Molecular, Cellular, and Tissue Engineering Commons^™

Mitral Annular Calcification In Diabetes: Valvular Interstitial Cells, Antioxidant Therapy, And Tissue Engineering Approaches, Raleigh J. Keenan

All Theses

Mitral annular calcification (MAC) is a chronic, progressive, and degenerative condition that impairs mitral valve function and increases the risk of cardiovascular disease. The mitral annulus is a saddle-shaped, fibrous structure that is primarily composed of collagen and elastin. The annulus also contains interspersed lipids that are involved in cellular metabolism, as well as inflammatory and osteogenic signaling. These lipids increase the annulus’ susceptibility to calcification, under conditions that increase mechanical stress (hypertension) and promote atherosclerosis (diabetes mellitus). These conditions intensify calcification by promoting the activation of valvular interstitial cells (VICs), increasing fibrosis, and inducing osteogenic differentiation. Although it is …

Novel Electrospinning Techniques For Fabricating Scaffolds To Model Intracranial Atherosclerotic Disease In Tissue Engineered Blood Vessel Mimics, Isaac "Squeaky" Buentipo

Master's Theses

Novel Electrospinning Techniques for Fabricating Scaffolds to Model Intracranial

Atherosclerotic Disease in Tissue Engineered Blood Vessel Mimics

Isaac “Squeaky” Buentipo

Dr. Kristen Cardinal’s Tissue Engineering Lab at California Polytechnic State University specializes in fabricating customized vascular models, known as Blood Vessel Mimics (BVMs), for medical device testing. BVMs are simplified in vitro vascular models designed to bridge the gap between bench testing and in vivo evaluation of intravascular medical devices. BVMs are produced by combining a polymer scaffold with human vascular cells. Through novel scaffold fabrication techniques, such as silicone injection molding, silicone dip casting and electrospinning, the capabilities of …

Fabricating Silver-Ceria Polymer Nanocomposite Scaffolds For Biomedical Therapeutic Applications, Shreya S. Pawar

Honors Undergraduate Theses

Improper healing of bone fractures and limited regeneration of bone following bone tumor resection remain a prevalent complication worldwide. Long-term effects of this include joint instability, limited movement, and arthritis. Bone infections (osteomyelitis), reactive oxygen species (ROS) generation via excessive inflammation, and underlying conditions such as osteoporosis can contribute to suboptimal bone tissue regeneration. ROS accumulation stimulates osteoblast apoptosis, while promoting osteoclast differentiation. These processes inhibit mineralization and osteogenesis. Conventional therapeutics involve the utilization of drugs and bone grafts. However, these approaches pose limitations and can result in subsequent complications. Microbial infections, ROS accumulation, and excessive inflammations are factors that …

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 …

Tissue-Engineered Models For Investigating Nerve Infiltration In Fibrotic Microenvironments, Nikolas Ala-Kokko

Graduate Theses and Dissertations

Neuron infiltration is involved in a multitude of diseased states and is critical in the regeneration of physiologic conditions. Modeling of innervation in three-dimensional, heterogenous, environments would allow early investigation in the crosstalk of neurons and native cells in normal and pathophysiologic microenvironments to gain an understanding of mechanistic functions. This would allow for greater insight into the role of metabolism, cell adhesion, microenvironmental alternations, cellular crosstalk, and signaling pathways that play a role in the promotion and prevention of neurite growth. In this thesis, with the construction of collagen-based hydrogels as the foundation for cell culture, we investigate cell …

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 …

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 …

Preparing Homogenous Composites Of Collagen And Cellulose Nanocrystals For Tissue Engineering Research, Zachary Stanley

Biological and Agricultural Engineering Undergraduate Honors Theses

Advancements in medicine and our understanding of stem cells have led to a greater emphasis on further developing research focused on tissue engineering. This research has led to the rise of both two-dimensional and three-dimensional scaffolds that can be utilized to repair bone, skin, vascular, and potentially even nervous tissue. One of the prominent compounds used in modern scaffolds is collagen-based hydrogels due to their low antigenicity and ability to provide structure to cells. There is potential to further improve upon this three-dimensional scaffold by incorporating cellulose nanocrystals (CNCs) into a composite hydrogel with collagen. The addition would increase 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 …

Development Of A Tissue Engineered Cardiac Patch, Howard Herbert

All Dissertations

Cardiovascular Disease(CVD) is the leading cause of mortality in the developed world. CVD is most commonly manifested as atherosclerosis of the coronary arteries leading to Myocardial Infarction(MI). After MI, fibrosis of the ventricular wall leads to heart failure(HF), a pandemic affecting 26 million people globally. While therapies are continuously developed to combat HF, the treatment of choice, whole heart transplant, is limited by the availability of donor hearts. It is clear that there is a need to develop a long-term solution to combat HF and its enormous economic burden. Tissue Engineering and Regenerative Medicine holds promise as a possible solution …

Fumarate-Based Polymers: Oligo(Poly(Ethylene Glycol) Fumarate) And Poly(Butylene Fumarate) For Tissue Engineering Heart Valve And Bone Tissue, Christian T. Denny

Biomedical Engineering ETDs

Tissue engineering is an emerging field that came from the fields of medicine, materials science, and engineering. The foundation of tissue engineering uses a paradigm that incorporates cells, biomaterials, and exogenous factors to create living tissues for medical, pharmaceutical, and research purposes. Within the last 100 years, biomaterials have been developed to solve many medical and research problems. As biomaterials have developed throughout the years new materials have been developed to have specific properties appropriate for medical applications. Fumarate is a naturally derived molecule in the body and has been found useful for developing polyesters that can be crosslinked into …

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.

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 …

Tissue Engineering And The Effect Of Volumetric Muscle Loss On Muscle Performance, Alex Pemberton

Biomedical Engineering Undergraduate Honors Theses

Trauma, for so many people, creates life altering injuries. One of the major injuries that results from trauma is volumetric muscle loss (VML), which is the loss of muscle tissue that cannot be naturally regenerated and results in chronic loss of function. When a small amount of damage is done to a muscle, but the underlying extracellular matrix of the cell is still intact, the muscle can regenerate much of its volume and function. If the injury damages the extracellular matrix, the injury site is instead filled with scar tissue, which cannot regenerate muscle mass or function. Seen widely in …

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 …

Peptoid-Based Microsphere Coatings For Biomaterial Applications, Jesse Leland Roberts

Graduate Theses and Dissertations

Peptoids are peptidomimetic oligomers that predominantly harness similarities to peptides for biomimetic functionality. The incorporation of chiral, aromatic side chains in the peptoid sequence allows for the formation of distinct secondary structures and self-assembly into supramolecular assemblies, including microspheres. Peptoid microspheres can be coated onto substrates for potential use in biosensor technologies, tissue engineering platforms, and drug-delivery systems. They have the potential for use in biomedical applications due to their resistance to proteolytic degradation and low immunogenicity. This dissertation focuses on the physical characteristics and robustness of the peptoid microsphere coatings in various physiological conditions, along with their ability to …

Using A Lubricin Reporter Cell To Test Current Vs. Optimized Media Compositions, Sean M. Kennedy

Honors Undergraduate Theses

Osteoarthritis is a joint disease characterized by the breakdown of articular cartilage. The field of tissue engineering is interested in developing methods to produce biological alternatives to current orthopedic procedures. Lubricin is a molecule which is important in the proper lubrication of articular cartilage. It is a challenge in the field of tissue engineering to produce cartilage with sufficient lubricin expression. Developing a reporter cell for lubricin allowed for a more efficient investigation of the conditions wh­­­ich may influence its expression. By comparing "optimized" and traditional media solutions, it was determined that the use of a previously reported type II …

Development Of An Injectable Methylcellulose Hydrogel System For Nucleus Pulposus Repair And Regeneration, Nada A. Haq-Siddiqi

Dissertations and Theses

Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic …

Design Of An Affordable Rotating Drum Electrospinner For Classroom Education, Peder Solberg

The Journal of Undergraduate Research

Electrospinning is a technology used to generate small fibers down to nano-scale size. This method of fiber creation has been around for many years. However, in recent years electrospinning has found increased applications, especially in the area of tissue engineering due to its ability to create fibers with properties similar to the extracellular matrix in tissue. An electrospinning platform can illustrate concepts of engineering, electro-mechanical system design, manufacturing, and biomedical applications in one single package. Hence, it provides an excellent opportunity to integrate into secondary (middle and high school) and post-secondary (undergraduate) technology education.

Furthermore, just as integration of 3D …

Artificial Synthetic Scaffolds For Tissue Engineering Application Emphasizing The Role Of Biophysical Cues, Samerender Nagam Hanumantharao

Dissertations, Master's Theses and Master's Reports

The mechanotransduction of cells is the intrinsic ability of cells to convert the mechanical signals provided by the surrounding matrix and other cells into biochemical signals that affect several distinct processes such as tumorigenesis, wound healing, and organ formation. The use of biomaterials as an artificial scaffold for cell attachment, differentiation and proliferation provides a tool to modulate and understand the mechanotransduction pathways, develop better in vitro models and clinical remedies. The effect of topographical cues and stiffness was investigated in fibroblasts using polycaprolactone (PCL)- Polyaniline (PANI) based scaffolds that were fabricated using a self-assembly method and electrospinning. Through this …

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 …

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease or …

Using Crosslinked Hyaluronic Acid (Ha) And Collagen Scaffolds With Sustained Brain-Derived Neurotrophic Factor (Bdnf) Release For Post-Sci Nerve Regeneration, Panth Doshi

Undergraduate Research Posters

Traumatic events resulting in spinal cord injuries (SCIs) often leave people paralyzed or with partial loss of motor function. The physical disabilities arising from traumatic events prevent people from functioning at the same level as pre-injury. My work aims to identify a plausible method to overcome the inhibitory post-SCI environment and to regenerate nervous tissue in order to restore neural function and, subsequently, motor function. I identified components of a new, hypothetical nerve scaffold based on the immune response after SCIs and the efficacy of currently used scaffolds for nerve regeneration. Hyaluronic acid (HA) polymer scaffolds and collagen-based scaffolds are …

Ultrasonically Responsive Tissue Engineering Scaffolds For The Temporal Control Over Osteo-Inductive Growth Factor Delivery, Catherine Linh

Senior Honors Projects

In 2012, approximately 6.8 million people in the United States were diagnosed with orthopedic injuries or diseases. Over 500,000 people in the United States underwent bone grafting procedures, which cost 2.5 billion dollars per year and can result in complications. Polymer-based grafting scaffolds can facilitate 3D bone tissue growth in a localized, sustained manner. However, bone regeneration requires the orchestration of a sequence of events. Current scaffolds based on degradation and diffusion cannot provide sequential deliveries. We aimed to design a polymer scaffold that can release one payload diffusively at early time points, followed by ultrasonically triggered release of a …

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 …

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 …

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 …

Development And Characterization Of An In-House Custom Bioreactor For The Cultivation Of A Tissue Engineered Blood-Brain Barrier, Amin Hadi Mirzaaghaeian

Master's Theses

The development of treatments for neurological disorders such as Alzheimer’s and Parkinson’s disease begins by understanding what these diseases affect and the consequences of further manifestation. One particular region where these diseases can produce substantial problems is the blood-brain barrier (BBB). The BBB is the selective diffusion barrier between the circulating blood and the brain. The barrier’s main function is to maintain CNS homeostasis and protect the brain from the extracellular environment. The progression of BBB research has advanced to the point where many have modeled the BBB in vitro with aims of further characterizing and testing the barrier. Particularly, …

Development And Characterization Of Plga And Eptfe Blood Vessel Mimics Using Gene Expression Analysis, Michael Gibbons, Sarah Ur

Biomedical Engineering

Tissue engineered blood vessels (TEBV’s) have the potential to act not only as a replacement for diseased vessels, but also as a testing platform for intravascular devices such as stents. To this end, the goal of this study was to develop protocols for the construction of TEBV’s composed of human vascular cells and either expanded polytetrafluoroethylene (ePTFE) or poly-lactic-co-glycolic acid (PLGA), as well as a protocol for gene expression in those TEBV’s. Initial experiments involved only human umbilical vein endothelial cells (HUVEC’s), but after low cell confluency and spreading in single-sodded vessels a second cell type, human umbilical vein smooth …