Biomedical Engineering and Bioengineering 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 …

3d Bioprinting Of Hydrogel Scaffold Skin Equivalents For Cosmetic And Drug Testing, Allison Reno

All Dissertations

Tissue engineering scaffolds are a crucial element of generating larger 3D tissue equivalents for modeling and clinical grafting. Currently, much of scaffold technology has not been significantly updated since the introduction of manually pipetted hydrogels and electrospun fiber scaffolds. Both of these approaches have their advantages and disadvantages, but neither utilize emerging biofabrication techniques such as advanced 3D bioprinting and plotting. In addition to more precision in the outer geometries of the scaffold, the use of bioprinting also introduces the ability to shape hydrogels into very intricate porous inner patterns within the outer geometries. This allows for the design of …

Optimizing A Perfusion-Compression Bioreactor Via Python Integration, Umamah Amer

Honors Theses

Bioreactors are widely used in tissue engineering to support cell and tissue growth under controlled conditions. Perfusion-compression bioreactors, like the one developed in our lab, can be used to replicate the physiological loading of bone on 3D-printed scaffolds. When seeded with osteogenic cells and subjected to mechanical loading, these scaffolds serve as a model to study osteogenesis. To simulate physiological conditions, the bioreactor must apply 1000 compression cycles at forces up to 200 N, three times daily over 14 days. Upon implementation, validation testing and experimental studies exposed several limitations in the bioreactor’s control code. The system was initially programmed …

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 …

Insights Into The Characterization And Degradation Of Electrospun Polycaprolactone Scaffolds For Tissue Engineering Applications, Caleb B. Wells

Theses and Dissertations

Electrospun polymeric biodegradable scaffolds are essential in tissue engineering, particularly for Engineered Tissue Vascular Grafts (ETVGs), which promise advancements in treating coronary artery disease, peripheral arterial disease, congenital cardiovascular defects, and renal disease. These scaffolds present a solution to issues with autologous graft availability and durability. While large-diameter grafts in low-pressure environments have seen success, small-diameter grafts in high-flow scenarios remain challenging. Understanding polymeric scaffold degradation and behavior during incubation, especially under dynamic mechanical loading, is vital for clinical translation of small-caliber ETVGs.

This research focuses on characterizing the mechanical and microstructural properties of electrospun polycaprolactone (PCL) scaffolds and their …

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 …

Evaluation Of Polyvinyl Alcohol (Pva) For Electrospinning Utility In The Blood Vessel Mimic (Bvm) Lab, Logan Vandenbroucke

Master's Theses

Electrospinning has provided the opportunity to create extracellular matrix (ECM) mimicking scaffolds for the development of tissue-engineered constructs. Within Professor Kristen Cardinal’s Blood Vessel Mimic (BVM) Lab, at Cal Poly, there exists a constant demand for innovation and the expansion of polymer types and electrospinning capabilities for its BVM model. Along these lines, the BVM Lab has recently acquired two new electrospinning systems: the Spinbox, a commercially graded electrospinning system, and the Learn-By-Doing system, which was part of a recently completed thesis conducted by Jason Provol. Additionally, recently published literature has demonstrated polyvinyl alcohol (PVA) as a viable option for …

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 …

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 …

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 …

Development Of A Vascularized Osteogenic Implant Using Fused Glycosaminoglycan-Chitosan Microcapsules, Charles Michael Gabrion

Wayne State University Theses

Osteoarthritis remains a poorly treatable outcome of traumatic cartilage injury as cartilage is unable to self-repair. Unfortunately, roughly 10% of all adults in the United States have been diagnosed with osteoarthritis although the true fraction is likely at least 30%. While the main focus of osteoarthritis research has been on treating damage to the cartilage, osteoarthritis will also lead to damage to the adjacent trabecular bone due to wear via shearing down of the tissue’s surface. Considering this, in conjuncture with transplanted cartilages’ inability to integrate into the native tissue, unlike the surrounding bone, the significance of a combined osteochondral …

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 …

Development Of New, Diverse Triggering Mechanisms Of Shape Memory Polymers For Cell Mechanobiology Studies, Mark Macios

Theses - ALL

Over the past decade, several shape-memory polymer (SMP) substrates capable of changing topography under cell-culture conditions have been developed for the study of cell mechanobiology. Most initial reports of cytocompatible SMP platforms employed thermal triggering under ambient heating conditions, which, especially in hydrated environments, is a slow process that generally takes several minutes to a few hours. Also, biocompatible SMPs initially featured recovery temperatures too high for cells to maintain viability during the thermal trigger. To overcome the limitations of ambient thermal heating triggered shape recovery, the goal of this thesis was to develop new cytocompatible SMPs that can trigger …

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 …

Investigation Of Human Adipose-Derived Stem-Cell Behavior Using A Cell-Instructive Polydopamine-Coated Gelatin-Alginate Hydrogel., Settimio Pacelli, Aparna R Chakravarti, Saman Modaresi, Siddharth Subham, Kyley Burkey, Cecilia Kurlbaum, Madeline Fang, Christopher A Neal, Adam J Mellott, Aishik Chakraborty, Arghya Paul

Chemical and Biochemical Engineering Publications

Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)-treatment as a binding platform for bioactive compounds to create a versatile gelatin-alginate (Gel-Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose-derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro-angiogenic peptide (QK). The pDA treatment efficiently retained …

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 …

Understanding And Improving Adult Stem Cells For Cartilage Tissue Engineering, Dakota Katz

McKelvey School of Engineering Graduate Student Theses & Dissertations

Articular cartilage allows for near frictionless joint movement; however, when damaged the tissue has very little capacity for self-repair. Tissue engineering can be used to both repair damaged articular cartilage and as an in vitro model for joint disease. Commonly used cell sources for tissue engineering are adipose-derived and bone marrow-derived mesenchymal stem cells (ASCs and MSCs) because they can be patient matched, expand rapidly in culture, and have multipotent differentiation potential. However, donor-to-donor variability of differentiation potential can mask the results of in vitro experiments and ASCs and MSCs only retain their multipotency for a limited number of passages. …

Engineering Nucleus Pulposus Cell-Matrix Interactions With Laminin Ligands For Tissue Regeneration, Julie Elizabeth Speer

McKelvey School of Engineering Graduate Student Theses & Dissertations

Low back pain and degenerative conditions of the intervertebral disc (IVD) represent major global socioeconomic and medical burdens. The structures that comprise the IVD including the anulus fibrosis and the nucleus pulposus (NP) work together to stabilize the axial skeleton and distribute mechanical forces. However, the degenerative cascade, which is thought to begin with changes to the NP, results in alterations to the disc that can be seen across length scales including elongated cell shapes, tissue dehydration, and loss of disc height. Patients who present clinically with these changes may also experience altered biomechanics, pain upon motion, impairments to their …

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 …

Manipulation And Patterning Of Mammalian Cells Using Vibrations And Acoustic Forces, Joel Cooper

USF Tampa Graduate Theses and Dissertations

Recently, there has been a surge in researchers and scientists investigating different methods which move, manipulate, and pattern biological cells. Multiple different mechanisms can be used for cellular manipulation, microfluidics, biochemical queues, and even optics, just to name a few. However, all techniques have their downsides. A majority of these methods require expensive equipment or reagents and can only manipulate a small number of cells at a time.

Some of the most common cell manipulation devices utilize acoustic pressure waves to move the cells to desired locations. Currently, it is unknown what level of force from these types of devices …

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 …

In Vitro Atherosclerosis Disease Model Via The Ring Stacking Method, Cameron Brandon Pinnock

Wayne State University Dissertations

Creation of an in vitro atherosclerotic disease model using the novel Ring Stacking Method. Singular self-assembling tissue rings made up smooth muscle cells and fibrin hydrogel are stacked on one another to create a tissue engineered vessel. These biologically engineered blood vessels are then seeded with endothelial cells via combined static rotational and dynamic bioreactor in order to create a functional intima layer. Early stage atherosclerosis was induced via the addition of oxidized low-density lipoproteins (ox-LDL) to the fibrin hydrogel that creates the media layer of the engineered vessel. After the creation of the intima layer the engineered vessel was …