Biomedical Engineering and Bioengineering Commons^™

Matrix-Bound Tenascin-C Directs Neuronal Differentiation Through Stiffness-Tuned Meha Hydrogels Mimicking The Spinal Cord Microenvironment, Rounak Pokharel, Vasanti Dhakate, Jessica Onyak, Elif Ertugral, Chandrasekhar R. Kothapalli, Nic D. Leipzig

Chemical & Biomedical Engineering Faculty Publications

Spinal cord injury (SCI) leads to a complex remodeling of the extracellular matrix (ECM), where Tenascin-C (TNC) is strongly upregulated during the early phases of the injury cascade. While TNC is known to influence neural cell behavior, its functional role and mode of presentation in guiding neuronal differentiation remains unclear. In this study, we developed a stiffness-controlled methacrylated hyaluronic acid (MeHA) hydrogel platform that mimics the mechanical properties of the spinal cord and enables defined matrix immobilization of TNC. In vivo analyses showed elevated TNC expression from day 1, with the strongest perilesional signal during the subacute period (1 week-1 …

Hyaluronan 35 Prevents Endotoxin-Mediated Dysregulated Skeletal Muscle Proteostasis During Ethanol Exposure, Nicole Welch, Pugazhendhi Kannan, Gangarao Davuluri, Annette Bellar, Amy H. Attaway, Saurabh Mishra, Jasmin A. Cunningham, Avinash Kumar, Ryan Musich, Elif G. Ertugral, Vandana Agrawal, Isaac L. Hu, Terri J. Hartford, Noah L. Weisleder, Vidula T. Vachharajani, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Sarcopenia in alcohol-related liver disease (ALD) is of high clinical significance, but there are no effective treatments. Hyaluronan 35 kDa (HA35), a glycosaminoglycan polymer, modulates responses to Toll-like receptor 4 (TLR4), a lipopolysaccharide receptor, to improve hepatic and macrophage function in ALD. We evaluated skeletal muscle responses to HA35 in preclinical models of ALD. Responses to ethanol, lipopolysaccharide (LPS), and HA35 were studied in differentiated murine C2C12/human-induced pluripotent stem cell (hiPSC)-derived myotubes, and wild-type/HA receptor CD44 knockout (CD44(-/-)) mouse models of ALD (mALD). Signaling molecules and measures of protein homeostasis (proteostasis) were quantified by immunoblots, mitochondrial oxidative function was determined …

Numerical Investigation Of A Dual-Mode Shape Memory Alloy Stent Enabling Secondary Expansion Via Focused Ultrasound: A Potential Strategy For Correcting In-Stent Restenosis, Stephen Asare, Lucinda Duncan, Josiah Owusu-Danquah, Brian L. Davis

Civil and Environmental Engineering Faculty Publications

Coronary stent implantation is an invasive procedure performed to correct atherosclerosis. The aftermath of this procedure is identified with neointimal hyperplasia, which contributes to in-stent restenosis (ISR), and thus remains a significant clinical challenge. This study introduces a novel, noninvasive conceptual approach for addressing ISR through the thermal activation of shape memory alloy (SMA) stent using focused ultrasound (FU) in a controlled manner to restore luminal patency. COMSOL Multiphysics and ABAQUS finite element software were employed to perform the numerical modeling to simulate the thermal and mechanical responses of the SMA stent integrated into the arterial wall. After 15 s …

Development Of Gelma-Based Hydrogel Scaffolds With Tunable Mechanical Properties For Applications In Peripheral Nerve Regeneration, Kylie M. Schmitz, Tanner L. Larson, Michael W. Borovich, Xianfang Wu, Geyou Ao, Megan Jack, Liqun Ning

Chemical & Biomedical Engineering Faculty Publications

Peripheral nerve injuries (PNIs) have a significant impact on the quality of life for patients suffering from trauma or disease. In injuries with critical nerve gaps, PN regeneration requires tissue scaffolds with appropriate physiological properties that promote cell growth and functions. Hydrogel scaffolds represent a promising platform for engineering soft tissue constructs that meet key physiological requirements. Nonetheless, ongoing innovation remains essential, as current designs continue to fall short of replicating the functional performance of autografts in bridging critical-sized nerve defects. In this study, gelatin methacrylate (gelMA)-based hydrogels are evaluated to fully characterize their pore structure, compressive stiffness, viscoelasticity, and …

Tunable Methacrylated Decellularized Heart Matrix: A Versatile Scaffold For Cardiac Tissue Engineering, Valinteshley Pierre, Douglas H. Wu, Chao Liu, Elif Ertugral, Chandrasekhar R. Kothapalli, Samuel E. Senyo

Chemical & Biomedical Engineering Faculty Publications

Therapeutic tissue regeneration remains a significant unmet need in heart failure and cardiovascular disease treatment, which are among the leading causes of death globally. Decellularized heart matrix (DHM) offer promising advantages for tissue engineering, including low immunogenicity and seamless integration into biological processes, facilitating biocompatibility. However, DHM is challenged by weak mechanical properties that limit its utility to biomedical applications like tissue engineering. To address this limitation, we functionalized DHM with methacryloyl functional groups (DHMMA) that support UV-induced crosslinking to enhance mechanical properties. By modulating the degree of methacryloyl substitution, a broad range of stiffness was achieved while maintaining cell …

Personalized Bioceramic Grafts For Craniomaxillofacial Bone Regeneration, Ana Beatriz G. De Carvalho, Maedeh Rahimnejad, Rodrigo L. M. S. Oliveira, Prabaha Sikder, Guilherme S. F. A. Saavedra, Et. Al.

Mechanical Engineering Faculty Publications

The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue …

Methods For Objective Determination Of Musculoskeletal Coordinate Systems, Tara Francesca Nagle

ETD Archive

Joint mechanics research relies on joint kinematics and kinetics measurements, represented from relative relationships of local coordinate systems (CS) belonging to bones of the joint. It’s common to define these CSs from anatomical landmarks, which are sensitive to observer variability and often don’t result in CS that best represent the functional motion of the joint. This work is presented in three articles addressing the following aims: 1) to develop a method to objectively define coordinate systems through optimization of unique passive movement paths, 2) to develop an alternative method to objectively define coordinates systems for joints with non-unique passive movement …

Influence Of Ligament Locations And Activity Profiles On Risk Of Knee Injury In Adolescents, Alexandria Mallinos

ETD Archive

The Anterior Cruciate Ligament (ACL) is the most commonly injured ligament in the body. The overall goal of this project is to develop patient-specific computational pediatric knee models that can accurately predict the in vivo biomechanical environment of the ACL. The foundation of this research is broken down into three specific parts: 1) model construction, 2) model validation, and 3) model application.

Specific Aim #1 developed anatomically accurate specimen-specific finite element representations of pediatric tibiofemoral joints. The models were able to demonstrate the ability for the Open Knee cruciate stereolithography (stl) files to be three-dimensional scaled to create subject-specific ligaments …

Site-Specific Glyco-Engineering Of Recombinant Thrombomodulin, Joseph M. Keil

ETD Archive

Thrombomodulin (TM), a membrane glycoprotein predominately expressed on endothelium, plays essential roles in regulating local hemostatic balance. Particularly, TM modulates the activity of thrombin from a procoagulant to an anticoagulant protease. When bound to TM, thrombin activates plasma protein C, which selectively inactivates coagulation factors Va and VIIIa. At the same time, TM-bound thrombin is unable to cleave fibrinogen or to activate platelets diminishing its procoagulant activity. recombinant TM456 is a promising anticoagulant candidate, but it has a very short half-life. TM is a proteoglycan and its O-linked glycosaminoglycan (GAG), chondroitin sulfate (CS), on the D3 domain contributes to TM’s …

Motion Analysis Of Feeding Tasks: Brachial Plexus Versus Control Subjects, Madison M. Lovette

ETD Archive

Brachial plexus birth injuries (BPBI) occur in about 0.4 to 4.6 of every 1000 live births due to stretching or tearing of the nerves. Children with BPBI often struggle to perform daily living activities without assistance, including feeding themselves. Upper extremity function is commonly assessed in children with BPBI using the modified Mallet classification, a set of positions representing activities of daily living that are scored according to ability. The hand to mouth position is a Mallet position and is often used to represent feeding tasks in the BPBI population. Establishing this normative data will provide a baseline for comparison …

Predictions Of Indentation Stiffness Of Musculoskeletal Regions Using Ultrasound, Sean Doherty

ETD Archive

Tissue indentation response is an important metric for understanding how different musculoskeletal regions respond to loading and is a function of the tissue’s form. Modem imaging techniques provide information about the internal structures of human tissue. Ultrasound remains one of the most common imaging techniques performed, given its portability and low costs. Prior work and data collection on 100 patients involved the collection of ultrasound images at eight different locations across the musculoskeletal extremities. Given the tissue structure information that the medical imaging provided, it was hypothesized that the mechanical properties of the tissue could be predicted from this data. …

Lipids Affect The Diffusion Of Estradiol In Osteonal Bone, Nicholas Anthony Cimino

ETD Archive

In healthy osteonal bone, embedded osteocytes form an intercellular communication network through overlapping cell membrane extensions, possibly defining an overlooked and clinically relevant lipid-mediated transport pathway for nonpolar molecules. Previous techniques evaluating solute transport in cortical bone limit tissue analysis to microscale areas (less than 1 mm2) using tracers and assumptions that diminish clinical relevance, presenting the need for an improved method to evaluate solute diffusion in macroscale areas (greater than 1 mm2) of osteonal bone. A new diffusion system - constructed of glass and polytetrafluoroethylene - was designed and validated for this purpose, exhibiting minimal adsorption of solutes and …

Percutaneous-Reinforced Osteoplasty: A Review Of Emerging Treatment Strategies For Bone Interventions, Nischal Koirala, Jyotsna Joshi, Stephen F. Duffy, Gordon Mclennan

Civil and Environmental Engineering Faculty Publications

Percutaneous-reinforced osteoplasty is currently being investigated as a possible therapeutic procedure for fracture stabilization in high-risk patients, primarily in patients with bone metastases or osteoporosis. For these patients, a percutaneous approach, if structurally sound, can provide a viable method for treating bone fractures without the physiologic stress of anesthesia and open surgery. However, the low strength of fixation is a common limitation that requires further refinement in scaffold design and selection of materials, and may potentially benefit from tissue-engineering-based regenerative approaches. Scaffolds that have tissue regenerative properties and low inflammatory response promote rapid healing at the fracture site and are …

An Improved Polynomial Chaos Expansion Based Response Surface Method And Its Applications On Frame And Spring Engineering Based Structures, Mhd A. Hafez

ETD Archive

In engineering fields, computational models provide a tool that can simulate a real world response and enhance our understanding of physical phenomenas. However, such models are often computationally expensive with multiple sources of uncertainty related to the model’s input/assumptions. For example, the literature indicates that ligament’s material properties and its insertion site locations have a significant effect on the performance of knee joint models, which makes addressing uncertainty related to them a crucial step to make the computational model more representative of reality. However, previous sensitivity studies were limited due to the computational expense of the models. The high computational …

Role Of Inflammatory Niche And Adult Cardiomyocyte Coculture On Differentiation, Matrix Synthesis, And Secretome Release By Human Bone Marrow Mesenchymal Stem Cells, Jyotsna Joshi, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Myocardial infarction (MI) causes cardiomyocyte death, provokes innate immune response, and initiates tissue remodeling. The intrinsic healing process is insufficient to replace the lost cells, or regenerate and restore the functional features of the native myocardium. Autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation is being explored to offer therapeutic potential after MI. Here, we cultured human BM-MSC spheroids in three-dimensional collagenous gels for 28 days under exposure to tumor necrosis factor-alpha (+ TNFα), and coculture with adult human cardiomyocytes, or with conditioned media (CM) pooled from TNFα-stimulated adult cardiomyocytes. MSC differentiation marker (CD90, GATA4, cTnI, cTnT, Cx43, MHC, α-actin) …

Implementation Of Microfluidic Mixers For The Optimization Of Polymeric, Gold, And Perovskite Nanomaterials Synthesis, Alexa Roberts

ETD Archive

I would like to thank Dr. Chandra Kothapalli for the opportunity to participate in this research project and the continuous guidance he has given me in all aspects of the lab work. I would like to acknowledge the entire Chemical and Biomedical Engineering Department for their assistance throughout the program, for partially supporting my tuition and stipend through teaching assistantships, and the opportunities to present and discuss my research project with other interested students and faculty. I would like to acknowledge Dr. Petru Fodor and Dr. Geyou Ao for their support as members of my defense committee. Additionally, I would …

Interaction Between The Metabolism Of Ketone Bodies In Brain Tissue And Neurological Disorders, Chan-Chih Hsiao

ETD Archive

Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain tissue. A computational model of the biochemical pathways in brain is presented in this paper. The model structure consists of neurons, astrocytes, and a surrounding capillary network. Glucose is the major oxidative energy substrate in the brain. However, under hypoglycemic conditions such as during diet or fasting …

Developing A Multifunctional Thermo-Responsive Viral Like Particle (Vlp) Platform With New Physicochemical Characteristics, Sepehr Dejdar

ETD Archive

Smart materials are a class of material whose physical characteristics change significantly in a controllable fashion once exposed to an external stimulus such as stress, pH, light, temperature, etc. If the temperature is the external stimuli (control variable) the material is termed thermo-responsive. Out of numerous thermo-responsive materials, elastin-like polypeptide (ELP) is a well-known protein-based biopolymer. Protein cages are well-defined biological nanostructures which are highly symmetrical and monodisperse. This class of proteins are both chemically and genetically tunable, making them a suitable recipient of new properties. Protein re-engineering is the basis of developing a hybrid platform (e.g. polymer-protein) to deliver …

Spark Plasma Sintering Of Low Modulus Titanium-Niobium-Tantalum-Zirconium (Tntz) Alloy For Biomedical Applications, Nicholas Mavros, Taban Larimian, Javier Esqivel, Rajeev Kumar Gupta, Rodrigo Contieri, Tushar Borkar

Mechanical Engineering Faculty Publications

In metallurgy, titanium has been a staple for biomedical purposes. Its slow toxicity and alloying versatility make it an attractive choice for medical applications. However, studies have shown the difference in elastic modulus between titanium alloys (116 GPa) and human bone (10–40 GPa), which contributes to long term issues with loose hardware fixation. Additionally, long term studies have shown elements such as vanadium and aluminum, which are commonly used in Ti-6Al-4V biomedical alloys, have been linked to neurodegenerative diseases like Alzheimer and Parkinson. Alternative metals known to be less toxic are being explored as replacements for alloying elements in titanium …

Synthesis And Secretome Release By Human Bone Marrow Mesenchymal Stem Cell Spheroids Within Three-Dimensional Collagen Hydrogels: Integrating Experiments And Modelling, Jyotsna Joshi, Mohammadreza Dehghan Abnavi, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Myocardial infarction results in loss of cardiac cell types, inflammation, extracellular matrix (ECM) degradation, and fibrotic scar. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) is being explored as they could differentiate into cardiomyocyte-like cells, integrate into host tissue, and enhance resident cell activity. The ability of these cells to restore lost ECM, remodel the inflammatory scar tissue, and repair the injured myocardium remains unexplored. We here elucidated the synthesis and deposition of ECM (e.g., elastin, sulfated glycosaminoglycans, hyaluronan, collagen type III, laminin, fibrillin, lysyl oxidase, and nitric oxide synthases), matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), and other secretome …

Biophysical And Biomechanical Properties Of Neural Progenitor Cells As Indicators Of Developmental Neurotoxicity, Gautam Mahajan, Moo-Yeal Lee, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Conventional in vitro toxicity studies have focused on identifying IC50 and the underlying mechanisms, but how toxicants influence biophysical and biomechanical changes in human cells, especially during developmental stages, remain understudied. Here, using an atomic force microscope, we characterized changes in biophysical (cell area, actin organization) and biomechanical (Young's modulus, force of adhesion, tether force, membrane tension, tether radius) aspects of human fetal brain-derived neural progenitor cells (NPCs) induced by four classes of widely used toxic compounds, including rotenone, digoxin, N-arachidonoylethanolamide (AEA), and chlorpyrifos, under exposure up to 36 h. The sub-cellular mechanisms (apoptosis, mitochondria membrane potential, DNA damage, glutathione …

Three-Dimensional Human Neural Stem Cell Culture For High-Throughput Assessment Of Developmental Neurotoxicity, Pranav Joshi

ETD Archive

Only a few hundred of compounds, among tens of thousands of commercially available compounds, have been tested for developmental neurotoxicity (DNT) due to the limitations of current guidelines for DNT which are based entirely on in vivo experiments. In vivo studies are highly expensive and time-consuming, which often do not correlate to human outcomes. There is a key gap in our ability to predict in vivo outcomes accurately and robustly using in vitro assays. This is particularly the case for predicting the toxicity of chemicals on the developing human brains. Conventional in vitro assays are typically performed in two-dimensional (2D) …

Thenar Muscle And Transverse Carpal Ligament Relationship, Jeremy Granieri Loss

ETD Archive

The transverse carpal ligament (TCL) acts as a partial origin for the thenar muscles (abductor pollicis brevis (APB), flexor pollicis brevis (FPB), opponens pollicis (OPP)). The attachment between the thenar muscles and TCL implies a relationship between the tissues. The thenar muscles rely on their origins for thumb motion and force production. However, individual thenar origin information is lacking. Further information regarding the anatomical relationship between the individual thenar muscles and TCL may provide insight into thenar muscle function. In addition, the TCL responds to thenar muscle contraction as shown by volar migration of the TCL during various thumb movements. …

Measurement Of Red Blood Cell Oxygenation State By Magnetophoresis, Nina A. Smith

ETD Archive

Magnetophoresis of red blood cells (RBCs) at varying partial pressures of oxygen (pO2) is hypothesized to rejuvenate stored blood to be utilized beyond the FDA regulated 42-day storage time. Magnetophoresis is a particle or cells motion induced by an applied magnetic field in a viscous media. The average magnetophoretic mobility of an oxygenated RBC is -0.126x10-6 mm3-s/kg, and a deoxygenated RBC is 3.66x10-6 mm3-s/kg, presenting magnetophoresis as a resource for RBC rejuvenation in hopes of storing it longer than 42 days. The main objective of this paper was to determine if controlling the pO2 within an RBC suspension, can singly- …

Compensation For Inertial And Gravity Effects In A Moving Force Platform, Sandra K. Hnat, Ben J.H. Van Basten, Antonie J. Van Den Bogert

Mechanical Engineering Faculty Publications

Force plates for human movement analysis provide accurate measurements when mounted rigidly on an inertial reference frame. Large measurement errors occur, however, when the force plate is accelerated, or tilted relative to gravity. This prohibits the use of force plates in human perturbation studies with controlled surface movements, or in conditions where the foundation is moving or not sufficiently rigid. Here we present a linear model to predict the inertial and gravitational artifacts using accelerometer signals. The model is first calibrated with data collected from random movements of the unloaded system and then used to compensate for the errors in …

Modeling Liver Diseases Using Hepatic Cell Microarrays, Alexander David Roth

ETD Archive

Hepatocellular carcinoma (HCC) is an invasive and aggressive cancer of the liver that arises due to chronic cirrhosis. Research into understanding HCC has focused on two-dimensional (2D) and three-dimensional (3D) technologies to simulate the liver microenvironment and use animal models to model how HCC affects the rest of the body. 3D hydrogel models are desired because they can mimic the transport behavior observed in vivo by structurally mimicking the extracellular matrix (ECM) without the ethical concerns of animal models. However, hydrogels can be toxic to cells and require optimal procedures for appropriate handling. In this study, we created 3D models …

Advanced Manufacturing Of Titanium Alloys For Biomedical Applications, Nicholas C. Mavros

ETD Archive

In metallurgy, Titanium has been a staple for biomedical purposes. Its low toxicity and alloying versatility make it an attractive choice for medical applications. However, studies have shown the difference in elastic modulus between Titanium alloys (116 GPa) and human bone (40-60 GPa) contribute to long term issues with loose hardware fixation. Additionally, long term studies have shown elements such as Vanadium and Aluminum, which are commonly used in Ti-6Al-4V biomedical alloys, have been linked to neurodegenerative diseases like Alzheimers and Parkinsons. Alternative metals known to be less toxic are being explored as replacements for alloying elements in Titanium alloys. …

Implementation Of A Reverse Staggered-Herringbone Microfluidic Mixer For High-Throughput Polymeric Nanoparticles Synthesis, Alexa Roberts

Undergraduate Research Posters 2018

The goal of this research is to implement and optimize the operating conditions of a microfluidic mixer to synthesize polymeric nanoparticles (NPs) in a high-throughput fashion. Using a reverse staggered-herringbone microfluidic mixer that we recently designed, the effects of experimental conditions such as flowrate and reactant composition on NP characteristics were investigated and optimized. The device design allowed for physical contact between two streams of fluids – one containing poly(lactic-co-glycolic acid; PLGA) in acetonitrile and the other deionized water, to allow for efficient mixing and NP precipitation to occur. The resulting NPs were characterized using dynamic light scattering (DLS) and …

Prediction Of Metabolism-Induced Neurotoxicity On A 384pillarplate, Rushabh Patel, Pranav Joshi, Soo-Yeon Kang, Stephen Hong, Parnian Bigdelou

Undergraduate Research Posters 2018

Metabolism of compounds including neurotoxins primarily occurs in the liver by a variety of drug-metabolizing enzymes (DMEs) followed by a series of downstream responses. Unmodified (or parent) neurotoxins are transported into human hepatocytes through several influx transporters or via passive diffusion and undergo Phase I and Phase II biotransformation by DMEs before they are cleared. Neurotoxins and their metabolites generated from human hepatocytes could potentially lead to the toxic effects on neural stem cells (NSCs) as the reactive metabolites have potential for producing reactive oxygen species (ROS), which can lead to irreversible oxidative damage to NSCs via lipid peroxidation, DNA, …

Dendrite Morphology Of Pb-5.8 Sb Alloy: Gradient Freeze Ds With Cross-Section Area Change, Michael Shannon

Undergraduate Research Posters 2018

Directional solidification (DS) is the process of solidifying a metal alloy from one end to another resulting in aligned primary dendrites which are branched tree like features. Alignment of primary dendrites along [100] direction and their uniformity and distribution along the DS length determines the mechanical properties. These properties are especially important for single crystal turbine blade applications in modern gas turbine engines. Convection during solidification plays an important role in formation of detrimental defects, such as, misaligned grains, non-uniformity of dendrites and composition inhomogeneity. In this study the microstructural evolution during “Gradient Freeze DS process”, involving an abrupt cross-section …