Molecular, Cellular, and Tissue Engineering Commons^™

Stentrx, Emma Barna, Minuthi Cooray, Bruce Newlands, Joseph A. Sabetta

Williams Honors College, Honors Research Projects

This project aims to develop a biodegradable, drug-eluting biliary stent for the treatment of biliary cancers. Current metal stents that restore bile flow bit are non-degradable, prone to migration, and unable to deliver drugs locally. The proposed stent will be biocompatible, biodegradable, and capable of controlled drug release to both maintain bile flow and treat tumors. The end goal is to produce a functional prototype that can be deployed via a minimally invasive catheter and maintain bile duct patency for at least three months. The project is expected to be involved in the NEOMED Bench-to-Bedside competition and provisionally patented.

Generation And Characterization Of Human Blood-Brain Barrier Models For Investigating Neuropsychiatric Disorders And Tumor Metastasis, Yunfei Li

Dissertations and Theses

The blood–brain barrier (BBB) is important in the normal function of the central nervous system (CNS). An altered BBB has been described in various neuropsychiatric disorders. The brain-specific microvascular endothelial cell (BMEC) is an essential structural component of the BBB. To test if integrity of the BBB formed by BMECs is compromised in 22q11.2 deletion syndrome (also called DiGeorge syndrome), which is one of the validated genetic risk factors for schizophrenia, a 2D iBBB (induced BBB) on a Transwell filter was generated from human microvascular endothelial cells (HBMECs) derived from the induced pluripotent stem cells (iPSCs) out of patients with …

Engineering An Injectable Hydrogel With Self-Assembling 3d Vasculature, Kendyl Cohn

Master's Theses

This research developed methods for culturing self-assembling capillaries in an injectable gel as a potential method for vascularizing tissue-on-a-chip models to mimic physiological drug delivery. Additionally, a mathematical model was developed as a tool for understanding nutrient delivery and comparison of potential delivery systems. Organs-on-a-chip provide novel platforms for studying biology and physiology in 3D, allow exploration of tissue engineering on a manageable scale, and serve as models for drug screening and drug-delivery testing.

Methods were first developed for co-culture of endothelial cells and fibroblasts (3T3s or HDFs) in 2D, evaluating culture time, seeding density and ratio of HUVECs and …

Investigating Endothelial Damage During Ischemic Stroke Treatment Using In Vitro And Computational Models, Zackary Lorton

Theses and Dissertations

Large vessel occlusion during acute ischemic strokes requires mechanical thrombectomy (MT) procedures using stent retrievers (SR). However, complete clot removal typically takes several attempts, which can amplify endothelial cell injury (EI). This project aims to characterize the extent of EI during MT using an in vitro vascular platform and a finite-element model (FEM). Impact of SR diameter and characterization of SR mechanical forces are assessed and correlated with human umbilical vein endothelial cell (HUVEC) response. HUVECs were seeded on fibronectin (4 µg/cm²) coated true-scale PDMS arterial phantoms with 2.5 mm luminal diameter. Test groups (n=6) either …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

Matrix Stiffness Sensing By Nascent Adhesions And The Role Of Riam In Adhesion Assembly, Nikhil Mittal

Dissertations, Master's Theses and Master's Reports

Mechanical stiffness of the extracellular matrix (ECM) impacts many cellular functions such as proliferation, migration, and differentiation. ECM stiffness is sensed by a cell via integrin-based focal adhesions (FAs) by changing conformation and biochemical activities of molecules within FAs by the exchange of the force between the ECM and filamentous actin (F-actin). Cells in turn respond to this stiffness by generating traction force that plays an important role in many biological events such as tissue morphogenesis, stem cell differentiation, wound healing, and cancer cell metastasis. The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. Understanding stiffness sensing …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Computational Modeling Using A Novel Continuum Approach Coupled With Pathway-Informed Neural Networks To Optimize Dynein-Mediated Centrosome Positioning In Polarized Cells, Arkaprovo Ghosal, Padmanabhan Seshaiyar Dr., Adriana Dawes Dr., General Genomics Inc.

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Guar-Based Injectable Hydrogel For Drug Delivery And In Vitro Bone Cell Growth, Humandra Poudel, Ambar R. Rangumagar, Pooja Singh, Adeolu Oluremi, Nawab Ali, Fumiya Watanabe, Joseph Batta-Mpouma, Jin-Woo Kim, Ahona Ghosh, Anindya Ghosh

Chemistry & Biochemistry Faculty Publications and Presentations

Injectable hydrogels offer numerous advantages in various areas, which include tissue engineering and drug delivery because of their unique properties such as tunability, excellent carrier properties, and biocompatibility. These hydrogels can be administered with minimal invasiveness. In this study, we synthesized an injectable hydrogel by rehydrating lyophilized mixtures of guar adamantane (Guar-ADI) and poly-β-cyclodextrin (p-βCD) in a solution of phosphate-buffered saline (PBS) maintained at pH 7.4. The hydrogel was formed via host-guest interaction between modified guar (Guar-ADI), obtained by reacting guar gum with 1-adamantyl isocyanate (ADI) and p-βCD. Comprehensive characterization of all synthesized materials, including the hydrogel, was performed using …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

All Dissertations

Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

Novel Microfluidic Devices To Model The Interactions Between Lymphatics And Breast Cancer, Jade Weber

McKelvey School of Engineering Graduate Student Theses & Dissertations

The lymphatic system is responsible for immune circulation and fluid balance in the body. It accomplishes this by draining interstitial fluid from local tissue and transferring it to lymph nodes and back into blood circulation. However, this process is implicated in many pathologies, one of the most dangerous being breast cancer metastasis to the lymph nodes. The largest factor in breast cancer patient mortality is metastasis. Lymphangiogenesis, the growth of new lymphatic vessels, has been thought to play a dynamic role in aiding breast cancer metastasis. Breast cancer tumor cells have been shown to remodel the functionality of local lymph …

A Magneto-Rheological Platform To Dynamically Control Afterload In Engineered Micro Heart Muscles, David Schuftan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiovascular disease is the leading cause of death is the United States, accounting for nearly 1 in 5 deaths. Many types of cardiovascular disease are linked to the mechanical forces placed on the heart. However, how these mechanical forces exactly affect the cellular biology of the heart is not well defined. In vitro models using cardiomyocytes derived from human induced pluripotent stem cells enable researchers to develop medium throughput systems to study cardiac mechanobiology at the cellular level. Previous models have been developed to enable the study of mechanical forces such as cardiac afterload. However, most of these models require …

Dpd Guided Insight On The Formation Process Of Polyethersulfone Membranes By Nonsolvent Induced Phase Separation And The Effects Of Additives, Eric Ledieu

Graduate Theses and Dissertations

Dissipative particle dynamics (DPD), a coarse grain simulation method, was applied to the membrane formation process of non-solvent induced phase separation (NIPS) to gain further insight on the mechanism of certain variables and how they affect the final morphology. NIPS involves two solutions, an organic polymer dissolved in an organic solvent colloquially called the dope and an aqueous coagulation bath, brought into contact with one another. The solvents then mix, causing the polymer to fall out of solution as an asymmetric membrane with a dense surface layer and a more open subsurface layer in response to the decreasing solubility. Polyethersulfone …

Effect Of Human Decellularized Skeletal Muscle On Recovery From Volumetric Muscle Loss Injury, Jacob Schluns

Graduate Theses and Dissertations

Volumetric muscle loss (VML) overwhelms muscle’s robust capacity for regeneration. A key event in the etiology of VML injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). While muscle is a highly structured tissue, with cell and ECM alignment in the direction of contractile force production, the impact of scaffold alignment on recovery remains unclear. Bulk human decellularized skeletal muscle (DSM) tissues were sectioned into 10 x 1-2 mm fibers. VML defects were repaired using multi-fiber implants consisting of approximately 8 fibers per defect arranged into two layers. Fibers were oriented 1) to the …

Polymeric Biomaterials Approaches For Engineering The In Vitro Cellular Microenvironment For Mscs, Mahsa Letter-Mahsa Haseli

Graduate Theses and Dissertations

Cell therapy is a technology that relies on replacing diseased or dysfunctional cells with healthy functioning ones. One of the cells used for such advanced therapies are stem cells, owing to their ability to differentiate into specific cells required for repairing damaged or defective tissues or cells. The majority of cell-based products are intended to transiently persist in the patient, secreting factors which then allow the patient’s body to heal; in these products, the cells are subsequently eliminated from the body. Furthermore, unique manufacturing platforms, in addition to novel commercialization strategies, will be required to create a successful, sustainable cell …

Histological Evidence For The Therapeutic Effect Of Chitosan Nanofibrous Dressing On Acute Skin Wounds In A Rat Model, Mahboubeh Ghanbari, Sayed Ahmadreza Razian, Sara Cartwright, Yury Salkovskiy, Jason Mactaggart, Mark A. Carlson

UNO Student Research and Creative Activity Fair

Introduction: Large-area skin traumas, such as thermal burns, are among the most severe health issues that decrease patients’ quality of life and burden healthcare systems. The CDC estimates that there are 1.1 million burns requiring medical attention each year, with more than 20,000 cases involving at least 25% of the body surface, resulting in 4,500 deaths. In addition, about 10,000 people die from burn-related infections. A promising solution to alleviate this problem is using wound dressings based on biopolymers with inherent wound healing properties and biodegradability. One of these biopolymers is chitosan, which is derived from arthropod shells and exhibits …

The Effects Of Demographics And Risk Factors On The Morphological Characteristics Of Human Femoropopliteal Arteries, Sayed Ahmadreza Razian, Majid Jadidi, Alexey Kamenskiy

UNO Student Research and Creative Activity Fair

Background: Disease of the lower extremity arteries (Peripheral Arterial Disease, PAD) is associated with high morbidity and mortality. During disease development, the arteries adapt by changing their diameter, wall thickness, and residual deformations, but the effects of demographics and risk factors on this process are not clear.

Methods: Superficial femoral arteries from 736 subjects (505 male, 231 female, 12 to 99 years old, average age 51±17.8 years) and the associated demographic and risk factor variables were used to construct machine learning (ML) regression models that predicted morphological characteristics (diameter, wall thickness, and longitudinal opening angle resulting from the …

Development Of A Crosslinked Osteochondral Xenograft And A Collagen Stabilizing Intra-Articular Injection To Remediate Cartilage Focal Lesions To Prevent Osteoarthritis, Mark Lewis Mosher

Theses and Dissertations

Osteoarthritis is one of the most common causes of disability in adults in America. It is a progressive and degenerative disease where the articular cartilage is broken down and lost from the surfaces of bones causing chronic pain and swelling in the joints, and currently has no cure. The most commonly osteoarthritis starts from a focal lesion on the cartilage surface, which will expand on the surface and downwards through the thickness of the tissue. The current gold standard for correcting cartilage focal lesions is the osteochondral autograft/allograft transplantation (OAT), which replaces the defect with a fresh osteochondral graft. The …

In Vitro Bioreactor For Mechanical Control And Characterization Of Tissue Constructs, Samuel Coeyman

All Dissertations

Heart failure (HF) currently affects over 6 million Americans, 50% of whom die within 5 years of their initial diagnosis. A major contributor to the onset of HF is cardiac fibrosis in the myocardium, which arises when fibroblasts (FBs) are activated in response to heightened mechanical stress from overload conditions like hypertension. Activated FBs remodel the extracellular matrix (ECM) and secrete ECM proteins including collagen. FB remodeling has been studied in the past by applying forces and/or deformations to three-dimensional, cell-seeded gels and tissue constructs in vitro. Unfortunately, previous stretching platforms have traditionally not enabled mechanical property assessment to be …

The Interaction Of Angiotensin I And Ii On Calcified Aortic Valve Cells, Fah Sysavanh

Biomedical Engineering Undergraduate Honors Theses

Cardiovascular diseases affect the older population with limited treatments available. Aortic valve stenosis is a cardiovascular disease in which the aortic valve narrows, causing blood flow constriction and calcification.¹ The only treatment is to replace the valve, which can be costly and lead to other health complications.

The renin-angiotensin system (RAS) is a pathway that helps with maintaining cardiovascular homeostasis. Angiotensin I (ANGI) and II (ANGII) are hormones in the RAS that cause an increase in inflammation, stress, and blood pressure by binding to the Angiotensin Type 1 Receptor (AT1R).¹ Gelatin-based valve thin film (vTF) platforms were fabricated to investigate …

Design Of A Four Channel Pulsatile Perfusion Bioreactor For Ex-Vivo Study Of Vascular Grafts, Thomas M. Fair

All Theses

Cardiovascular diseases are the leading cause of death in the United States. Atherosclerosis in peripheral arteries is a major contributing factor. Autologous saphenous vein grafts are the most common bypass grafts for treating peripheral artery diseases. A quarter of these grafts fail within a year, and around half have failed within 10 years of the initial surgery. Graft failure is attributed to the development of intimal hyperplasia indicated by the migration and proliferation of vascular smooth muscle cells, fibroblasts, and the deposition of extracellular proteins.

Increases in flow, pressure, the pulse frequency, and the differential of pressure that model an …

Bone And Cartilage Compression Simulator, Karoline M. Wucherer, Benjamin A. Parmentier, Thomasina E. Hinkle

Biomedical Engineering

A device was developed that delivers mechanical loads to bone and soft tissue samples under physiological conditions to aid in the research of tissue engineering bone and cartilage. To begin the design process, a Network Diagram and Gantt Chart were produced to create a general timeline for the project to follow. This allowed us to measure our progress and determine what effects (if any) delays could have on our project.

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 …

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, …

A Single Cell Pair Mechanical Interrogation Platform To Study Cell–Cell Adhesion Mechanics, Amir Monemianesfahani

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

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

Developing Aligned Nerve Scaffolds In A 3d Type-I Collagen Gel, Gabriel David

Biomedical Engineering Undergraduate Honors Theses

Despite significant progress in the field of peripheral nerve repair, clinical success is still limited, leaving millions to suffer from peripheral neuropathy with billions spent every year for treatment. Nerve repair methods that are capable of maximizing the regenerative properties of peripheral nerves are greatly desired in the field of medical science. This research aims to fill the gap between modern methods and the future of nerve repair by creating type-I collagen scaffolds with aligned degradation pores that will assist and nurture nerves growing through them. This is achieved by incorporating adipose stem cells into type-I collagen hydrogels and aligning …

Quantifying The Effect Of Intrinsic Aging On Skin Microstructure And Mechanical Function Using Multiphoton Microscopy, Alan Edward Woessner

Graduate Theses and Dissertations

Over the next couple of decades, the number of elderly individuals is expected to double, bringing increased healthcare spending due to seemingly minor injuries to skin. In skin, the 3D dermal collagen fiber network, which is the primary load-bearing structure, undergoes changes in organization and composition due to intrinsic aging. However, the relationships between altered microstructure and mechanical function is not well understood. Quantitative imaging techniques have been used in the past to link skin structure to mechanical function, but previous analysis has been limited to 2D assessments. Multiphoton microscopy (MPM) is a non-destructive imaging technique with intrinsic depth-sectioning capabilities, …

3d Printable And Computational Models Of The Bone Marrow Mechanical Environment, Alexander Regner

Boise State University Theses and Dissertations

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in part regulated by mesenchymal stem cells (MSCs). We reported that daily low intensity vibration (LIV) restores MSC proliferation in senescence and simulated microgravity models, suggesting reduced mechanical signal delivery to MSCs likely contributes to declining bone mechanoresponse. To this end, we have developed a 3D bone marrow analog which controls trabecular geometry, marrow mechanics and external stimuli.

Finite element (FE) models of hydrogels, representing bone marrow, were generated using instantaneous compression (1000% strain/s, 20% strain) and relaxation experiments (100s) of both gelatin and hyaluronin-based hydrogels. …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Injectable Gelatin-Silk Fibroin Composite Hydrogels For In Situ Cell Encapsulation, Ryann D. Boudreau

Honors Theses and Capstones

Hydrogels are widely used tools for tissue engineering and regenerative medicine. Characterized as biofunctional, water-based polymer matrices with tunable mechanical properties, hydrogels have promising but limited applications in biomedical engineering, due to poor and static matrix strength. Here we plan to rectify this issue by introducing a new hydrogel made from a composite of gelatin and silk fibroin crosslinked by microbial transglutaminase (mTG) instantly and beta sheet formation gradually, respectively. This interpenetrating network (IPN) shows enhanced mechanical stiffness and strength compared to gelatin hydrogels, and is capable of encapsulating human cells with high viability demonstrated by the encapsulation of human …