Molecular, Cellular, and Tissue Engineering Commons^™

Reporter Chondrocyte Optimization Of Bioinks For Zonal 3d Bioprinting Of Cartilage, Kari Martyniak

Electronic Theses and Dissertations, 2020-2023

Osteoarthritis (OA) is the most common form of arthritis, often thought of as a disease of the elderly, but post traumatic OA predominantly impacts younger individuals. Articular cartilage is the tissue that coats the end of your bones in synovial joints. Since cartilage has limited healing capacity, defects, or injuries to it progressively erodes down to the subchondral bone. Unfortunately, current treatment options all have limitations, particularly for younger patients. Cartilage has a specific zonal architecture that is distinguished by the different cell morphologies and arrangements, biochemical composition, and mechanical properties. 3D bioprinting is a tissue engineering technique that involves …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Dna Condensation State Regulates Nuclear Lamina Strain And Cellular Adaptation To Physiological Forces, Brooke E. Danielsson

Theses and Dissertations

The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell, as well as from forces generation within the cell. In recent years, the nucleus has been proposed to act as a cellular mechanosensor, with changes to nuclear shape and architecture playing an important role in how the cell responds to physiological forces. Aberrant forms of the nuclear envelope protein lamin A/C, as well as epigenetic modifications to chromatin, has been shown to modify nuclear stiffness and viscosity, therefore effecting nuclear mechanics and mechanotransduction. Altered nuclear mechanics is associated …

Modulation Of Brain Tissue Transport And Endothelial Glycocalyx And Tight Junctions Of The Blood-Brain Barrier By Transcranial Direct Current Stimulation, Yifan Xia

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive approach to treat a broad range of brain disorders and to enhance memory and cognition in healthy individuals. In addition to directly acting on neurons by modulating the membrane potential, inducing neuronal polarization and changing cortical excitability in the brain to achieve its therapeutic effects, prior studies found that tDCS can transiently enhance the permeability (P) of the blood-brain barrier (BBB), the interface between blood circulation and brain tissue. Brain extracellular space (ECS) is a narrow microenvironment which surrounds every cell in the central nervous system (CNS). ECS occupies ~20% of brain …

Towards The Systematic Evaluation Of Variable Modes Of Mechanical Conditioning On The Compositional, Microstructural And Mechanical Properties Of Engineered Tissue Vascular Grafts., Sarah Saunders

Theses and Dissertations

Coronary artery bypass surgery (CABG) remains one of the most common cardiac surgical procedures performed worldwide, frequently involving multiple bypasses, and commonly employing the patient’s internal mammary artery, radial artery, or saphenous vein. CABG is often not possible because native vessels were already employed in previous interventions or are diseased themselves. Synthetic vascular grafts are currently integral tools of vascular surgery and have had relative success in large-caliber applications providing substantial benefit to aortic or iliac grafting; however, small diameter (< 6 mm) arterial grafts have not yet translated into clinical effectiveness due to thrombosis and anastomotic intimal hyperplasia. ETVGs present an exciting potential alternative in vascular grafting by offering a blood vessel substitute that could exhibit all the functional characteristics of native vasculature. In addition to relieving supply limitations associated with coronary artery bypass surgery ETVGs are especially ideal for pediatric patients with congenital heart disease who require grafts that grow as they do, eliminating the need for reoccurring invasive surgeries.

Though the role of biomechanics in regulating cellular behavior promoting non-thrombogenicity, vasoactivity, and ECM synthesis and maintenance is well …

Effect Of Viscoelasticity On Cellular Morphology And Activity, Thomas J. Petet Jr

Theses and Dissertations

It has been well established that there is a link between substrate stiffness and cellular activities such as proliferation, migration, and differentiation. Less characterized is the link between the time-dependent viscosity of a substrate with those cellular activities. To explore this, PDMS substrates were created with predictably tunable stiffness and viscosity parameters. A simulated model was also developed in parallel to explore the potential effects of viscosity in a computationally predictive way. It was found that the inclusion of viscosity caused a major paradigm shift to a non-zero substrate equilibrium that was sensitive to increases in the substrate stiffness. Finally, …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

The Role Of Pro-Longevity Micrornas In Aging, Sarah Noureddine

Electronic Theses and Dissertations, 2020-2023

Cellular senescence, a hallmark of aging, has been implicated in the pathogenesis of many major age-related disorders, including atherosclerosis, metabolic disease, and neurodegenerative disorders such as Alzheimer's disease (AD). AD is characterized by increased cognitive impairment and treatment options available provide minimal disease attenuation. Additionally, diagnostic methods for AD are not conclusive with definitive diagnoses requiring postmortem brain evaluations. Therefore, miRNAs, a class of small, non-coding RNAs, have garnered attention for their ability to regulate a variety of mRNAs and their potential to serve as both therapeutic targets and biomarkers of disease. Several miRNAs have already been implicated with AD …

Exploring Cell Differentiation Vs. Localization In Engineered Ligament-To-Bone Entheses, Saagar N. Sheth, Michael E. Brown, Jennifer L. Puetzer

UROP Posters

The anterior cruciate ligament (ACL) connects to bone via structurally complex insertions known as entheses that translate load from elastic ligament and stiff bone via gradients in organization, composition, and cell phenotype [1]. These gradients are not recreated in graft repair or engineered replacements, yielding limited repair options and high failure rates [2]. Previously, we developed a culture system that uses a tensile-compressive interface to guide ligament fibroblasts to develop early postnatal-like entheses by 6 weeks [3]; however, cells used were isolated from the entirety of the neonatal bovine ACL from bone to bone and likely contained multiple cell phenotypes …

Multimodal Ultrasound Imaging For Improved Metastatic Lymph Node Detection, Sidhartha Jandhyala

Dartmouth College Ph.D Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is complex in nature due to the variety of organs located in the head and neck region. Knowing the metastatic state of the lymph nodes is paramount in accurately staging and treating HNSCC patients. Currently, metastatic lymph node detection involves the use of magnetic resonance imaging and/or x-ray computed tomography, followed by biopsies for histological confirmation. The main diagnostic criteria is the size of the nodes; however, current imaging methods are not 100% accurate due natural lymph node variability. Ultrasound imaging is able to provide …