Biomaterials Commons^™

Decellularization Of Porcine Cartilage Promotes Chondrogenic Differentiation Of Human Chondrocytes, Roxanne Nicole Stone

Boise State University Theses and Dissertations

Knee osteoarthritis (knee OA) is the most common type of osteoarthritis (OA) and accounts for 70% of arthritis-related hospital admissions and 23% of clinical visits. Major limitations in both the current non-surgical and surgical methods are that they only relieve pain and show no evidence for restoring natural tissue anatomy. Leaders in the field propose that a stem cell treatment approach holds promise for the regeneration of a greater proportion of hyaline-like tissue at the repair site. (Cross et al., 2014; Escobar Ivirico, Bhattacharjee, Kuyinu, Nair, & Laurencin, 2017; Helmick et al., 2008; Toh, Foldager, Pei, & Hui, 2014).

It …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal …

Hydrolytic Degradation Study Of Polyphosphazene-Plga Blends, Riley Blumenfield

Honors Scholar Theses

The synthesis and in vitro degradation analysis of thin films of poly[(glycineethylglycinato)₇₅(phenylphenoxy)₂₅phosphazene]
(PNGEG₇₅PhPh₂₅) and poly[(ethylphenylalanato)₂₅(glycine-
ethylglycinato)₇₅phosphazene] (PNEPA₂₅GEG₇₅) blended with poly(lactic-co-glycolic acid) (PLGA) was conducted to determine the blends’ potential for use as scaffolding materials for tissue regeneration applications. The samples were synthesized with glycylglycine ethyl ester (GEG) acting as the primary substituent side group, with cosubstitution by phenylphenol (PhPh) and phenylalanine ethyl ester (EPA) to make the final product [1]. Blends of 25% polyphosphazene, 75% PLGA and 50% polyphosphazene, 50% PLGA were …

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 …

Production And Purification Of Basic Fibroblast Growth Factor Fused To Two Collagen Binding Domains Expressed In E. Coli Bl21 Using Flask And Fed-Batch, Hazim Aljewari

Graduate Theses and Dissertations

Delivering effective and non-toxic doses of bioactive materials that can aid in activating tissue regeneration to wounded tissue has proven to be an enormous challenge. This study was designed to produce a potential therapeutic recombinant protein by fusing two collagen binding domains to basic fibroblast growth factors (bFGF) through a collagenase cleavage site linker, so it can release the bFGF in a wound site by the action of this enzyme. The novel fusion protein was expressed in Escherichia coli BL-21 (E. coli) using traditional flask shaker and fed-batch cultivation. Cell lysate was purified by FPLC using Immobilized metal affinity chromatography …

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 …

Nano Fab Lab 63, Brian K. Deemer, Josh Clemons, Nick Brodine, Delaney Fitzsimmons

Mechanical Engineering

Lawrence Livermore National Laboratories (LLNL) has several steps in the production process for ceramic nanofiber tubes that they would like to improve - electrospinning, cutting, rolling, sealing and heat treating. We undertook the challenge to deliver LLNL with a semi-automated process that efficiently integrates the steps of cutting, rolling, and sealing to save time and improve control over end dimensions. In this document, we discuss the technical background of the manufacturing steps currently followed to create nanofiber tubes, identify which steps are incorporated in our prototype and explain how they will interface with one another, define the design requirements, present …

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 …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Investigating Virus Clearance Via Ph Inactivation During Biomanufacturing, Wenbo Xu

Biomedical Engineering Undergraduate Honors Theses

In the processing of biopharmaceuticals, viral clearance and viral safety are important for the development of monoclonal antibodies. Murine xenotropic leukemia virus (XMuLV) is one of the retroviruses, recommended by Food and Drug Administration (FDA) as a model virus for viral clearance via inactivation from therapeutics derived from Chinese hamster ovary cells (CHO). A robust and effective method was investigated to clear or inactivate endogenous viruses by low pH inactivation. The effects of different conductivity and inactivated time on XMuLV clearance was determined. Acetate buffer was prepared with different conductivity, and 2% XMuLV was spiked into acetate buffer. XMuLV virus …

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …

Modification Of Lipid Microenvironments On Solid Support Structures For Use In Transmembrane Protein Assays, William J. Houlihan

Dissertations and Theses

Gamma-Secretase (γ-secretase) is a transmembrane protease of increasing interest, which has been shown to have significant connections to both cancer and Alzheimer’s disease. γ-secretase cleaves both Notch-1, a transmembrane signaling protein, and Amyloid precursor protein (APP), a transmembrane protein whose cleavage may result in the formation of β-amyloid plaques in the brain. Notch-1 and APP are widely studied proteins that have substantial impacts on the development and proliferation of cancer and Alzheimer’s disease, respectively. Notch-1 partakes in the signaling of apoptosis in damaged and mutated cells, thus its cleavage by γ-secretase within the plasma membrane has ramifications on cell growth …

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, …

The Production And Characterization Of Chitosan Based Microgels Using A Novel Microfluidic Device To Promote Cell Survival, Kaileen Shevchuk

Williams Honors College, Honors Research Projects

The purpose of this project is to synthesize and characterize perfluorocarbon modified methacrylamide chitosan (MACF) microgels produced with the use of a capillary-based microfluidic device. Since cell survival and development is highly related to particles physical properties, analysis of microgels set out to determine the particle’s physical properties. I hypothesize that the viscosity of the MACF polymer as well as the amount of photo initiator influence the physical properties of synthesized particles and as a result can generate particles with various features for cell culture in terms of shape, size, charge and swelling abilities. This hypothesis was validated through the …

Cell Surface Coatings For Mammalian Cell-Based Therapeutic Delivery, Pei-Jung Wu

Theses and Dissertations--Chemical and Materials Engineering

The cell plasma membrane is an interactive interface playing an important role in regulating cell-to-cell, cell-to-tissue contact, and cell-to-environment responses. This environment-responsive phospholipid layer consisting of multiple dynamically balanced macromolecules, such as membrane proteins, carbohydrate and lipids, is regarded as a promising platform for various surface engineering strategies. Through different chemical modification routes, we are able to incorporate various artificial materials into the cell surface for biomedical applications in small molecule and cellular therapeutics.

In this dissertation, we establish two different cell coating techniques for applications of cell-mediated drug delivery and the localization of cell-based therapies to specific tissues. The …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

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 …

An Engineer’S Take On The Bone-Ligament Interface: Utilizing Novel Technology To Improve Clinical Outcomes, Emma Garcia

Shared Knowledge Conference

Ligament repair is a common surgical practice with a significant lack of viable replacements. The current gold standard for repair is the use of tendon grafts from cadavers or from another place in the patient’s body; however, these often cause more problems than they solve including immune responses or a lack of mobility in another place in the body. Synthetic replacements are of growing interest, though the ability to mimic the complex structure of the ligament and how it connects to the bone remains an obstacle. Our lab built a 3D bioprinter combined with an electrospinner to address this complicated …

Hyperspectral Imaging For Characterizing Single Plasmonic Nanostructure And Single-Cell Analysis, Nishir Sanatkumar Mehta

LSU Master's Theses

Orientation of plasmonic nanostructures is an important feature in many nanoscale applications such as photovoltaics, catalyst, biosensors DNA interactions, protein detections, hotspot of surface-enhanced Raman spectroscopy (SERS), and fluorescence resonant energy transfer (FRET) experiments. Silver nanocubes with significant spectral signatures between 400-700 nm are observed in this experimental research. Whereas study of single cells will enable the analysis of cell-to-cell variations within a heterogeneous population. These variations are important for further analysis and understanding of disease propagation, drug development, stem cell differentiation, embryos development, and how cells respond to each other and their environment. Adipose-derived mesenchymal stem cells possess the …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline Alexandria De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Soft-Microrobotics: The Manipulation Of Alginate Artificial Cells, Samuel Sheckman

Mechanical Engineering Research Theses and Dissertations

In this work, the approach to the manipulation of alginate artificial cell soft-microrobots, both individually and in swarms is shown. Fabrication of these artificial cells were completed through centrifugation, producing large volumes of artificial cells, encapsulated with superparamagnetic iron oxide nanoparticles; these artificial cells can be then externally stimulated by an applied magnetic field. The construction of a Permeant Magnet Stage (PMS) was produced to manipulate the artificial cells individually and in swarms. The stage functionalizes the permanent magnet in the 2D xy-plane. Once the PMS was completed, Parallel self-assembly (Object Particle Computation) using swarms of artificial cells in complex …

Analysis Of Biological Response To Ecm Hydrogel Injection, Grady Dunlap

Biomedical Engineering Undergraduate Honors Theses

Abstract

Under normal circumstances, skeletal muscle possesses the capacity to regenerate and heal via inflammatory and myogenic pathways. In cases of severe tissue loss or certain diseases, this capacity is lost, often resulting in loss of tissue function. Extracellular matrix (ECM), the protein scaffold which houses cells in physiological tissue, has been shown to have structural and chemical properties which influence cell migration and phenotype. This results in ECM’s capacity to encourage a regenerative response when implanted into severely damaged skeletal muscle. Additional advantages are apparent when an ECM scaffold is digested into a hydrogel, namely less invasive implantation via …

Designing Synthetic Environments To Control Valvular Interstital Cells In Vitro, Kent E. Coombs

Biomedical Sciences ETDs

Aortic valve disease (AVD) is a large contributor to health costs in the United States affecting 2.8% of the population greater than 75 years old. With a growing elderly population due to medical advances, AVD will continue to rise in prevalence over time. Current treatments for AVD are insufficient due to a lack of preventative therapies and the bioprosthetic valves used for surgical replacement have major limitations. Tissue engineered heart valves (TEHVs) present an ideal solution to current AVD needs because of their biocompatibility, capability to integrate with the host’s tissue, and ability to utilize the natural repair mechanisms of …

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, …

Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers

Theses and Dissertations

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages …