Biomedical Engineering and Bioengineering Commons^™

Evalattai: A Holistic Approach To Evaluating Attribution Maps In Robust And Non-Robust Models, Ian E. Nielsen, Ravi Ramachandran, Nidhal Carla Bouaynaya, Hassan M. Fathallah-Shaykh, Ghulam Rasool

Henry M. Rowan College of Engineering Departmental Research

Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so finding appropriate methods for treating ocular disease has attracted lots of attention. This is especially due to the ineffectiveness of the conventional therapeutic method to deliver drugs into the interior parts of the eye, and the also presence of barriers such as tear film, blood-ocular, and blood-retina barriers. Recently, some novel techniques, such as different types of …

Chemical And Polymer Characterization Of The Potential Modes Of Degradation Of An Injectable Nucleus Pulposus Replacement Device, Antonio G. Abbondandolo

Theses and Dissertations

HYDRAFIL™ is a poly(vinyl alcohol)/poly(ethylene glycol)-based hydrogel nucleus pulposus replacement device that is injected in situ and has demonstrated efficacy in lowering the prevalence and pain associated with back. In this work, we developed a method to analyze HYDRAFIL™ polymer composition using (TGA) and characterized intermolecular bonding interactions within the hydrogel through (FTIR). To function as a permanent implant for nucleus pulposus replacement, HYDRAFIL™ must be stable when exposed to a multitude of degradation pathways, namely, thermal, chemical, and mechanical. We subjected HYDRAFIL™ to accelerated thermal and chemical degradation pathways and described compositional, physical and chemical property changes using a …

Recent Advances In Antimicrobial Peptide Hydrogels, Aryanna Copling, Maxwell Akantibila, Raaha Kumaresan, Gilbert Fleischer, Dennise Cortes, Rahul S Tripathi, Valerie J. Carabetta, Sebastian Vega

Cooper Medical School of Rowan University Departmental Research

Advances in the number and type of available biomaterials have improved medical devices such as catheters, stents, pacemakers, prosthetic joints, and orthopedic devices. The introduction of a foreign material into the body comes with a risk of microbial colonization and subsequent infection. Infections of surgically implanted devices often lead to device failure, which leads to increased patient morbidity and mortality. The overuse and improper use of antimicrobials has led to an alarming rise and spread of drug-resistant infections. To overcome the problem of drug-resistant infections, novel antimicrobial biomaterials are increasingly being researched and developed. Hydrogels are a class of 3D …

Application Of Convergent Science And Technology Toward Ocular Disease Treatment, Ayca Bal-Ozturk, Ece Ozcan-Bulbul, Hazal Ezgi Gultekin, Berivan Cecen, Ebru Demir, Atefeh Zarepout, Sibel Cetinel, Ali Zarrabi

Henry M. Rowan College of Engineering Departmental Research

Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so finding appropriate methods for treating ocular disease has attracted lots of attention. This is especially due to the ineffectiveness of the conventional therapeutic method to deliver drugs into the interior parts of the eye, and the also presence of barriers such as tear film, blood-ocular, and blood-retina barriers. Recently, some novel techniques, such as different types of …

Efficient Scopeformer: Towards Scalable And Rich Feature Extraction For Intracranial Hemorrhage Detection Using Hybrid Convolution And Vision Transformer Networks, Yassine Barhoumi

Theses and Dissertations

The field of medical imaging has seen significant advancements through the use of artificial intelligence (AI) techniques. The success of deep learning models in this area has led to the need for further research. This study aims to explore the use of various deep learning algorithms and emerging modeling techniques to improve training paradigms in medical imaging. Convolutional neural networks (CNNs) are the go-to architecture for computer vision problems, but they have limitations in mapping long-term dependencies within images. To address these limitations, the study explores the use of techniques such as global average pooling and self-attention mechanisms. Additionally, the …

Impact Of Adipose-Derived Stem Cells On Aortic Tensile Strength In A Model Of Abdominal Aortic Aneurysm, Keshav Kooragayala, Johanna Lou, Vaishali Krishnadoss, Brian Zilberman, Nicholas Deleo, Olga Ostrovsky, Ping Zhang, Iman Noshadi, Spencer Brown, Jeffrey P. Carpenter

Henry M. Rowan College of Engineering Departmental Research

Introduction: Abdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment. Methods: 16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm …

Self-Healing Properties Of Augmented Injectable Hydrogels Over Time, Connor Castro, Zachary R. Brown, Erik Brewer

Henry M. Rowan College of Engineering Departmental Research

Injectable polymers offer great benefits compared to other types of implants; however, they tend to suffer from increased mechanical wear and may need a replacement implant to restore these mechanical properties. The purpose of this experiment is to investigate an injectable hydrogel's self-healing ability to augment itself to a previously molded implant. This was accomplished by performing a tensile strength test to examine potential diminishing mechanical properties with increasing time, as well as dye penetration tests to examine the formation of interfacial bonds between healed areas of hydrogels. There were several time points in between injections that were explored, from …

Polyethyleneimine Shell Nucleic Acid Nanostructures From Gold Nanoparticle Template For Chemotherapeutic Drug Delivery, Brendan Guy Rucci

Theses and Dissertations

The next generation of anticancer agents will emerge from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA-conjugated gold nanoparticles (DNA-AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to citrate-capped AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPPs) and a high density of DNA (85 molecules/particle) containing daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7±17.3 nm and zeta potential of 20.4±3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on the surface of the particle toroidally, …

A 3d Bioprinted Hydrogel Microfluidic Device For Screening Applications, Anant Bhusal

Theses and Dissertations

The microfluidic enabled the integration of engineered miniaturized tissue models for drug screening. Conventional polydimethylsiloxane or plastic-based devices require multiple fabrication steps, which are challenging. We developed a 3D bioprinting approach to create prototypes of hydrogel-based multi-material microfluidic devices integrated with microtissue models. The approach utilizes poly(ethylene glycol) diacrylate and gelatin-methacryloyl to create microfluidic chips using multi-material bioprinting capacity with a high resolution of 15µm on x-y and 50µm on the z-axis and post-printing viability of >90%. We demonstrated easy regulation of stiffness from 24±5 kPa to 1,180±9 kPa and burst pressure from 16±1kPa to 256±19 kPa in the chip …

Wearable Sensing System For Noninvasive Monitoring Of Intracranial Biofluid Shifts In Aerospace Applications., Jacob L Griffith, Kim Cluff, Grant M Downes, Brandon Eckerman, Subash Bhandari, Benjamin E Loflin, Ryan Becker, Fayez Alruwaili, Noor Mohammed

Henry M. Rowan College of Engineering Departmental Research

The alteration of the hydrostatic pressure gradient in the human body has been associated with changes in human physiology, including abnormal blood flow, syncope, and visual impairment. The focus of this study was to evaluate changes in the resonant frequency of a wearable electromagnetic resonant skin patch sensor during simulated physiological changes observed in aerospace applications. Simulated microgravity was induced in eight healthy human participants (n = 8), and the implementation of lower body negative pressure (LBNP) countermeasures was induced in four healthy human participants (n = 4). The average shift in resonant frequency was -13.76 ± 6.49 MHz for …

Bioactive Self-Forming Hydrogels For Biomedical Applications, Kirstene Arcuino Gultian Giddings

Theses and Dissertations

Hydrogels are soft biomaterials that feature a wide range of physical and biochemical properties. Although highly versatile, hydrogels typically require an exogeneous input (e.g., light, pH, temperature) to form, and this limits their use to conditions where a catalyst is present. The goal of this dissertation is to expand the use of catalyst-based hydrogels by developing hydrogels with independently tunable properties which gel in situ without external stimuli. This new class of hydrogels was developed by first modifying macromers with norbornene (Nor) or tetrazine (Tet) moieties. Macromers containing Nor or Tet remain liquid when dissolved, and upon mixing self-form into …

Recombinant Human Plasma Gelsolin Reverses Increased Permeability Of The Blood-Brain Barrier Induced By The Spike Protein Of The Sars-Cov-2 Virus., Łukasz Suprewicz, Kiet A Tran, Ewelina Piktel, Krzysztof Fiedoruk, Paul A Janmey, Peter Galie, Robert Bucki

Henry M. Rowan College of Engineering Departmental Research

BACKGROUND: Plasma gelsolin (pGSN) is an important part of the blood actin buffer that prevents negative consequences of possible F-actin deposition in the microcirculation and has various functions during host immune response. Recent reports reveal that severe COVID-19 correlates with reduced levels of pGSN. Therefore, using an in vitro system, we investigated whether pGSN could attenuate increased permeability of the blood-brain barrier (BBB) during its exposure to the portion of the SARS-CoV-2 spike protein containing the receptor binding domain (S1 subunit).

MATERIALS AND METHODS: Two- and three-dimensional models of the human BBB were constructed using the human cerebral microvascular endothelial …

Transcriptomic Analysis Of A 3d Blood-Brain Barrier Model Exposed To Disturbed Fluid Flow., Nesrine Bouhrira, Brandon J Deore, Kiet A Tran, Peter Galie

Henry M. Rowan College of Engineering Departmental Research

Cerebral aneurysms are more likely to form at bifurcations in the vasculature, where disturbed fluid is prevalent due to flow separation at sufficiently high Reynolds numbers. While previous studies have demonstrated that altered shear stress exerted by disturbed flow disrupts endothelial tight junctions, less is known about how these flow regimes alter gene expression in endothelial cells lining the blood-brain barrier. Specifically, the effect of disturbed flow on expression of genes associated with cell-cell and cell-matrix interaction, which likely mediate aneurysm formation, remains unclear. RNA sequencing of immortalized cerebral endothelial cells isolated from the lumen of a 3D blood-brain barrier …

Histone Deacetylase 4 And 5 Translocation Elicited By Microsecond Pulsed Electric Field Exposure Is Mediated By Kinase Activity., Zahra Safaei, Gary L. Thompson Iii

Henry M. Rowan College of Engineering Departmental Research

Electroporation-based technologies using microsecond pulsed electric field (µsPEF) exposures are established as laboratory and clinical tools that permeabilize cell membranes. We demonstrate a µsPEF bioeffect on nucleocytoplasmic import and export of enzymes that regulate genetic expression, histone deacetylases (HDAC) -4 and -5. Their μsPEF-induced nucleocytoplasmic transport depends on presence and absence of extracellular calcium ions (Ca

Investigation Of Flexible And Wearable Devices For The Analysis Of Biological Signals, Muhammad Usman

Theses and Dissertations

The application potential for flexible and wearable electronics in the field of healthcare has received great interest in recent years. Flexible and wearable devices based on soft, biocompatible materials can be comfortably attached to the human skin for continuous health monitoring. In this work, we present two novel wearable bioelectrical impedance analysis (BIA) systems for body composition measurement. First, we developed a wearable ring-based BIA system for body fat monitoring. The wearable ring contains flexible copper electrodes to interface with the human body. The device is tested on 40 healthy volunteers and the results demonstrate a high correlation with an …

Biomaterials With Diverse Physical & Chemical Signals For Tissue Engineering Applications, Mohammed Mehdi Benmassaoud

Theses and Dissertations

Cells within natural tissues are exposed to a myriad of biochemical and biophysical cues, and it is challenging to recapitulate these signals in vitro. The goal of this dissertation is to create materials with distinct biophysical and biochemical signals as platforms that induce controllable yet diverse cellular responses. To evaluate the effects of heterogeneous biophysical cues on cell behavior, cells were encapsulated in porous scaffold-hydrogel composites, and it was found that cellular metrics (morphology, matrix mechanosensing) varied within soft (hydrogel) and rigid (scaffold) composite regions. To create soft materials with spatially defined biochemical signals, hydrogels that can be subsequently photopatterned …

Effects Of Cell-Cell Signaling On Mesenchymal Stem Cell Mechanosensing And Adaptation To Dynamic Material, Matthew E. Lowe

Theses and Dissertations

The goal of this research is to identify the role of engineered cell-cell signals on how cells sense material properties. Mesenchymal stem cells (MSCs) are adult cells whose behavior is regulated by matrix mechanosensing, which is characterized by stiffness-dependent changes in cell shape and the nuclear localization of mechano-transducer proteins including YAP (Yes-associated Protein). MSC area and nuclear YAP translocation increase with increasing stiffness, and although low levels of N-cadherin-based cell-cell signaling reduce this effect, two fundamental questions remain: (1) do engineered cell-cell signals at higher concentrations further reduce matrix mechanosensing, and (2) does N-cadherin signaling affect MSC adaptation to …

The Role Of Small Gtpases In Regulating Blood-Brain Barrier Mechanotransduction, Brandon Jude Deore

Theses and Dissertations

Fluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the effect of shear on the blood-brain barrier (BBB) have yet to be clarified in cerebral vasculature despite its importance for brain homeostasis.. Neurological symptoms including the formation of microclots, stroke, and other neurological pathologies associated with changes in cerebral blood flow are hallmarks of BBB dysfunction. The in vitro model used in this dissertation is compatible with real-time measurement of barrier function using a transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level …

Bioengineered Scaffolds To Induce Alignment And Promote Axon Regeneration Following Spinal Cord Injury, Kiet Anh Tran

Theses and Dissertations

Scaffolds delivered to injured spinal cords to stimulate axon connectivity often act as a bridge to stimulate regeneration at the injured area, but current approaches lack the permissiveness, topology and mechanics to mimic host tissue properties. This dissertation focuses on bioengineering scaffolds through the means of altering topology in injectables and tuning mechanics in 3D-printed constructs as potential therapies for spinal cord injury repair. A self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunohistochemistry assays verify that vascularized peptide scaffolds promote axon infiltration, attenuate inflammation and reduce astrogliosis. Furthermore, …

Injectable Hydrogel With Immobilized Bmp-2 Mimetic Peptide For Local Bone Regeneration, Kirstene A. Gultian, Roshni Ghandi, Kayla Decesari, Vineeth Romiyo, Emily P. Kleinbart, Kelsey Martin, Pietro M. Gentile, Tae Won B. Kim, Sebastian Vega

Henry M. Rowan College of Engineering Departmental Research

Osteoporosis is a disease characterized by a decrease in bone mineral density, thereby increasing the risk of sustaining a fragility fracture. Most medical therapies are systemic and do not restore bone in areas of need, leading to undesirable side effects. Injectable hydrogels can locally deliver therapeutics with spatial precision, and this study reports the development of an injectable hydrogel containing a peptide mimic of bone morphogenetic protein-2 (BMP-2). To create injectable hydrogels, hyaluronic acid was modified with norbornene (HANor) or tetrazine (HATet) which upon mixing click into covalently crosslinked Nor-Tet hydrogels. By modifying HANor macromers with methacrylates (Me), thiolated BMP-2 …

Ethanol-Induced Impacts On Nervous System Development And Dopamine Transporter Characterization In Schmidtea Mediterranea Planaria, Brennen Covely

Theses and Dissertations

Fetal alcohol spectrum disorders (FASD) are diagnosed in 2-5% of newborns, but the biology underlying FASD is poorly understood and challenging to study with existing model organisms. A new model for FASD research is Schmidtea mediterranea (Smed) planaria. Smed have a remarkable ability to regenerate their central nervous system (CNS), and possess a well-studied, simple genome. Previous studies have shown that ethanol exposure delays this regeneration, yet this relationship is not fully understood. Here, we show that alcohol exposure affects Smed in a dose-dependent manner, eliciting characteristic withdrawal-like behaviors and impacting cognitive function. Interestingly, prior exposure does not alter subsequent …

Hyaluronic Acid: Its Versatile Use In Ocular Drug Delivery With A Specific Focus On Hyaluronic Acid-Based Polyelectrolyte Complexes., Saoirse Casey-Power, Richie Ryan, Gautam Behl, Peter Mcloughlin, Mark Byrne, Laurence Fitzhenry

Henry M. Rowan College of Engineering Departmental Research

Extensive research is currently being conducted into novel ocular drug delivery systems (ODDS) that are capable of surpassing the limitations associated with conventional intraocular anterior and posterior segment treatments. Nanoformulations, including those synthesised from the natural, hydrophilic glycosaminoglycan, hyaluronic acid (HA), have gained significant traction due to their enhanced intraocular permeation, longer retention times, high physiological stability, inherent biocompatibility, and biodegradability. However, conventional nanoformulation preparation methods often require large volumes of organic solvent, chemical cross-linkers, and surfactants, which can pose significant toxicity risks. We present a comprehensive, critical review of the use of HA in the field of ophthalmology and …

Electro-Mechanical Data Fusion For Heart Health Monitoring, Kemal Yakut

Theses and Dissertations

Heart disease is a major public health problem and one of the leading causes of death worldwide. Therefore, cardiac monitoring is of great importance for the early detection and prevention of adverse conditions. Recently, there has been extensive research interest in long-term, continuous, and non-invasive cardiac monitoring using wearable technology. Here we introduce a wearable device for monitoring heart health. This prototype consists of three sensors to monitor electrocardiogram (ECG), phonocardiogram (PCG), and seismocardiogram (SCG) signals, integrated with a microcontroller module with Bluetooth wireless connectivity. We also created a custom printed circuit board (PCB) to integrate all the sensors into …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

Human Induced Mesenchymal Stem Cells Display Increased Sensitivity To Matrix Stiffness., Kirstene A Gultian, Roshni Gandhi, Khushi Sarin, Martina Sladkova-Faure, Matthew Zimmer, Giuseppe Maria De Peppo, Sebastian Vega

Henry M. Rowan College of Engineering Departmental Research

The clinical translation of mesenchymal stem cells (MSCs) is limited by population heterogeneity and inconsistent responses to engineered signals. Specifically, the extent in which MSCs respond to mechanical cues varies significantly across MSC lines. Although induced pluripotent stem cells (iPSCs) have recently emerged as a novel cell source for creating highly homogeneous MSC (iMSC) lines, cellular mechanosensing of iMSCs on engineered materials with defined mechanics is not well understood. Here, we tested the mechanosensing properties of three human iMSC lines derived from iPSCs generated using a fully automated platform. Stiffness-driven changes in morphology were comparable between MSCs and iMSCs cultured …

Porous Scaffold-Hydrogel Composites Spatially Regulate 3d Cellular Mechanosensing., Matthew Dicerbo, Mohammed Mehdi Benmassaoud, Sebastián L Vega

Henry M. Rowan College of Engineering Departmental Research

Cells encapsulated in 3D hydrogels exhibit differences in cellular mechanosensing based on their ability to remodel their surrounding hydrogel environment. Although cells in tissue interfaces feature a range of mechanosensitive states, it is challenging to recreate this in 3D biomaterials. Human mesenchymal stem cells (MSCs) encapsulated in methacrylated gelatin (GelMe) hydrogels remodel their local hydrogel environment in a time-dependent manner, with a significant increase in cell volume and nuclear Yes-associated protein (YAP) localization between 3 and 5 days in culture. A finite element analysis model of compression showed spatial differences in hydrogel stress of compressed GelMe hydrogels, and MSC-laden GelMe …

Bio-Ionic Liquid Functionalized Hydrogels Towards Smart Tissue Regeneration, Vaishali Krishnadoss

Theses and Dissertations

A blend of scaffolds, biologically active molecules, and cells are required to assemble functional constructs to repair and regenerate damaged tissue or organ via tissue engineering. The scaffold supports cell growth and proliferation and acts as a medium for diverse cellular activities. Even though hydrogel's high-water content and flexible nature make it a pronounced applicant as a scaffold, they exhibit significant technical limitations such as the absence of cell-binding motifs, lack of oxygen, conductivity, adhesive properties, growth of cells in a 3-dimensional (3D) microenvironment. In this thesis, a novel material platform is evaluated and studied to address the concerns mentioned …

Image Processing Algorithms For Detection Of Anomalies In Orthopedic Surgery Implants, Alexander William Wiese

Theses and Dissertations

Orthopedic implant procedures for hip implants are performed on 300,000 patients annually in the United States, with 22.3 million procedures worldwide. While most such operations are successfully performed to relieve pain and restore joint function for the duration of the patient's life, advances in medicine have enabled patients to outlive the life of their implant, increasing the likelihood of implant failure. There is significant advantage to the patient, the surgeon, and the medical community in early detection of implant failures.The research work presented in this thesis demonstrates a non-invasive digital image processing technique for the automated detection of specific arthroplasty …

Annealing Post-Drawn Polycaprolactone (Pcl) Nanofibers Optimizes Crystallinity And Molecular Alignment And Enhances Mechanical Properties And Drug Release Profiles, M. D. Flamini, T. Lima, K. Corkum, N. J. Alvarez, Vincent Beachley

Henry M. Rowan College of Engineering Departmental Research

Post-drawn PCL nanofibers can be molecularly tuned to have a variety of mechanical properties and drug release profiles depending on the temperature and time of annealing, which has implications for regenerative medicine and drug delivery applications. Post-drawing polycaprolactone (PCL) nanofibers has previously been demonstrated to drastically increase their mechanical properties. Here the effects of annealing on post-drawn PCL nanofibers are characterized. It is shown that room temperature storage and in vivo temperatures increase crystallinity significantly on the order of weeks, and that high temperature annealing near melt significantly increases crystallinity and molecular orientation on the order of minutes. The kinetics …

Targeting Hif-2Α In The Tumor Microenvironment: Redefining The Role Of Hif-2Α For Solid Cancer Therapy., Leah Davis, Matthias Recktenwald, Evan Hutt, Schuyler Fuller, Madison Briggs, Arnav Goel, Nichole Daringer

Henry M. Rowan College of Engineering Departmental Research

Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous alpha subunits, HIF-1α and HIF-2α, are responsible for mediating the transcription of a multitude of critical proteins that control proliferation, angiogenic signaling, metastasis, and other oncogenic factors, both differentially and sequentially regulating the hypoxic response. Post-translational modifications of HIF play a central role in its behavior as a mediator of transcription, as well as the temporal transition from …