Biomedical Engineering and Bioengineering Commons^™

In Vitro And In Vivo Diabetic Models For Assessment Of Tissue Engineered Vascular Grafts, Juan Carlos Carrillo Garcia

All Dissertations

Diabetes has become one of the leading causes of lower-limb loss worldwide. Every 30 seconds, a person loses a limb due to diabetic-related vascular complications. About one-third of patients needing lower-limb bypass surgery have debilitated autologous vessels unsuitable for use, and no other good long-term options are available. These detrimental effects on the vasculature are caused mainly by the hyperglycemic and hyperlipidemic conditions derived from diabetes. Under these conditions, an increase in advanced glycation end products (AGEs) and reactive oxygen species leads to irreversible crosslinks of extracellular matrix proteins, accelerating vascular pathology through vascular stiffening, endothelial dysfunction, inflammation, atherosclerosis, fibrosis, …

Development Of A Cell-Based Regenerative Strategy To Modulate Angiogenesis And Inflammation In Ischemic Muscle, Fiona E. Serack

Electronic Thesis and Dissertation Repository

The delivery of human adipose-derived stromal cells (hASCs) to ischemic tissues represents a promising strategy to promote vascular regeneration for patients with critical limb ischemia (CLI). This thesis focused on the evaluation of hydrogels to enhance the retention and pro-angiogenic capacity of hASCs following delivery in vivo. Additionally, priming strategies to augment the paracrine function of hASCs were developed and assessed.

Recognizing the importance of endogenous macrophages in the pro-regenerative function of hASCs, delivery using a previously-developed hydrogel system, composed of peptide-functionalized methacrylated glycol chitosan (MGC-RGD) and a copolymer of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG(PTMC-A)₂), was …

Investigation Of Dynamic Culture On Matrix-Derived Microcarriers As A Strategy To Modulate The Pro-Regenerative Phenotype Of Human Adipose-Derived Stromal Cells, Mckenna R. Tosh

Electronic Thesis and Dissertation Repository

Pre-conditioning of adipose-derived stromal cells (ASCs) by tuning the cellular microenvironment during expansion has the potential to modulate their pro-regenerative functionality. The current study investigated the effects of microcarrier composition (decellularized adipose tissue versus collagen), oxygen tension (2% versus ~20% O₂) and stirring rate (static, 20, 40 rpm) on human ASCs cultured within spinner flask bioreactors. Dynamic culturing under 20% O₂ resulted in more consistent cell growth on both microcarrier substrates, leading to increases in microcarrier contraction and stiffness. Culturing on the microcarriers modulated the hASC immunophenotype, with varying CD90 and CD26 expression levels observed under the …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

A Novel Electroconductive Nanofibrous Scaffold For Bone Regeneration, Mitchell Kenter

Medical Engineering Theses

The goal of this study was to develop a biodegradable and conductive scaffold to mimic the piezoelectric properties of bone and the architecture of the extracellular matrix. Poly(3,4- ethylenedioxythiophene) (PEDOT) is a conductive polymer of great interest in tissue engineering due to excellent electrical stability and biocompatibility. To enhance its conductivity, dopants such as dimethyl sulfoxide (DMSO) can be added. Engineered graphene oxide (GO) can also be introduced as oxidant to enhance conductivity and mechanical properties. PEDOT nanocomposites were synthesized by oxidative polymerization of 3, 4-Etylenedioxythiophene monomer (EDOT) in the presence of GO, DMSO, ferric chloride and various solvents. The …

Characterizing Mechanical Regulation Of Bone Metastatic Breast Cancer Cells, Boyuan Liu

Doctoral Dissertations

Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical stimuli in the skeleton are an important microenvironmental parameter that modulates tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. This work focused on bone matrix deformation and interstitial fluid flow based on their well-known roles in bone remodeling and in primary breast cancer. The goal of our research was to establish a platform that could define the relationship between …

Characterization Of Tissue-Specific Matrix-Derived Bioscaffolds For Nucleus Pulposus Cell Culture, Marco A. Herrera Quijano

Electronic Thesis and Dissertation Repository

Bioscaffolds derived from the extracellular matrix (ECM) have shown the capacity to promote regeneration by providing tissue-specific biological instructive cues that can enhance cell survival and direct lineage-specific differentiation. This study focused on the development and characterization of two-dimensional (2-D) and three-dimensional (3-D) cell culture platforms incorporating decellularized nucleus pulposus (DNP). First, a novel detergent-free protocol was developed for decellularizing bovine NP tissues that was effective at removing cellular content while preserving key ECM constituents including collagens and glycosaminoglycans. Culture studies showed that 2-D coatings derived from the DNP could support cell attachment but did not maintain or rescue the …

Synthesis And Performance Testing Of Ecm Fiber Scaffolds, Cassandra Reed

Graduate Theses and Dissertations

The progression of regenerative medicine has advanced the treatment of multiple illnesses and injuries throughout the years. A good example of the benefits of this research is the work that has gone into volumetric muscle loss (VML), where more than 20% of the muscle is loss. Skeletal muscle makes up 40% of the human body so a loss of that size greatly diminishes the strength, the flexibility, physiology, and quality of life of the injured individual. For that reason, various techniques are used to counteract the loss of structure and innate cellular signaling in order to circumvent that from happening. …

Evaluating The Effects Of Wood Source On The Physicochemical Properties Of Crosslinked Cellulose Nanocrystals, Helena Tchoungang Nkeumen

Graduate Theses and Dissertations

Cellulose is an abundant and naturally occurring biopolymer that has been used by humans for food, shelter, and clothing for about two centuries now. Highly crystalline nanoparticles derived from cellulose, called cellulose nanocrystals (CNCs), show great potential to meet the rising need for sustainable and nontoxic materials for biomedical applications. However, multiple biomedical applications of CNCs, such as those involving their use in tissue engineering scaffolds, require CNC-based structures to be stable in aqueous environments, a property that native CNCs do not possess due to their inherent hydrophilicity. Chemical crosslinking of CNCs addresses this issue by providing aqueous stability to …

Extracellular Matrix-Derived Modular Bioscaffolds For Soft Connective Tissue Regeneration, Pascal Morissette Martin

Electronic Thesis and Dissertation Repository

Human decellularized adipose tissue (DAT) represents a promising extracellular matrix (ECM) source for the development of biomaterials, with its properties conductive of angiogenesis, adipogenesis, and scaffold remodelling. This thesis sought to provide new fundamental insight into the design of ECM-derived bioscaffolds by developing novel modular biomaterials for soft connective tissue regeneration and by studying the effects of ECM composition on cell function and fate.

Initial studies explored the effects of ECM composition of pre-assembled bead foams derived from DAT or commercially-sourced bovine collagen (COL) on human wound edge dermal fibroblasts (weDFs) sourced from chronic wounds. In vitro testing under conditions …

The Co-Delivery Of Syngeneic Adipose-Derived Stromal Cells And Macrophages On Decellularized Adipose Tissue Bioscaffolds For In Vivo Soft Tissue Regeneration, Hisham A. Kamoun

Electronic Thesis and Dissertation Repository

Decellularized adipose tissue (DAT) bioscaffolds are a promising platform for the delivery of pro-regenerative cell populations with the goal of promoting adipose tissue regeneration. The current study investigated the effects of seeding DAT bioscaffolds with syngeneic bone marrow-derived macrophages and/or adipose-derived stromal cells (ASCs) on in vivo soft tissue regeneration. Methods were established to derive the macrophages from MacGreen mice, which were dynamically seeded onto the DAT scaffolds alone or in combination with ASCs. Seeded and unseeded scaffolds were implanted subcutaneously into C57Bl/6 mice. At 2 and 4 weeks, cell infiltration, angiogenesis, and adipogenesis were analyzed through histology and immunohistochemistry. …

Controlling Strain Energy Density In 3d Cellular Collagen Constructs During Complex Loads, Katherine Hollar

Boise State University Theses and Dissertations

Mechanical stimulation applied to damaged soft tissues, such as ligament, can promote tissue remodeling to accelerate healing. To help identify treatments that encourage ligament healing, bioreactors have been designed to subject 3D cellularized constructs to various loading conditions in order to determine the mechanical mechanisms that trigger cell-mediated repair. An innovative approach is to use a bioreactor to apply controlled states of biaxial stress to study the effects of strain energy density and distortion energy on cell activity. Tissue distortion has been linked to changes in the structure and function of ligament, yet the specific impact of distortion energy on …

Investigation Of The Effect Of Age On Regenerative Outcomes Following Treatment Of Volumetric Muscle Loss Injuries, John Taehwan Kim

Graduate Theses and Dissertations

Volumetric muscle loss (VML) is a traumatic injury in skeletal muscle resulting in the bulk loss of more than 20% of the muscle’s volume. Included in the bulk loss of muscle is the skeletal muscle niche comprised of nerve bundles, vasculature, local progenitor cells, basal lamina, and muscle fibers, overwhelming innate repair mechanisms. The hallmark of VML injury is the excessive accumulation of non-contractile, fibrotic tissue and permanent functional deficits. Though predominant in the younger demographic, the elderly population is also captured within VML injuries. There are many factors that change with aging in skeletal muscle that may further hinder …

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Graduate Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation …

Fabrication And Characterization Of Collagen-Polypyrrole Constructs Using Direct-Ink Write Additive Manufacturing, Rooshan Arshad

Electronic Thesis and Dissertation Repository

Current efforts in the tissue engineering field are being directed towards the creation of platforms which will facilitate in instructing cells towards biologically relevant outcomes such as stem cell differentiation and disease pathophysiology. Traditional fabrication methods serve as a limiting factor for the production of such platforms as they lack feature and geometric complexity. Additive Manufacturing (AM) offers advantage over said methods by affording designers creative freedom and great control over printed constructs. Such constructs can then be used to create appropriate models for study- ing a plethora of tissues and structures. An AM methodology for Direct-Ink Write (DIW) printing …

Design And Mechanical Characterization Of 3d Printed Gradient Porosity Poly(Propylene Fumarate) Scaffolds, Andrea Felicelli

Williams Honors College, Honors Research Projects

Worldwide incidence of bone disorders and conditions, an already prevalent problem, is expected to double by 2020 from the rate in 2013 due to factors such as higher life expectancies and lower levels of physical activity. Every year in the United States, over half a million patients receive bone defect repairs, with costs greater than $2.5 billion. Current repairs are typically done with bone grafts, which are often costly and can result in added complications in the donor surgical site. Tissue engineering, a growing field that seeks to assist and enhance tissue defect repairs through the use of synthetic materials, …

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

Molded Features In Pdms For Fabricating Bacterial Cellulose For Various Geometries, Mitchell Habegger

Williams Honors College, Honors Research Projects

The purpose of producing features on bacterial cellulose (BC) is to facilitate the elongation and alignment for cells, in this case Normal Human Dermal Fibroblast (NHDF) cells. The elongated cells have applications in wound healing, tissue engineering, disease diagnostics, and many other fields. Experiments were run to test the effectiveness of transferring features to BC sheets from features induced by fracturing on polydimethylsiloxane (PDMS) and those duplicated from molds with existing features. The features were duplicated to BC sheets by either air drying or Guided Assembly-Based Biolithography (GAB). The research results showed that fracture inducing on PDMS produced very small …

Syngenic Adipose-Derived Stem/Stromal Cells Delivered In Decellularized Adipose Tissue Scaffolds Enhance In Vivo Tissue Regeneration Through Host Cell Recruitment, Kevin P. Robb

Electronic Thesis and Dissertation Repository

Decellularized adipose tissue (DAT) represents a promising adipogenic bioscaffold for applications in soft tissue augmentation or reconstruction. With the goal of investigating the role of syngeneic donor adipose-derived stem/stromal cells (ASCs) and host myeloid cells during in vivo adipose tissue regeneration, transgenic reporter mouse strains were used to track these cell populations within ASC-seeded and unseeded DAT scaffolds. Donor ASCs were obtained from dsRed transgenic mice. These cells were shown to express characteristic cell surface markers, and multilineage differentiation capacity was confirmed. To facilitate cell tracking, DAT scaffolds were subcutaneously implanted into MacGreen mice in which myeloid cells express enhanced …

Effects Of Uniaxial Cyclic Strain On Endothelial Progenitor Cells, Maria Alejandra Zeballos Castro

Biomedical Engineering Undergraduate Honors Theses

Despite the high prevalence of calcific aortic valve disease (CAVD), the underlying mechanisms of pathogenesis have not been found yet. Therefore, it is extremely important to study CAVD and understand how it develops. For this matter, we decided to study the potential of endothelial progenitor cells (EPCs) for use in tissue-engineered models of heart valves. EPCs were chosen as the cell source of interest for this study due to their high neovascularization potential and use in regenerative medicine and cardiovascular tissue engineering.

In this project, we aimed to engineer the microenvironment of cells that are involved in the formation of …

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 …

Developing Afm Techniques For Testing Peg Hydrogels, Hannah L. Cebull, Jessica Stukel, Rebecca Willits

Williams Honors College, Honors Research Projects

Many instruments are used to find elastic properties of biological samples using methods such as tensile and bending tests, but using the atomic force microscope (AFM) is considered a non-destructive method because it can provide repeated local stiffness information without damaging the sample. It additionally allows the sample to be tested in an aqueous environment, which is optimal for soft materials such as hydrogels. The nanoindentation is performed via cantilever, measuring the deflection of the cantilever during the contact of the sample using a laser. Compared to hard samples, testing soft materials can present more challenges when working with the …

Biodegradable Nano-Hybrid Polymer Composite Networks For Regulating Cellular Behavior, Charles Henley Sprague

Masters Theses

Photo-crosslinkable polymeric biomaterials have emerged in the field of biomedical research to promote tissue regeneration. For example, scaffolds that can be crosslinked and hardened in situ have been known to make suitable implant alternatives. Since injectable and photo-crosslinkable biomaterials offer the advantage of being minimally invasive, they have emerged to compete with autografts, a current highly invasive method to repair diseased tissue. A series of novel photo-crosslinkable, injectable, and biodegradable nano-hybrid polymers consisting of poly(ε-caprolactone fumarate) (PCLF) and polyhedral oligomeric silsesquioxane (POSS) has been synthesized in our laboratory via polycondensation. To engineer the material properties of the nano-hybrid networks, varied …

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 …

Sol-Gel Derived Biodegradable And Bioactive Organic-Inorganic Hybrid Biomaterials For Bone Tissue Engineering, Bedilu A. Allo

Electronic Thesis and Dissertation Repository

Treatments of bone injuries and defects have been largely centered on replacing the lost bone with tissues of allogeneic or xenogeneic sources as well as synthetic bone substitutes, which in all lead to limited degree of structural and functional recovery. As a result, tissue engineering has emerged as a viable technology to regenerate the structures and therefore recover the functions of bone tissue rather than replacement alone. Hence, the current strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate and function.

In this …

Design Of Experimentation To Systematically Determine The Interaction Between Electrospinning Variables And To Optimize The Fiber Diameter Of Electrospun Poly (D, L-Lactide-Co-Glycolide) Scaffolds For Tissue Engineered Constructs, Yvette S. Castillo

Master's Theses

Cardiac disease causes approximately a third of the deaths in the United States. Furthermore, most of these deaths are due to a condition termed atherosclerosis, which is a buildup of plaque in the coronary arteries, leading to occlusion of normal blood flow to the cardiac muscle. Among the methods to treat the condition, stents are devices that are used to restore normal blood flow in the atherosclerotic arteries. Before advancement can be made to these devices and changes can be tested in live models, a reliable testing method that mimics the environment of the native blood vessel is needed. Dr. …

Co-Culture Of Smooth Muscle Cells And Endothelial Cells On Porous 3d Polyurethane Scaffolds For Vascular Tissue Engineering, Aparna Bhattacharyya

Electronic Thesis and Dissertation Repository

One of the challenges in the designing of clinically-relevant vascular substitutes is our lack of understanding on how vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) interact in the graft. The aim of this study was to examine the factors that play a role in VSMC and VEC interaction in 3D co-culture. Highly porous 3D poly(carbonate urethane) scaffolds were fabricated using a solvent casting and particulate leaching method. VSMCs and VECs were co-cultured for 48 hours. Immunofluorescence staining showed that VSMCs readily attached to the scaffold and formed dense confluent layers which facilitated the organization of VECs of …

Evaluation Of Decellularization Procedures For Porcine Arteries, Charles Clapp

Biomedical Engineering

Coronary artery disease has become the leading cause of death in the United States, with over 425,000 deaths in 2006. Stenting has evolved into the preferred preventative technique for myocardial infarction by opening up an occluded artery, due to its low invasiveness compared to the alternative of coronary artery bypass grafting. Bare metal stents have been improved by coating with anti-proliferative drugs to advance their effects, but even drug eluting stents still have a risk of restenosis, thrombus formation, and necessary revascularization. Continual advancement in stent design necessitates faster, effective pre-clinical evaluation techniques. Kristen Cardinal, Ph.D., developed the blood vessel …

A Novel In-House Design Of A Bioreactor For The Modeling Of An In Vitro Blood Brain Barrier Model, Ian Mahaffey

Biomedical Engineering

The blood brain barrier is the protector of the central nervous system and a physical barrier that functions to regulate the substances that can pass in and out of the brain; it is the function and integrity of this system that keeps the homeostasis of the central nervous system. Yet this shield against foreign invaders in the blood also prevents drugs designed for treatment of various ailments of the central nervous system from reaching their target in the brain. Developing drugs that can pass through this barrier, and understanding it’s function has become an area of increasing interest. Many researchers …

Development Of An In-Vitro Hyperglycemic Tissue Engineered Blood Vessel Mimic, Brian C. Wong

Biomedical Engineering

No abstract provided.