Engineering Commons^™

Oxidized Fibrin Alginate Microbeads To Treat Vascular Calcification, Brittany Nichole Macha

Theses and Dissertations

Calcification is linked to a high prevalence of cardiovascular events and mortality due to arterial stiffness. Stiffening of the arteries in the case of medial calcification is due to hydroxyapatite mineral deposited in the artery thus leading to the loss of elastin. A possibility of removing this rogue mineral along the vessel walls could be the use of osteoclasts. Osteoclasts, a type of osteocyte, have the unique ability to absorb bone in the bone turnover process. It is proposed that in the future, osteoclasts be delivered to the site of mineralization through oxidized alginate-fibrin microbeads. Alginate hydrogels have proven great …

Pulsatility Is A Predictive Marker Of Improved Cardiac Function In Patients With Liquid Matrix-Treated Left Ventricular Assist Devices, Philemon Mikail, Rinku Skaria, Marvin Slepian, Janny Garcia, Richard Smith, Zain Khalpey

The VAD Journal

Objective: Left ventricular assist devices (LVADs) are utilized as a bridge to transplant or as destination therapy for patients with end-stage heart failure. Although cardiac offloading from these devices rarely leads to complete remodeling and functional recovery, the use of mesenchymal cells to modulate heart failure has been explored in recent years due to its intrinsic regenerative properties. Current methods of evaluating cardiac function have too much variability, difficulty of access, or require too frequent follow up to create universal weaning protocols. We hypothesized that the administration of amniotic allograft liquid matrix (LM) containing amnion-derived mesenchymal stem cells (aMSCs) in …

Acoustofluidic Delivery Of Gene Editing Compounds For Improved Immunotherapy Processing., Riyakumari K. Patel

Electronic Theses and Dissertations

Cell-based immunotherapies are a new generation of “living-drug” treatments for cancer and other diseases. Chimeric antigen receptor (CAR) T-cell cancer therapy has shown promising results in lymphoma and B-cell malignancies. Currently, there are six FDA-approved CAR-T drugs on the market, and all of them use viral transfection for reprogramming. While viral transfection is effective, there are safety concerns due to inconsistent transfection that limit the use of CAR-T therapy. Current non-viral transfection techniques generally have lower transfection efficiency than viral transfection. Additionally, these techniques can be toxic, time-consuming, non-transportable, and expensive. To address these limitations, a novel 3D printed acoustofluidic …

Cfd Analysis Of Acoustofluidic Channels And The Effects On Biologic Delivery., Zachary T. Long

Electronic Theses and Dissertations

T-cell transformation is an ever-expanding treatment for several types of cancer, with a potential to be adapted to other disorders in which the immune system plays a key role in the pathophysiology. Currently, all FDA approved chimeric antigen receptor (CAR) T-cell cancer therapies rely on transformation via viral transduction. However, viral transduction is plagued by poor consistency and the potential to create adverse immune reactions when T-cells are reintroduced into a patient. Other transformation methods are being explored, with an alternative called acoustofluidic sonoporation showing promise. In these procedures, cells are passed through a channel, of the millimeter scale, while …

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …

Isolation And Culture Of Myofiber-Derived Cells From The Extensor Digitorum Longus Muscle, Ethan M. Tietze

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) involves distal artery occlusion by atherosclerotic plaques, which restricts blood flow and leads to ischemia in downstream tissues. Increased blood flow through preexisting collateral vessels leads to increased shear stress that triggers an outward remodeling of the vessel called arteriogenesis. In some cases this natural compensatory mechanism is able to sufficiently restore blood flow following arterial occlusion. However, for many individuals this process is insufficient to relieve peripheral ischemia, and patients experience intermittent claudication, or limb pain with locomotion or exercise. Without treatment, reduced blood flow can lead to tissue necrosis and potentially amputation. The …

Optimization Of A Defined Serum-Free Medium For The Production Of Therapeutic Human Myoblasts, Alain Garnier

Cell Culture Engineering XV

Duchenne Muscular Dystrophy (DMD) is a genetic disease affecting one boy out of 3500, which is due to a mutation in the dystrophin gene, inducing progressive and irreversible muscle degeneration. Cell therapy is the only means by which a DMD patient could recover part of his muscular mass and strength. We are presently collaborating with a team at the Quebec City University Hospital who is developing a cell therapy based on the graft to DMD patients of myoblasts obtained from biopsies on healthy and compatible donors. To do so, cells collected from donors need to be extensively multiplied. The standard …

Exploring Continuous And Integrated Strategies For The Up- And Downstream Processing Of Human Mesenchymal Stem Cells, Barbara Cunha, Tiago Aguiar, Ricardo Silva, Cristina Peixoto, Manuel Carrondo, Margarida Serra, Paula Alves

Integrated Continuous Biomanufacturing II

The integration of up- and downstream unit operations can result in the elimination of hold steps, thus decreasing the footprint, and ultimately can create robust closed system operations. This type of design is desirable for the bioprocess of human mesenchymal stem cells (hMSC), where high numbers of pure cells, at low volumes, need to be delivered for therapy applications. The aim of this work is to perform a proof of concept of the integration of a continuous perfusion culture in bioreactors with a tangential flow filtration (TFF) system for the concentration and washing of hMSC. In particular, we have evaluated …

Fluid Flow-Induced Mesenchymal Stem Cell Migration: Role Of Fak And Rock Mechanosensors, Brandon D. Riehl

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

The study of mesenchymal stem cell (MSC) migration under mechanical stimulation conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcomes in stem cell-based regenerative medicine. MSCs having multipotent regenerative capability exist in niches in the bone marrow, muscle, vasculature, and in other tissues throughout the body, and their migration through tissues and vasculature for the repair of damaged tissue is a key process of cell and tissue homeostasis, remodeling, and regeneration. While cell migration in response to cytokines and other chemo-attractants is relatively well understood, little is revealed in regard to the effect …

Slowing The Onset Of Hypoxia Increases Colony Forming Efficiency Of Connective Tissue Progenitor Cells In Vitro, Christopher M. Heylman, Tonya N. Caralla, Cynthia A. Boehm, Thomas E. Patterson, George F. Muschler

Biomedical Engineering

Background: Survival and colony formation by transplanted tissue derived connective tissue progenitor cells (CTPs) are thought to be important factors in the success of clinical tissue engineering strategies for bone regeneration. Transplantation of cells into defects larger than a few millimeters expose cells to a profoundly hypoxic environment. This study tested the hypothesis that delaying the onset of hypoxia will improve the survival and performance of CTPs in vitro.

Methods: To mimic declines seen in an avascular in vivo bone defect, colony forming efficiency by marrow derived nucleated cells was assessed under osteogenic conditions. Variation in the rate of …