Biomedical Engineering and Bioengineering Commons^™

Shipboard Design And Fabrication Of Custom 3d-Printed Soft Robotic Manipulators For The Investigation Of Delicate Deep-Sea Organisms, Daniel M. Vogt, Kaitlyn P. Becker, Brennan T. Phillips, Moritz A. Graule, Randi D. Rotjan, Timothy M. Shank, Erik E. Cordes, Robert J. Wood, David F. Gruber

Publications and Research

Soft robotics is an emerging technology that has shown considerable promise in deep-sea marine biological applications. It is particularly useful in facilitating delicate interactions with fragile marine organisms. This study describes the shipboard design, 3D printing and integration of custom soft robotic manipulators for investigating and interacting with deep-sea organisms. Soft robotics manipulators were tested down to 2224m via a Remotely-Operated Vehicle (ROV) in the Phoenix Islands Protected Area (PIPA) and facilitated the study of a diverse suite of soft-bodied and fragile marine life. Instantaneous feedback from the ROV pilots and biologists allowed for rapid re-design, such as adding ªfingernailsº, …

A Novel Multiscale Mathematical Model For Building Bone Substitute Materials For Children, Abdennasser Chekroun, Laurent Pujo-Menjouet, Jean-Philippe Berteau

Publications and Research

Bone is an engineering marvel that achieves a unique combination of stiffness and toughness exceeding that of synthesized materials. In orthopedics, we are currently challenged for the child population that needs a less stiff but a tougher bone substitute than adults. Recent evidence suggests that the relationship between inter-molecular connections that involve the two main bone building blocks, TropoCollagen molecules (TC) and carbonated Hydroxyapatite (cAp), and bone macroscopic mechanical properties, stiffness and toughness, are key to building bone substitute materials for children. The goal of our study is to establish how inter-molecular connections that occur during bone mineralization are related …

Engaging Biomedical Engineering In Health Disparities Challenges, Maribel Vazquez

Publications and Research

Health Disparities (HD) are community-based, biomedical challenges in need of innovative contributions from Science, Technology, Engineering and Math (STEM) fields. Surprisingly, STEM professionals demonstrate a persistent lack of HD awareness and/or engagement in both research and educational activities. This project introduced Health Disparities (HD) as technical challenges to incoming undergraduates in order to elevate engineering awareness of HD. The objective was to advance STEM-based, HD literacy and outreach to young cohorts of engineers. Engineering students were introduced to HD challenges in technical and societal contexts as part of Engineering 101 courses. Findings demonstrate that student comprehension of HD challenges increased …

Collective Adhesion And Displacement Of Retinal Progenitor Cells Upon Extracellular Matrix Substrates Of Transplantable Biomaterials, Ankush Thakur, Shawn Mishra, Juan Pena, Jing Zhou, Stephen Redenti, Robert Majeska, Maribel Vazquez

Publications and Research

Strategies to replace retinal photoreceptors lost to damage or disease rely upon the migration of replacement cells transplanted into sub-retinal spaces. A significant obstacle to the advancement of cell transplantation for retinal repair is the limited migration of transplanted cells into host retina. In this work, we examine the adhesion and displacement responses of retinal progenitor cells on extracellular matrix substrates found in retina as well as widely used in the design and preparation of transplantable scaffolds. The data illustrate that retinal progenitor cells exhibit unique adhesive and displacement dynamics in response to poly-l-lysine, fibronectin, laminin, hyaluronic acid, and Matrigel. …

Review Of Emerging Approaches In Non- Or Minimally Invasive Glucose Monitoring And Their Application To Physiological Human Body Fluids, Sunghoon Jang, Chen Xu

Publications and Research

The frequent blood glucose monitoring by the diabetics and physicians is a very essential step in the management of the diabetes because this devastating disease can lead the patients to blindness, kidney disease, nervous & circulatory system disease, limb amputations, stroke and cardiovascular disease (CVD). There have been numerous attempts to develop viable painless non- or minimally invasive blood glucose monitoring techniques over the last five decades in order to replace all existing methods of home blood glucose monitoring require drawing a blood sample by piercing the skin. This review describes the principles of two main emerging general technologies such …

Inhibition Of Apoptosis Exacerbates Fatigue-Damage Tendon Injuries In An In Vivo Rat Model, R. Bell, M. A. Robles-Harris, M. Anderson, D. Laudier, M. B. Schaffler, E. L. Flatow, N. Andarawis-Puri

Publications and Research

Tendinopathy is a common and progressive musculoskeletal disease. Increased apoptosis is an end-stage tendinopathy manifestation, but its contribution to the pathology of the disease is unknown. A previously established in vivo model of fatigue-damage accumulation shows that increased apoptosis is correlated with the severity of induced tendon damage, even in early onset of the disease, supporting its implication in the pathogenesis of the disease. Consequently, this study aimed to determine: (1) whether apoptosis could be inhibited after fatigue damage and (2) whether its inhibition could lead to remodeling of the extracellular matrix (ECM) and pericellular matrix (PCM), to ultimately improve …

Thermoresponsive, Redox-Polymerized Cellulosic Hydrogels Undergo In Situ Gelation And Restore Intervertebral Disc Biomechanics Post Discectomy, Devika Varma, H. A. Lin, R. G. Long, G. T. Gold, A. C. Hecht, J. C. Iadridis, Steven B. Nicoll

Publications and Research

Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors. Thermogelling MC was required to enable consistent and timely …

A Gal-Ms Device To Evaluate Cell Migratory Response To Combined Galvano-Chemotactic Fields, Shawn Mishra, Maribel Vazquez

Publications and Research

Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS), spinal cord repair and tumor treating fields (TTF). The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, …

Decreased Triple Network Connectivity In Patients With Recent Onset Post-Traumatic Stress Disorder After A Single Prolonged Trauma Exposure, Yang Liu, Liang Li, Baojuan Li, Na Feng, Lihong Li, Xi Zhang, Hongbing Lu, Hong Yin

Publications and Research

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With an arterial spin labeling sequence, three networks were first identified using independent component analysis among 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. Then, the triple network connectivity was …

The Influence Of The Electrode Dimension On The Detection Sensitivity Of Electric Cell–Substrate Impedance Sensing (Ecis) And Its Mathematical Modeling, Xudong Zhang, William Wang, Anis Nurashikin Nordin, Fang Li, Sunghoon Jang, Ioana Voiculescu

Publications and Research

Detection sensitivity is a crucial criterion in the design and application of ECIS sensors. The influence of sensing electrode dimension on detection sensitivity is investigated in this paper. Eight types of ECIS sensors were fabricated, and their experimental results reveal that smaller-radius working electrodes generate more sensitive impedance shift to cell density change. Also, the smaller radius of working electrodes yield higher impedance values, which improves signal-to-noise ratio. In a range from 1.0 mm to 3.5 mm, the distance between the working and counter electrodes does not affect impedance measurements. However, the distance should be large enough to prevent the …

Chelator-Free Radiolabeling Of Serrs Nanoparticles For Whole-Body Pet And Intraoperative Raman Imaging, Matthew A. Wall, Travis Shaffer, Stefan Harmsen, Darjus-Felix Tschaharganeh, Chun-Hao Huang, Scott W. Lowe, Charles Michael Drain, Moritz F. Kircher

Publications and Research

A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright SERRS nanoparticles with a suitable radiotracer would enable pre-operative identification of regions of interest with whole body imaging that can be rapidly corroborated with a Raman imaging device or handheld Raman scanner in order to provide high precision guidance during surgical procedures. Here we present a straightforward new method that produces radiolabeled SERRS nanoparticles for …

Insights Into The Binding Mode Of Mek Type-Iii Inhibitors. A Step Towards Discovering And Designing Allosteric Kinase Inhibitors Across The Human Kinome, Zheng Zhao, Lei Xie, Philip E. Bourne

Publications and Research

Protein kinases are critical drug targets for treating a large variety of human diseases. Type- III kinase inhibitors have attracted increasing attention as highly selective therapeutics. Thus, understanding the binding mechanism of existing type-III kinase inhibitors provides useful insights into designing new type-III kinase inhibitors. In this work, we have systematically studied the binding mode of MEK-targeted type-III inhibitors using structural systems pharmacology and molecular dynamics simulation. Our studies provide detailed sequence, structure, interaction-fingerprint, pharmacophore and binding-site information on the binding characteristics of MEK type-III kinase inhibitors. We hypothesize that the helix-folding activation loop is a hallmark allosteric binding site …

Toward Measuring Network Aesthetics Based On Symmetry, Zengqiang Chen, Matthias Dehmer, Frank Emmert-Streib, Abbe Mowshowitz, Yongtang Shi

Publications and Research

In this exploratory paper, we discuss quantitative graph-theoretical measures of network aesthetics. Related work in this area has typically focused on geometrical features (e.g., line crossings or edge bendiness) of drawings or visual representations of graphs which purportedly affect an observer’s perception. Here we take a very different approach, abandoning reliance on geometrical properties, and apply information-theoretic measures to abstract graphs and networks directly (rather than to their visual representaions) as a means of capturing classical appreciation of structural symmetry. Examples are used solely to motivate the approach to measurement, and to elucidate our symmetry-based mathematical theory of network aesthetics.

A Drosophila Model To Examine Collective Migration During Retinogenesis, Caroline Pena, Stephanie Zhang, Mildred Kamara, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Retinal dysfunction is often caused by aberrant neural cell migration during development. In this study, we observed the migration of neural cells of the Drosophila melanogaster after marking cells of the 3rd instar larvae with the GAL4-UAS expression system when exposed to a concentration gradient of FGF-8 through the use of a microfluidic device. The glial and neuronal cell ratio in the developing brain was determined through immunofluorescent staining and observation. In future studies, a microfluidic device that mimics the developing Drosophila brain and retina will be designed in order to better understand the biological factors that affect the migration …

Collective Behaviour In Video Viewing: A Thermodynamic Analysis Of Gaze Position, Kate Burleson-Lesser, Flaviano Morone, Paul Deguzman, Lucas C. Parra, Hernan Makse

Publications and Research

Videos and commercials produced for large audiences can elicit mixed opinions. We wondered whether this diversity is also reflected in the way individuals watch the videos. To answer this question, we presented 65 commercials with high production value to 25 individuals while recording their eye movements, and asked them to provide preference ratings for each video. We find that gaze positions for the most popular videos are highly correlated. To explain the correlations of eye movements, we model them as ªinteractionsº between individuals. A thermodynamic analysis of these interactions shows that they approach a ªcritical º point such that any …

Interaction Between The Stress Phase Angle (Spa) And The Oscillatory Shear Index (Osi) Affects Endothelial Cell Gene Expression, Ronny Amaya, Limary M. Cancel, John M. Tarbell

Publications and Research

Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle±SPA). Asynchronous flows (SPA close to -180Ê) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that …

The Effects Of Compensatory Auditory Stimulation And High-Definition Transcranial Direct Current Stimulation (Hd-Tdcs) On Tinnitus Perception - A Randomized Pilot Study, Simon Henin, Dovid Fein, Eric Smouha, Lucas C. Parra

Publications and Research

Background Tinnitus correlates with elevated hearing thresholds and reduced cochlear compression. We hypothesized that reduced peripheral input leads to elevated neuronal gain resulting in the perception of a phantom sound. Objective The purpose of this pilot study was to test whether compensating for this peripheral deficit could reduce the tinnitus percept acutely using customized auditory stimulation. To further enhance the effects of auditory stimulation, this intervention was paired with high-definition transcranial direct current stimulation (HD-tDCS).

Methods A randomized sham-controlled, single blind study was conducted in a clinical setting on adult participants with chronic tinnitus (n = 14). Compensatory auditory stimulation …

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.

Kcnq Channel Openers Reverse Depressive Symptoms Via An Active Resilience Mechanism, Allyson K. Friedman, Barbara Juarez, Stacy M. Ku, Hongxing Zhang, Rhodora C. Calizo, Jessica J. Walsh, Depish Chaudhury, Song Zhang, Angel Hawkins, David M. Dietz, James W. Murrogh, Maria Ribadeneira, Erik H. Wong, Rachael L. Neve, Ming-Hu Han

Publications and Research

Less than half of patients suffering from major depressive disorder, a leading cause of disability worldwide, achieve remission with current antidepressants, making it imperative to develop more effective treatment. A new therapeutic direction is emerging from the increased understanding of natural resilience as an active stress-coping process. It is known that potassium (Kþ) channels in the ventral tegmental area (VTA) are an active mediator of resilience. However, no druggable targets have been identified to potentiate active resilience mechanisms. In the chronic social defeat stress model of depression, we report that KCNQ-type Kþ channel openers, including FDA-approved drug retigabine (ezogabine), show …

Mesenchymal Stem Cell Fate: Applying Biomaterials For Control Of Stem Cell Behavior, Hilary J. Anderson, Jugal Kishore Sahoo, Rein V. Ulijn, Matthew J. Dalby

Publications and Research

The materials pipeline for biomaterials and tissue engineering applications is under continuous development. Specifically, there is great interest in the use of designed materials in the stem cell arena as materials can be used to manipulate the cells providing control of behavior. This is important as the ability to “engineer” complexity and subsequent in vitro growth of tissues and organs is a key objective for tissue engineers. This review will describe the nature of the materials strategies, both static and dynamic, and their influence specifically on mesenchymal stem cell fate.

P2x7r-Panx1 Complex Impairs Bone Mechanosignaling Under High Glucose Levels Associated With Type-1 Diabetes, Zeynep Seref-Ferlengez, Stephanie Maung, Mitchell B. Schaffler, David C. Spray, Sylvia O. Suadicani, Mia M. Thi

Publications and Research

Type 1 diabetes (T1D) causes a range of skeletal problems, including reduced bone density and increased risk for bone fractures. However, mechanisms underlying skeletal complications in diabetes are still not well understood.We hypothesize that high glucose levels in T1D alters expression and function of purinergic receptors (P2Rs) and pannexin 1 (Panx1) channels, and thereby impairs ATP signaling that is essential for proper bone response to mechanical loading and maintenance of skeletal integrity. We first established a key role for P2X7 receptor-Panx1 in osteocyte mechanosignaling by showing that these proteins are co-expressed to provide a major pathway for flow-induced ATP release. …

Controlled Microfluidics To Examine Growth-Factor Induced Migration Of Neural Progenitors In The Drosophila Visual System, Cade Beck, Tanya Singh, Angela Farooqi, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

BACKGROUND:

The developing visual system in Drosophila melanogaster provides an excellent model with which to examine the effects of changing microenvironments on neural cell migration via microfluidics, because the combined experimental system enables direct genetic manipulation, in vivo observation, and in vitro imaging of cells, post-embryo. Exogenous signaling from ligands such as fibroblast growth factor (FGF) is well-known to control glia differentiation, cell migration, and axonal wrapping central to vision.

NEW METHOD:

The current study employs a microfluidic device to examine how controlled concentration gradient fields of FGF are able to regulate the migration of vision-critical glia cells with and …

Predicted Molecular Signaling Guiding Photoreceptor Cell Migration Following Transplantation Into Damaged Retina, Uchenna John Unachukwu, Alice Warren, Ze Li, Shawn Mishra, Jing Zhou, Moira Sauane, Hyungsik Lim, Maribel Vazquez, Stephen Redenti

Publications and Research

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to …

Genesis And Growth Of Extracellular Vesicle-Derived Microcalcification In Atherosclerotic Plaques, Joshua D. Hutcheson, Claudia Goettsch, Sergio Bertazzo, Natalia Maldonado, Jessica L. Ruiz, Wilson Goh, Katsumi Yabusaki, Tyler Faits, Carlijn Bouten, Gregory Franck, Thibaut Quillard, Peter Libby, Masanori Aikawa, Sheldon Weinbaum, Elena Aikawa

Publications and Research

Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the …

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 …

A Model Microfluidics-Based System For The Human And Mouse Retina., Shawn Mishra, Ankush Thakur, Stephen Redenti, Maribel Vazquez

Publications and Research

The application of microfluidics technologies to the study of retinal function and response holds great promise for development of new and improved treatments for patients with degenerative retinal diseases. Restoration of vision via retinal transplantation therapy has been severely limited by the low numbers of motile cells observed post transplantation. Using modern soft lithographic techniques, we have developed the μRetina, a novel and convenient biomimetic microfluidics device capable of examing the migratory behavior of retinal lineage cells within biomimetic geometries of the human and mouse retina. Coupled computer simulations and experimental validations were used to characterize and confirm the formation …

Egf As A New Therapeutic Target For Medulloblastoma Metastasis, Jennifer Rico-Varela, Tanya Singh, Sean Mccutcheon, Maribel Vazquez

Publications and Research

Medulloblastoma (MB) is a malignant pediatric brain tumor known for its aggressive metastatic potential. Despite the well-documented migration of MB cells to other parts of the brain and spinal column, MB chemotaxis is poorly understood. Herein, we examined the in vitro migratory and cellular responses of MB-derived cells to external signaling of Epidermal Growth Factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and the stromal cellderived factors 1-alpha (SDF-1). Experiments utilized transwell assays and immunocytochemistry to identify receptor activation in MB migration, and used a microfluidic platform to examine directionality, trajectory, and gradient-dependence of motile cells. Data illustrates …

Carboxymethylcellulose Hydrogels Support Cns-Derived Tumor Cell Chemotactic Migration, Tanya Singh, Chandrasekhar Kothapalli, Devika Verma, Steven Nicoll, Maribel Vazquez

Publications and Research

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix (ECM) and the cell-ECM relationship. ECM is a complex network of molecules with distinct mechanical and biochemical characteristics. When the mechanisms that are in place to maintain ECM homeostasis are deregulated, most likely, this is the onset of cancer. The ECM becomes highly disorganized and the cell-matrix relationship changes, thus promoting alternations in cell mechanisms and metastasis. Medulloblastoma (MB) is one of the most common, malignant pediatric brain tumors in the United States. In order to gain a better understanding between the cell-ECM relationship and …

Monitoring The Progression Of Spontaneous Articular Cartilage Healing With Infrared Spectroscopy, Megan P. O'Brien, Madhuri Penmatsa, Uday Palukuru, Paul West, Xu Yang, Mathias P. G. Bostrom, Theresa Freeman, Nancy Pleshko

Publications and Research

Objective. Evaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.

Design. Bilateral osteochondral defects were generated in mature white New Zealand rabbits, and …

Contact Analysis For Coupling Of Plates And Screws In Fracture Fixation Of Cortical Bone, Gaffar Gailani, Rachid Moumni, Malek Brahimi

Publications and Research

Internal fixation is a common treatment for bone fracture. Bone fracture occurs due to different reasons such as motor vehicle accidents, falling,…etc. The treatment is performed by fixing plate and screws to the fracture site. Lack of stability of the implants (plates and screws) may lead to delay in healing or failure of treatment. Micro-motion between the implant and the bone may cause formation of fibrous tissue around the screw which will lead to implant loosening. On the other hands, firm fixing of the conventional implants (Dynamic Compression Plates) may lead to delay resorption and delay in healing. Recently, Locked …