Biomedical Engineering and Bioengineering Commons^™

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 Faculty Scholarship

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 …

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 Faculty Scholarship

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 Faculty Scholarship

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 …

Mechanotransductive Feedback Control Of Endothelial Cell Motility And Vascular Morphogenesis, Devon E. Mason, Megan Goeckel, Sebastian Vega, Pei-Hsun Wu, Dymonn Johnson, Su-Jin Heo, Denis Wirtz, Jason A. Burdick, Levi Wood, Brian Y. Chow, Amber N. Stratman, Joel D. Boerckel

Henry M. Rowan College of Engineering Faculty Scholarship

Vascular morphogenesis requires persistent endothelial cell motility that is responsive to diverse and dynamic mechanical stimuli. Here, we interrogated the mechanotransductive feedback dynamics that govern endothelial cell motility and vascular morphogenesis. We show that the transcriptional regulators, YAP and TAZ, are activated by mechanical cues to transcriptionally limit cytoskeletal and focal adhesion maturation, forming a conserved mechanotransductive feedback loop that mediates human endothelial cell motility in vitro and zebrafish intersegmental vessel (ISV) morphogenesis in vivo. This feedback loop closes in 4 hours, achieving cytoskeletal equilibrium in 8 hours. Feedback loop inhibition arrested endothelial cell migration in vitro and ISV morphogenesis …