed by platelet adsorption testing to evaluate the effects of coating and/or NO using bioreactors. Bare or coated PDMS membranes separated sheep plasma (108 platelets/ml) and gas flow chambers within the bioreactors. Either 100 or 0 ppm of NO/N2 flowed through the gas chamber for NO …

Uncoupling Shear And Uniaxial Elastic Moduli Of Semiflexible Biopolymer Networks: Compression-Softening And Stretch-Stiffening., Anne S G Van Oosten, Mahsa Vahabi, Albert J Licup, Abhinav Sharma, Peter Galie, Fred C Mackintosh, Paul A Janmey

Henry M. Rowan College of Engineering Departmental Research

Gels formed by semiflexible filaments such as most biopolymers exhibit non-linear behavior in their response to shear deformation, e.g., with a pronounced strain stiffening and negative normal stress. These negative normal stresses suggest that networks would collapse axially when subject to shear stress. This coupling of axial and shear deformations can have particularly important consequences for extracellular matrices and collagenous tissues. Although measurements of uniaxial moduli have been made on biopolymer gels, these have not directly been related to the shear response. Here, we report measurements and simulations of axial and shear stresses exerted by a range of hydrogels subjected …

Transcranial Laser Stimulation Improves Human Cerebral Oxygenation, Fenghua Tian, Snehal Niwrutti Hase, F. Gonzalez-Lima, Hanli Liu

Bioengineering Faculty Publications - Archive

Transcranial laser stimulation of the brain with near-infrared light is a novel form of non-invasive photobiomodulation or low-level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near-infrared spectroscopy (fNIRS).

In Vitro Formation Of Neuroclusters In Microfluidic Devices And Cell Migration As A Function Of Stromal-Derived Growth Factor 1 Gradients, Sean Mccutcheon, Uchenna Unachukwu, Ankush Thakur, Robert Majeska, Stephen Redenti, Maribel Vazquez

Publications and Research

Central nervous system (CNS) cells cultured in vitro as neuroclusters are useful models of tissue regeneration and disease progression. However, the role of cluster formation and collective migration of these neuroclusters to external stimuli has been largely unstudied in vitro. Here, 3 distinct CNS cell types, medulloblastoma (MB), medulloblastoma-derived glial progenitor cells (MGPC), and retinal progenitor cells (RPC), were examined with respect to cluster formation and migration in response to Stromal-Derived Growth Factor (SDF-1). A microfluidic platform was used to distinguish collective migration of neuroclusters from that of individual cells in response to controlled concentration profiles of SDF-1. Cell …

Supernormal Conduction And Suppression Of Spatially Discordant Alternans Of Cardiac Action Potentials, Linyuan Jing, Anuj Agarwal, Abhijit R. Patwardhan

Biomedical Engineering Faculty Publications

Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate …

Pulmonary Patency Stent, Kranthidhar Bathula, Suraj Kandalam, Akhil Kolluri, Roshni Malik

Capstone Design Expo Posters

Patients with malignancies in the central airways often experience significant breathing difficulties due to occlusion of the airways. One common palliative treatment option for this is a stent placement procedure. While patients often experience immediate symptom relief, long term use can result in the formation of granulation tissue, causing restenosis of the airway. The objective of this project is to design and prototype a modification to the Boston Scientific Ultraflex partially-covered stent in order to reduce granulation tissue and maintain airway patency. Deliverables include the detailed design, a working prototype, and supporting data. The main product specifications include effectiveness in …

Design Of A Drug Delivery System Through The Gastrointestinal Tract, Kaixin Chen, Adel Husayni, Kayvon Mobarakeh, Ankit Soni

Capstone Design Expo Posters

Alzheimer’s Disease (AD) afflicts an estimated 5.3 million individuals and is the sixth leading cause of death in America. The drug delivery method of interest is an orally administered sustained-release delivery system that addresses the needs of the associated patient population. By augmenting drug delivery with a higher effective payload per dose compared to current methods, drug efficacy and bioavailability would improve. This will result in a decrease of the overall cost for medication as a greater percentage of the administered drug will be viable.

This design addresses the release of AD drug from the drug delivery system at the …

Suture Trainer: Improving Tissue Handling Technique, Albara Elshaer, Sindora Baddam, Veronica Peterkin, Millie Shah

Capstone Design Expo Posters

Tissue handling is fundamental to performing mechanical tasks of suturing and surgery on live humans and animals. While the mechanics of suturing can be taught, there is no available simulation product designed to specifically teach tissue handling skills. It is important as a future medical professional to gain better tissue handling skills in order to prevent unnecessary injury to the tissue via scarring. The suture trainer focuses on providing feedback in order to standardize tissue handling technique in order to prevent poor habits from developing. Our project deliverables included a model, working prototype, and test data collected from practicing physicians …

A Tilting System For Powered Wheelchairs, Liam Cornwall, Brandon Heath, Justin Mcdaniel, Alexander Stevenson

Capstone Design Expo Posters

The objective of our project is to create a wheelchair platform that can tilt a power wheelchair and its user back into a nearhorizontal position. The purpose of this is to allow a dentist to work on the patient in the manner and position with which they are most accustomed.

The device currently used by our sponsor, The Virginia Home, is the Versatilt platform. The Versatilt is capable of lifting a maximum weight of 750 lbs. and tilting patients back, up to 65 degrees. However, the platform is too small to accept the power wheelchairs used by the majority of …

Mri Hip Joint Traction Device, Rawan Alfadly, Carla Gomez, Sara Um

Capstone Design Expo Posters

Radiologists commonly use contrast agents to improve resolution and acuity when employing MRI (Magnetic Resonance Imaging). Introducing MRI contrast agents to the tissue in the innermost part of the femoroacetabular joint is extremely difficult because the anatomy prevents the contrast agents from infiltrating those surfaces. Therefore, getting the ideal image resolution and making diagnosis of the hip is difficult. The objective was to design a product that would successfully distract one hip joint while also stabilizing the patient’s pelvis to improve visualization so that physicians are able to better diagnose the hip. The deliverables included a preliminary model that illustrates …

Marsupialization Catheter, Hamdi Abdeen, Ananya Mishra, Lucas Olson, Jacqueline Pinderski

Capstone Design Expo Posters

A significant issue among oral and maxillofacial surgeons is the treatment of cysts within the jaw. Cysts develop at random and in most cases asymptomatically. Therefore, they may reach enormous sizes before being diagnosed. Large cysts can cause severe damage to teeth and the surrounding bone. Doctors treat small cysts by surgically removing them. However, this approach is not ideal for large cysts due to the risk of surgical complications, the high expenses incurred, and the fact that it is often undesired by the patient. Current treatments include surgically opening the cyst and either suturing the tissue open or placing …