Molecular, Cellular, and Tissue Engineering Commons^™

Characterization Of Molecular Communication Based On Cell Metabolism Through Mutual Information And Flux Balance Analysis, Zahmeeth Sayed Sakkaff

School of Computing: Dissertations, Theses, and Student Research

Synthetic biology is providing novel tools to engineer cells and access the basis of their molecular information processing, including their communication channels based on chemical reactions and molecule exchange. Molecular communication is a discipline in communication engineering that studies these types of communications and ways to exploit them for novel purposes, such as the development of ubiquitous and heterogeneous communication networks to interconnect biological cells with nano and biotechnology-enabled devices, i.e., the Internet of Bio-Nano Things. One major problem in realizing these goals stands in the development of reliable techniques to control the engineered cells and their behavior from the …

Ionic Basis Of Ventricular Action Potentials, Ariel L. Escobar

Science Seminar Series

Dr. Escobar will talk about his cutting-edge approach to understanding molecular mechanisms underlying electrical activity in the heart.

Alginate Hydrogels As Three-Dimensional Scaffolds For In Vitro Culture Models Of Growth Plate Cartilage Development And Porcine Embryo Elongation, Taylor D. Laughlin

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

The establishment of in vitro culture models utilizes tissue engineering principles to design functional mimics of in vivo environments in vitro. Advantages for the use of in vitro culture models include ethical alleviation of animal models for therapeutic testing, cost efficiency, and a greater ability to study specific mechanisms via a systematic, ground-up approach to development. In this thesis, alginate hydrogels are utilized in the development of in vitro culture models of porcine embryo elongation and growth plate cartilage development. First, the effect of scaffold and modifications to the scaffold were explored in both projects. In order to modulate …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Hyaluronic Acid-Conjugated Liposome Nanoparticles For Targeted Delivery To Cd44 Overexpressing Glioblastoma Cells, Stephen L. Hayward, Christina L. Wilson, Srivatsan Kidambi

Department of Chemical and Biomolecular Engineering: Faculty Publications

Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

A Collagen Based Tissue Engineered Heart Valve Shows Excellent Functionality And Remodelling After Dynamic Conditioning, Claire Brougham, Ricardo Moreira, Tanya J. Levingstone, Stefan Jockenhoevel, Petra Mela, Fergal J. O'Brien

Conference Papers

No abstract provided.

Bioengineered Cell Niche For Skeletal Muscle Regeneration, Nicole M. Whittern, Naagarajan Narayanan, Chunhui Jiang, Owen Jones, Jay Gilbert, Michael Whittern, Shihuan Kuang, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Skeletal muscles can self-repair minor strains, lacerations, and contusions; however, in cases of volumetric muscle lossand muscle degenerative diseases, tissue fails to regenerate. Current cell-based therapies, such as myoblast transplantation, have significant drawbacks of low survival rates and engraftment efficacy, mainly due to the absence of supportive cell microenvironment. Scaffolds that mimic the natural cell microenvironment provide a robust platform to support cell adhesion, migration, proliferation, and differentiation. Electrospinning is a versatile technology platform used for fabricating the fiber scaffold that mimics the extracellular matrix. Thus, we aim to reconstitute the cell microenvironment through development of aligned fiber scaffolds by …

Proteoglycan Mimic Of The Glycocalyx To Treat Endothelial Dysfunction, Victoria Messerschmidt, Alyssa Panitch, James R. Wodicka

The Summer Undergraduate Research Fellowship (SURF) Symposium

Patients with kidney failure usually undergo hemodialysis, a process by which toxins produced by the body are filtered from the blood, in order to survive. The preferred form for vascular access is called an arteriovenousfistula (AVF), a surgically created connection between an artery and vein that is utilized to undergo dialysis. However, AVFs have a failure rate of 50-60%. One of the contributions to AVF failure is endothelial cell dysfunction and loss of glycocalyx, which allows neutrophils and other native cells into the media of the vessel, which causes an inflammatory response. Our lab addresses endothelial dysfunction by mimicking the …

Harnessing Notch Signaling For Biomaterial Scaffold-Based Bone Regeneration, Helena P. Lysandrou, Chunhui Jiang, Naagarajan Narayanan, Shihuan Kuang, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Bone fracture has recently become prevalent, especially with an increasingly aging population. Current bone grafts procedures, including autografts and allografts, are hindered by multiple factors, such as limited supplies and inconsistent bone healing. Scaffold-based bone tissue engineering emerges as a prospective strategy to aid in bone regeneration through delivery of growth factors such as bone morphogenic proteins (BMPs). However, the use of BMPs suffers from several drawbacks such as protein instability and immunogenicity. Therefore, there exists a great need for the development of novel therapies to promote bone healing. Notch signaling, a pathway critical for cell-fate determination has been shown …

Breast Cancer/Stromal Cells Coculture On Polyelectrolyte Films Emulates Tumor Stages And Mirna Profiles Of Clinical Samples, Amita Daverey, Karleen M. Brown, Srivatsan Kidambi

Department of Chemical and Biomolecular Engineering: Faculty Publications

In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell−cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes …

Capillary Electrophoresis For Analysis Of Aβ1-42 Adsorption And Photo-Crosslinking, Jennifer Lynn Kurtz

Graduate Theses and Dissertations

The accumulation of amyloid-beta (Aβ) oligomers is believed to be the driving force behind Alzheimer’s disease (AD) pathogenesis. Due to the metastable nature of Aβ oligomers, the knowledge of Aβ aggregation and accumulation is not well understood. Here, we use capillary electrophoresis (CE) and photo-induced crosslinking of unmodified proteins (PICUP) to learn about the aggregation of Aβ.

First, we explore the effect of capillary coating on Aβ1-42 protein loss using CE. The dynamic coatings tested were PHEA and 50 kDa, 2000 kDa, 5000 kDa, and 8000 kDa PEO. The covalent coating tested was PVA. The results indicated that 2000 kDa …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations and Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

Systematic Study Of The Biological Effects Of Nitric Oxide (No) Using Innovative No Measurement And Delivery Systems, Weilue He

Dissertations, Master's Theses and Master's Reports

Nitric oxide (NO) is recognized as the most important small signaling molecule in the human body. An imbalance of NO is closely associated with many serious diseases such as neurological disorders, cardiovascular diseases, chronic inflammations and cancers. Herein two chemiluminescence-based devices (a real-time NO measurement device and a controllable NO delivery device) were developed to facilitate the NO quantitative study and obtain information for NO related drug design.

The first device used for real-time measuring NO(g) flux from living cells was developed and validated. The principle was to use a two-chamber design, with a cell culture chamber and a gaseous …

Up Regulation Of Heat Shock Protein 70b (Hsp70b) And Ssa1 In Chlamydomonas Reinhardtii Via Hsp70a-Rbcs2 And Psad Promoter, B. Kirtley Amos

Theses and Dissertations--Biosystems and Agricultural Engineering

Fabrication of effective algae cultivation systems adjacent to coal-fired power plants to fixate waste CO₂ would represent a sizable step towards achieving a carbon neutral energy cycle. However, emission gas would elevate the algal cultivation system temperature and decreases its pH without expensive preprocessing. Increased temperature and acidity constitutes a profound stress on the algae. Although stressed algae produce heat shock proteins (HSPs) that promote protein folding and protect against stress, the ordinary biological response is insufficient to protect against coal flue gas. Experimental upregulation of HSPs could make algae respond to the stress caused by high temperatures and …

Ex Vivo Dna Cloning, Adam B. Fisher

Theses and Dissertations

Genetic engineering of microbes has developed rapidly along with our ability to synthesize DNA de novo. Yet, even with decreasing DNA synthesis costs there remains a need for inexpensive, rapid and reliable methods for assembling synthetic DNA into larger constructs or combinatorial libraries. While technological advances have resulted in powerful techniques for in vitro and in vivo assembly of DNA, each suffers inherent disadvantages. Here, an ex vivo DNA cloning suite using crude cellular lysates derived from E. coli is demonstrated to amplify and assemble DNA containing small sequence homologies. Further, the advantages of an ex vivo approach are …

Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale

Theses and Dissertations

Although researchers have been able to print small, simple, and avascular tissues, they have been unsuccessful in creating large, complex and vascularized organs. Printing large and complex three-dimensional tissues or organs involves utilizing a large quantity of cellular spheroids and layer-by-layer addition of spheroids. In this study, an in-house cell spheroid fabrication system was developed to produce cell spheroids with human liver cells (hepG2), human endothelial cells (hEC), human neural stem cells (hNSC), and induced pluripotent stem cells (iPSC). It offers the ability of fabricating uniform-sized spheroids repeatedly, which is essential when large and complex structures need to be produced. …

Developing Defined And Scalable 3d Culture Systems For Culturing Human Pluripotent Stem Cells At High Densities, Yuguo Lei, Daeun Jeong, Jifang Xiao, David V. Schaffer

Department of Chemical and Biomolecular Engineering: Faculty Publications

Human pluripotent stem cells (hPSCs)—including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)—are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation. Here, we describe additional design rationale and characterization of this …

Application Of Limited Mixing In The Hele–Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

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

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Evaluation Of Tissue-Engineered Tendon Enthesis Polymer Constructs, Joshua A. Bundy Bs, Mary Beth Wade Phd, Hitomi Nakao Md, Phillip Mcclellan Phd, Qing Yu Phd, Robin Jacquet-Childs Ms, William J. Landis Phd

Williams Honors College, Honors Research Projects

Both scientists and clinicians have proposed tissue engineering as the future of medicine. The possibilities for tissue engineering, that is, fabrication of tissues and organs in the laboratory and their translation to patients, appear to be endless, and many believe that this new approach in medicine will result in abolishing many common ailments, injuries, and congenital defects. Injuries to a tendon enthesis, the normal tissue connection between tendon and bone, are of particular concern to clinicians because of their frequency and failure to repair as a result of surgery. While these injuries may not be life threatening, they can certainly …

Adhesive Elastomeric Proteins, Haefa Mansour, Julie Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Sutures and staples commonly used to close surgical wounds tend to be much stiffer than the surrounding tissue, often resulting in external tissue damage. Surgical adhesives provide a promising alternative to these sutures and staples. Ideal surgical adhesives are biocompatible, able to set well and remain sticky in moist conditions, possess strong adhesive and cohesive properties, and exhibit mechanical properties that mimic those of the surrounding tissue. Unfortunately, the adhesives available today are unable to satisfactorily meet all of these criteria. We are utilizing protein engineering techniques to design, create, and test a new surgical adhesive that combines the adhesive …

Zein: Novel Natural Polymer For Nanoparticle- And Film-Mediated Gene Delivery, Jessica D. Taylor

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Gene delivery, the introduction of DNA into cells, is applicable to gene therapy, DNA vaccination, functional genomics and diagnostics, tissue engineering, and drug-eluting medical devices. Particulates incorporating DNA are promising vehicles for gene delivery and overcome some of the barriers that hinder successful gene transfer, with the ability to protect DNA and provide for controlled, localized, and sustained release and transfection. Furthermore, innovative new gene delivery strategies that incorporate DNA particulates or complexes within films or coatings for devices and scaffolds could further provide for controlled and sustained transfection at the site of implant. Zein, a hydrophobic protein from corn, …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

Surface- And Hydrogel-Mediated Delivery Of Nucleic Acid Nanoparticles, Angela K. Pannier, Tatiana Segura

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. …

Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover

Biomedical Engineering

Numerous molecular factors active in bone tissue direct fracture repair and remodeling which can be altered by disease conditions such as Peripheral Arterial Disease (PAD) and Osteoporosis. Methods of molecular biology are commonly applied to investigate the expression and role of these molecular factors. This project presents a robust three-step protocol for examining gene expression in the mouse tibia. The protocol begins with isolating RNA from a flash frozen tibia sample. The isolated RNA is reverse transcribed into cDNA. Finally, PCR is performed to indentify expressed genes. Establishing this protocol will allow further research into the mechanisms of bone remodeling …

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

IP Theory

No abstract provided.

Effect Of Extracellular Matrix (Ecm) Protein Micropatterns On The Behavior Of Human Neuroblastoma Cells, Ishwari Poudel

Department of Engineering Mechanics: Dissertations, Theses, and Student Research

Recent advances in patterning techniques and emerging surface microtechnologies have allowed cell micropatterning to control spatial location of the cells on a surface as well as cell shape, attachment area, and number of contacting neighbor cells. These parameters play important roles in cell cellular behaviors. Cell micropatterning has thus become one of the most important strategies for biomedical applications, such as, tissue engineering, diagnostic immunoassays, lab-on-chip devices, bio-sensing, etc., and cell biology studies as well. For neuronal cells, there have been attempts to distribute neuronal cells on specific patterns to control cell-to-cell interaction. However, there have been very limited understanding …

Protective Effects Of Milk Phospholipids Against Uv Photodamage In Human Skin Equivalents, Zyra Achay

Master's Theses

The ultraviolet (UV) spectrum has been known to cause damage to skin in varying degrees. UVB radiation (290-320 nm) in particular, has been proven to be highly mutagenic and carcinogenic in many animal experiments compared to either UVA or UVC. The alarming rate of increase in skin cancer incidence has prompted many investigators to pursue other alternatives to sunscreens including changes in lifestyle habits and dietary consumption in order to boost our efforts in tackling this widespread disease. Previous studies employing confocal reflectance, MTT assay and histology suggest that milk phospholipids may possess protective properties against UVB-mediated damage but the …

Development Of An In-Vitro Hyperglycemic Tissue Engineered Blood Vessel Mimic, Brian C. Wong

Biomedical Engineering

No abstract provided.