Engineering Commons^™

Systematic Development Of Ionizable Lipid Nanoparticles For Placental Mrna Delivery Using A Design Of Experiments Approach, Rachel E. Young, Katherine Nelson, Samuel I. Hofbauer, Tara Vijayakumar, Mohamad-Gabriel Alameh, Drew Weissman, Charalampos Papachristou, Jason P Gleghorn, Rachel S. Riley

Henry M. Rowan College of Engineering Faculty Scholarship

Ionizable lipid nanoparticles (LNPs) have gained attention as mRNA delivery platforms for vaccination against COVID-19 and for protein replacement therapies. LNPs enhance mRNA stability, circulation time, cellular uptake, and preferential delivery to specific tissues compared to mRNA with no carrier platform. However, LNPs are only in the beginning stages of development for safe and effective mRNA delivery to the placenta to treat placental dysfunction. Here, we develop LNPs that enable high levels of mRNA delivery to trophoblasts in vitro and to the placenta in vivo with no toxicity. We conducted a Design of Experiments to explore how LNP composition, including …

Molecular Separation By Using Active And Passive Microfluidic Chip Designs: A Comprehensive Review, A. Ebrahimi, K. Icoz, R. Didarian, C.-H. Shih, A. Akpek, Berivan Cecen, Sabanci A. Bal-Ozturk, K. Güleç, Y.-C.E Li, S. Shih, B. Sirma Tarim, H.C. Tekin, E. Alarçin, H. Ghorbanpoor, C. Özel, A. Eker Sarıboyacı, Guzel F. Dogan, N. Bassous, S.R. Shin, H. Avci

Henry M. Rowan College of Engineering Faculty Scholarship

Separation and identification of molecules and biomolecules such as nucleic acids, proteins, and polysaccharides from complex fluids are known to be important due to unmet needs in various applications. Generally, many different separation techniques, including chromatography, electrophoresis, and magnetophoresis, have been developed to identify the target molecules precisely. However, these techniques are expensive and time consuming. “Lab-on-a-chip” systems with low cost per device, quick analysis capabilities, and minimal sample consumption seem to be ideal candidates for separating particles, cells, blood samples, and molecules. From this perspective, different microfluidic-based techniques have been extensively developed in the past two decades to separate …

Combining Adhesive And Nonadhesive Injectable Hydrogels For Intervertebral Disc Repair In An Ovine Discectomy Model., Christopher J Panebianco, Caroline Constant, Andrea J. Vernengo, Dirk Nehrbass, Dominic Gehweiler, Tyler J Distefano, Jesse Martin, David J Alpert, Saad B Chaudhary, Andrew C Hecht, Alan C Seifert, Steven B Nicoll, Sibylle Grad, Stephan Zeiter, James C Iatridis

Henry M. Rowan College of Engineering Faculty Scholarship

BACKGROUND: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.

METHODS: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury …

Occlusive Membranes For Guided Regeneration Of Inflamed Tissue Defects., Woojin Choi, Utkarsh Mangal, Jin-Young Park, Ji-Yeong Kim, Taesuk Jun, Ju Won Jung, Moonhyun Choi, Sungwon Jung, Milae Lee, Ji-Yeong Na, Du Yeol Ryu, Jin Man Kim, Jae-Sung Kwon, Won-Gun Koh, Sangmin Lee, Patrick T J Hwang, Kee-Joon Lee, Ui-Won Jung, Jae-Kook Cha, Sung-Hwan Choi, Jinkee Hong

Henry M. Rowan College of Engineering Faculty Scholarship

Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration …

Real-Time Arrhythmia Detection Using Convolutional Neural Networks, Thong Vu, Tyler Petty, Kemal Yakut, Muhammad Usman, Wei Xue, Francis M. Haas, Robert A. Hirsh, Xinghui Zhao

Henry M. Rowan College of Engineering Faculty Scholarship

Cardiovascular diseases, such as heart attack and congestive heart failure, are the leading cause of death both in the United States and worldwide. The current medical practice for diagnosing cardiovascular diseases is not suitable for long-term, out-of-hospital use. A key to long-term monitoring is the ability to detect abnormal cardiac rhythms, i.e., arrhythmia, in real-time. Most existing studies only focus on the accuracy of arrhythmia classification, instead of runtime performance of the workflow. In this paper, we present our work on supporting real-time arrhythmic detection using convolutional neural networks, which take images of electrocardiogram (ECG) segments as input, and classify …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Advanced Processing Techniques For Electrospun Nanofibers: Investigating Annealing And Laser Zone-Drawing Effects On Material Characteristics, Matthew D. Flamini

Theses and Dissertations

Electrospun nanofibers hold potential for a wide range of commercial and scientific applications; however, their properties must be optimized through post-processing treatments to achieve optimal performance. This dissertation investigates the effects of annealing and laser zone-drawing on electrospun nanofiber properties. Annealing polycaprolactone nanofibers at 70°C results in the highest rate of crystallization and molecular alignment, impacting long-term stability and mechanical properties. A multivariate linear model incorporating crystallinity and molecular alignment predicts the material properties resulting from annealing under different conditions. Laser zone-drawing experiments reveal that polylactide fiber thinning under laser irradiation primarily occurs due to drawing rather than ablation. Steady-state …

Cell Encapsulation In Gelatin Methacryloyl Bioinks Impairs Microscale Diffusion Properties, Elvan Dogan, Christina Holshue, Anant Bhusal, Roshni Shukla, Amir K. Miri

Henry M. Rowan College of Engineering Faculty Scholarship

Light-assisted bioprinted gelatin methacryloyl (GelMA) constructs have been used for cell-laden microtissues and organoids. GelMA can be loaded by desired cells, which can regulate the biophysical properties of bioprinted constructs. We study how the degree of methacrylation (MA degree), GelMA mass concentration, and cell density change mass transport properties. We introduce a fluorescent-microscopy-based method of biotransport testing with improved sensitivity compared to the traditional particle tracking methods. The diffusion capacity of GelMA with a higher MA significantly decreased compared to a lower MA. Opposed to a steady range of linear elastic moduli, the diffusion coefficient in GelMA varied when cell …

Efficient Scopeformer: Toward Scalable And Rich Feature Extraction For Intracranial Hemorrhage Detection, Yassine Barhoumi, Nidhal Carla Bouaynaya, Ghulam Rasool

Henry M. Rowan College of Engineering Faculty Scholarship

The quality and richness of feature maps extracted by convolution neural networks (CNNs) and vision Transformers (ViTs) directly relate to the robust model performance. In medical computer vision, these information-rich features are crucial for detecting rare cases within large datasets. This work presents the “Scopeformer,” a novel multi-CNN-ViT model for intracranial hemorrhage classification in computed tomography (CT) images. The Scopeformer architecture is scalable and modular, which allows utilizing various CNN architectures as the backbone with diversified output features and pre-training strategies. We propose effective feature projection methods to reduce redundancies among CNN-generated features and to control the input size of …

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 Faculty Scholarship

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 Faculty Scholarship

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-Öztürk, Ece Özcan-Bülbül, Hazal Ezgi Gültekin, Berivan Cecen, Ebru Demir, Atefeh Zarepout, Sibel Cetinel, Ali Zarrabi

Henry M. Rowan College of Engineering Faculty Scholarship

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 …

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

Henry M. Rowan College of Engineering Faculty Scholarship

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 …

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 …