Biomedical Engineering and Bioengineering Commons^™

Development Of An In Vitro 3-Dimensional Co-Culture Human Colorectal Cancer Model In Microfluidic Devices, Abby Jens

Master's Theses

Colorectal cancer is the second most common cause of cancer-related deaths in the United States, with the relative 5-year survival rate for distant stage cancer being only 14%. The most common treatment for colorectal cancer is with chemotherapeutic drugs; however, the discovery of these drugs is costly, time-consuming, and often requires the use of animal models that do not yield results that translate to clinical trials. Due to these shortcomings, researchers seek to develop physiologically relevant in vitro tumor models that more accurately mimic the tumor microenvironment for cheaper and faster high-throughput drug screening. The aim of this research was …

Development Of An Angiogenic Tissue-On-A-Chip Microenvironment, Eric Stuehr

Master's Theses

Preclinical testing is necessary to investigate the safety and efficacy of novel therapeutics before moving to clinical trials, yet approximately 90% of these therapies fail once tested in humans. This has led to increased interest in developing robust preclinical models that accurately mimic the complex human in vivo physiology. Microfluidic devices that can introduce dynamic conditions to 3D cell/organoid cultures, also known as tissue-on-a-chip, have emerged as physiologically relevant in vitro preclinical models that can achieve high throughput screening of therapeutics. The research presented here aimed to develop an angiogenic environment within a novel microfluidic device to stimulate formation of …

Implementation Of Methods For Cell Therapy Research And Assessment Of The Impact Of Cryopreservation, Samantha Lynes

Master's Theses

Cell therapy is the administration of living cells into a patient to prevent or treat a variety of diseases and illnesses. The cell therapy industry is rapidly expanding, and continued research is necessary for manufacturing safe and effective therapies. Although cell therapy manufacturing generally involves cryopreservation processes for storage, there are limited standards for cryopreservation processes and assays required to evaluate cell therapies post-thaw, and limited understanding exists about how a recovery period post-thaw could impact cell health. The overall goal of this thesis was to evaluate the effect of cryopreservation and potential subsequent recovery time on cell viability.

Because …

Hypoxic Incubation Chamber, Simone Lisette Helfrich, Makenzie Nicole Jones

Biomedical Engineering: Graduate Reports and Projects

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the …

Hypoxic Incubation Chamber, Simone Lisette Helfrich, Makenzie Nicole Jones

Master's Theses

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the …

Optimization Of A Novel Nipam-Based Thermoresponsive Copolymer For Intramuscular Injection As A Myoblast Delivery Vehicle To Combat Peripheral Artery Occlusive Disease, Quentin R. Klueter

Master's Theses

There is a need for a minimally invasive delivery method to enable cell therapies to combat peripheral artery occlusive disease (PAOD) in end stage patients. Myoblasts show promise as a cell mediated therapy but warrant an improved delivery method to increase cell retention in the region of interest because of their adherent nature, relative to previously used BM-MNC’s that are non-adherent. Contemporary issues with achieving successful cell therapies of vasculature can be mainly characterized by the lack of clinical translation from promising animal studies and absence of cell delivery scaffolding. Naturally, polymers have been widely experimented with as grafts to …

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.

Assessing The Effects Of Oxaliplatin On An In Vitro Three-Dimensional Human Colorectal Cancer Model, Sabrina Nelson

Master's Theses

Colorectal cancer is the third most common cancer in the United States with a 5-year late-stage survival rate of only 14%. Due to the lack of translation between animal models and clinical trials as well as the inefficacy of many chemotherapeutics in initial clinical trials, researchers are turning to in vitro drug screening models in an effort to mimic the conditions in vivo. This research project aimed to validate an in vitro tumor culture model within a microfluidic device using a clinically relevant chemotherapy drug. The first experiment consisted of a cell density and drug concentration study to determine …

The Impact Of Myoblast Transplantation On Collateral Capillary Arteriogenesis And Macrophage Phenotype, Christine Hue Do

Biomedical Engineering

Gangrene, pain, loss of limb function, amputation, and death are only few of the grievous consequences associated with peripheral arterial disease (PAD), a vascular disease caused by an obstruction that narrows the blood vessels. Since some patients have collateral vessels that can re-route blood to its downstream destination, much focus has been spotlighted upon discovering the mechanism of this process, termed arteriogenesis, as well as cell therapies to increase arterial diameter of collateral vessels. Since some patients do not have native pre-existing collateral vessels, another method to re-route blood is through arterialized collateral capillaries (ACC), which is the conversion of …

Studying The Efficacy Of An Injectable 3-Dimensional Fibrin Extracellular Matrix To Characterize The Effects Of Antitumor Agents On Sw620 Cells In A Microfluidic Device, Thèo Anastos

Master's Theses

Colorectal cancer is the third most common cancer in the United States and there is currently a lot of research going into new antitumor agents to kill the cancer. One method for replicating the tumor response to a drug in vivo is by creating an in vitro drug testing model to replicate the in vivo condition. This research project was conducted to determine the efficacy of testing tumor cultures in a microfluidic device as a way to provide accurate drug responses in vitro instead of using in vivo subjects in clinical trials. A total of four experiments were conducted with …

Development Of A Robust Methodology To Obtain And Assess Myogenic Precursor Cells For Their Use In Regenerative Therapies, Ricardo Lasa

Master's Theses

Peripheral arterial occlusive disease (PAOD) is characterized by buildup of atherosclerotic plaque in peripheral arteries that leads to an occlusion that can interrupt the supply of blood to the peripheral tissue, causing downstream tissue ischemia/hypoxia. PAOD is estimated to affect over 200 million patients worldwide. Current surgical revascularization treatments can be effective in about half of the patient population, leading to a significant number of patients with no treatment options beyond pharmacological intervention and lifestyle modification. The decrease in blood flow downstream of the occlusion leads to increased blood pressure gradient in the microvasculature, specifically in vessels that connect arterial …

Development And Optimization Of Imaging And Image Quantification Techniques For Tissue-Engineered Blood Vessel Mimics, Ashley Turcott

Master's Theses

Blood vessels mimics (BVMs) are tissue-engineered blood vessels used to test vascular devices in an environment that mimics some simple anatomical factors of native blood vessels. It is important to accurately and consistently assess tissue-engineered blood vessels, although there is currently a lack of standardization in Cal Poly’s Tissue Engineering Lab and in the entirety of the field. The goal of this thesis was to develop and optimize imaging and image quantification techniques for tissue-engineered blood vessels.

The first aim of this thesis optimized and compared imaging and assessment techniques for electrospun scaffolds. Images from different SEMs were compared to …

Investigation Of Experimental Variation Of Bovine Sphingomyelin As A Novel Ingredient For Ultraviolet Protection, Esther Chen

Master's Theses

Skin cancer is a prevalent disease that globally affects 2-3 million people per year [1]. This number is expected to grow tenfold as depletion of the ozone layer contributes to harsher rays reaching Earth’s surface [2]. A common way to protect against those ultraviolet waves is to apply sunscreen, however, recent reports call into question the safety of some active ingredients as they can enter through the skin into the bloodstream [3]. This thesis aims to investigate an alternative solution that uses bovine sphingomyelin (BSM) as photoprotective solution against UV irradiation.

In order to evaluate the effectiveness of BSM against …

Mechanisms Of Reduced Vascular Tone Following Arteriogenesis Induced By Femoral Artery Ligation, Christopher Hatch

Biomedical Engineering

The presence of a developed, native collateral network can decrease the severity of ischemic injury proceeding arterial occlusion. The collateral network must under arteriogenesis to enlarge and increase blood flow to the ischemic region. Although there has been tremendous effort attempting to understand the mechanisms of arteriogenesis, no therapies have been successful in improving patient outcome. To better understand the mechanisms involved in arteriogenesis, the effect of nitric oxide production, myogenic tone, and a-adrenergic receptors were evaluated as these have been identified as playing an important role in vascular injury. Arteriogenesis was induced by ligating the femoral artery between the …

Evaluation Of Human Umbilical Vein Endothelial Cells In Blood Vessel Mimics Through Changes In Gene Expression And Caspase Activity, Conor Charles Hedigan

Master's Theses

Blood vessel mimics (BVMs) are simple tissue engineered blood vessel constructs intended for preclinical testing of vascular devices. This thesis developed and implemented methods to characterize two of these components. The first aim of this thesis investigated the effect of cell culture duration and flow conditions on endothelial cell gene expression, especially regarding endothelial-to-mesenchymal transition (EndMT). A trend of decreased endothelial marker gene expression and increased mesenchymal marker gene expression would indicate EndMT. qPCR analysis revealed that increased cell culture duration did not result in EndMT, and in fact increased endothelial marker expression as cell culture duration increased. Disturbed flow …

Plga Scaffold Device, Tyler D. Tackabery, Bryce Powada, Tate Morell

Biomedical Engineering

No abstract provided.

Fluid Delivery System For A Cell Culture On A Microfluidic Chip, Austin J. Roeder, Colleen A. Richards, Emily A. Matteson

Biomedical Engineering

This project report provides a description of the progress made in the development of a fluid delivery system for a microfluidic cell culture on a chip. The system is intended to be used in a humidified incubator in a university laboratory and the fluid delivery system is required to exist and operate within that incubator for extended periods of time. Therefore, the system will be gravity-driven and contain no electronic components. The key specification of the system is to provide fluid flow at a constant velocity.

After manufacturing and testing the device, all specifications were met except for the fluid …

Pressure Cylinder Controlled Release Valve, Alexa Dominique Balbuena

Biomedical Engineering

This project aims to integrate an automatic gas release system in a pre-existing scaffold fabrication process for tissue engineering applications.

To form the proper scaffold structure, the fabrication process is heavily influenced by the change in its surrounding pressure. The current production involves a pressure transducer and electric valve that is managed manually to create a suitable pressure environment for the scaffold. This method, although functional, proves to be ineffective when creating several batches; the user needs to constantly monitor the developing pressure profile and alter voltage parameters accordingly to create a linear gas release under a predetermined slope.

To …

In Vitro Growth Of Osteoblasts On Poly Lactic-Co-Glycolic Acid Scaffolds Created Via Gas Foaming, Matthew James Thomas

Master's Theses

This study analyzed the feasibility of using gas foaming to create Poly Lactic-co-Glycolic Acid (PLGA) scaffolds for use as a substrate in bone tissue engineering and set out to determine whether the presence of osteoblasts on these scaffolds enhanced their material stiffness. The process of bone formation involves osteoblasts depositing extracellular matrix and calcifying this matrix with calcium phosphate crystals (Hasegawa et al., 2017) and pits between 30-40μm in diameter on tissue engineering scaffold surfaces have been shown to best promote osteogenic activity in the presence of bone-forming cells (Halai et al., 2014).The scaffolds were determined to contain pits within …

Influence Of Fibroblasts On Functional Arteriogenesis In A Murine Chronic Hindlimb Ischemia Model, Ashli A. Santos

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs when there is a narrowing or blockage – usually a buildup of plaque - within the arteries that reduces blood flow to tissues which can chronic ischemia. As with most diseases, early detection and proactive treatment are important to maximize prognosis. Exercise effectively treats PAOD, but due to ischemic pain in the limbs, or intermittent claudication (IC), exercise can become painful and difficult. Due to the buildup of plaque, occlusions create an ischemic environment that changes the pressure distribution in collateral networks and increases the shear stress in transverse collaterals. Those two responses signal …

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 …

Development And Characterization Of Tissue Engineered Blood Vessel Mimics Under "Diabetic" Conditions, Shelby Gabrielle Kunz

Master's Theses

The development of tissue engineered blood vessel mimics for the testing of intravascular devices in vitro has been established in the Cal Poly tissue engineering lab. Due to the prevalence of cardiovascular disease in diabetic patients and minimal accessible studies regarding the interactions between diabetes and intravascular devices used to treat vascular disease, there is a need for the development of diabetic models that more accurately represents diabetic processes occurring in the blood vessels, primarily endothelial dysfunction. This thesis aimed to create a diabetic blood vessel mimic by implementing a high glucose environment for culturing human endothelial cells from healthy …

Microvascular Topology And Intravascular Endothelial Cell Labeling In The Gracilis Anterior Muscle Of Balb/C Mice, Paul Heckler Ii

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) affects approximately 200 million individuals globally. The major underlying cause of PAOD is an inflammatory disease known as atherosclerosis, which results from the build-up of low-density lipoproteins (LDL) in the sub-intimal space. This initiates a complex cascade of events that lead to plaque growth. Plaque growth can then expand into the lumen of the vessel and result in occlusion and/or thrombosis. Symptoms of the disease can include claudication, ulcers, and/or gangrene, although many patients are asymptomatic. Similar to other forms of ischemic disease, risk factors for PAOD include hypertension, diabetes, and smoking. Common treatments include …

Functional Vasodilation Is Impaired In Arterialized Capillaries In The Spinotrapezius, Joshua P. Cutts

Biomedical Engineering

Ischemic diseases are the result of atherosclerotic plaques, which occlude conduit arteries. Ischemic disease in different tissues leads to different conditions, such as coronary artery disease (CHD), cerebrovascular disease (CVD), and peripheral arterial occlusive disease (PAOD). Patient vasculature architecture is variable; some patients having many collateral vessels, which are connect one arterial branch to another, and readily serve as natural bypass routes to atherosclerotic occlusions, to enlarge and provide blood flow to tissue distal to the occlusion. Patients with many natural collateral vessels are ischemia protected. Unfortunately, not all patients have collateral arterioles to remodel into conduit vessels and provide …

Development And Implementation Of Assessment Methods For Tissue-Engineered Blood Vessel Mimics, Tanner Stevenson

Biomedical Engineering

Coronary Artery Disease (CAD), the most prevalent form of heart disease, is the result of clogged or damaged coronary arteries and claims around 380,000 Americans annually. A common treatment for CAD involves placing a stent into the artery in order to open the lumen and support the native tissue—a procedure that drastically reduces patient recovery times in comparison to heart bypass surgery. However, stents do not always interact well with the body and require additions such as surface coatings or drug elution in order for additional biocompatibility. These additions necessitate extensive in vitro and in vivo testing which are expensive …

Matrix Remodeling Accompanies In Vitro Articular Cartilage Spherical Shaping, Nathan Thomas Balcom

Master's Theses

Introduction: Articular cartilage (AC) is a low friction load bearing material found in synovial joints. The natural repair of damaged tissue is difficult and often requires surgical intervention. With large defects it becomes necessary to match the original tissue geometry. We hypothesized that localized collagen (COL) and/or proteoglycan (PG) remodeling occurs during AC spherical reshaping. The objective of this study was to determine the presence, magnitude and depth dependence of COL and PG remodeling that accompanies AC reshaping. Methods: Full thickness AC blocks (7x7 mm² surface area) were harvested from the ridges of the patellofemoral groove of immature (1-3 …

Shelf Life Study Of Electrospun Plga Copolymers, Sean Youra, Nick Hudson

Biomedical Engineering

Poly(lactic-co-glycolic acid) (PLGA) is one of the most commonly used copolymers for electrospinning in tissue engineering applications. However, most research has not focused on the copolymer itself in regards to how long it can be used effectively and if varying the concentrations of polylactic acid (PLA) and polyglycolic acid (PGA) affect the resulting properties. Electrospinning is the method we use to create the three-dimensional constructs, or “scaffolds”, for the blood vessel mimic (BVM) in the tissue engineering lab. The aim of our project was to investigate if the morphology and mechanical properties of the scaffolds changed over time when they …

Investigating The Reproducibility Of The Current Bvm Protocol, Corey Gross

Biomedical Engineering

Coronary Artery Disease (CAD) is responsible for 1 death every minute in the US. Angioplasty with the implantation of stents is a common treatment method for CAD. Although there is a variety of stents currently on the market, there is still a need to develop new types for different pathologic conditions. Preliminary assessment of the physiological response to new stents is needed as they are being developed. The FDA approval process implemented today is a long, tedious path with a range of testing methods that include static in vitro testing and high-cost animal testing. Tissue engineered blood vessels have been …

Characterization Of Tight Junction Formation In An In-Vitro Model Of The Blood-Brain Barrier, Michael Robert Machado

Master's Theses

Active and passive transport of substances between the microcirculation in the brain and the central nervous system is regulated by the Blood-Brain Barrier (BBB). This barrier allows for chronic and acute modulation of the CNS microenvironment, and protects the brain from potentially noxious compounds carried in the circulatory system. In-vitro modeling of the BBB has become the target of much research over the past decade, as there are many unanswered questions regarding modulations in the permeability of this barrier. Additionally, the development of a practical and inexpensive model of the BBB would facilitate a much more efficient drug development process. …

Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing, Navid Djassemi

Master's Theses

Tissue Engineering A Blood Vessel Mimic While Monitoring Contamination Through Sterility Assurance Testing

Navid Djassemi

Tissue engineering blood vessel mimics has been proposed as a method to analyze the endothelial cell response to intravascular devices that are used in today’s clinical settings for the treatment of cardiovascular disease. Thus, the development of in vitro blood vessel mimics (BVMs) in Cal Poly’s Tissue Engineering Lab has introduced the possibility of assessing the characteristics of cellular response to past, present, and future intravascular devices that aim at treating coronary artery disease.

This thesis aimed at improving the methods and procedures utilized in …