Molecular, Cellular, and Tissue Engineering Commons^™

Quantifying The Effect Of Intrinsic Aging On Skin Microstructure And Mechanical Function Using Multiphoton Microscopy, Alan Edward Woessner

Graduate Theses and Dissertations

Over the next couple of decades, the number of elderly individuals is expected to double, bringing increased healthcare spending due to seemingly minor injuries to skin. In skin, the 3D dermal collagen fiber network, which is the primary load-bearing structure, undergoes changes in organization and composition due to intrinsic aging. However, the relationships between altered microstructure and mechanical function is not well understood. Quantitative imaging techniques have been used in the past to link skin structure to mechanical function, but previous analysis has been limited to 2D assessments. Multiphoton microscopy (MPM) is a non-destructive imaging technique with intrinsic depth-sectioning capabilities, …

3d Printable And Computational Models Of The Bone Marrow Mechanical Environment, Alexander Regner

Boise State University Theses and Dissertations

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in part regulated by mesenchymal stem cells (MSCs). We reported that daily low intensity vibration (LIV) restores MSC proliferation in senescence and simulated microgravity models, suggesting reduced mechanical signal delivery to MSCs likely contributes to declining bone mechanoresponse. To this end, we have developed a 3D bone marrow analog which controls trabecular geometry, marrow mechanics and external stimuli.

Finite element (FE) models of hydrogels, representing bone marrow, were generated using instantaneous compression (1000% strain/s, 20% strain) and relaxation experiments (100s) of both gelatin and hyaluronin-based hydrogels. …

Oxone® Mediated Tempo-Oxidized Cellulose Nanomaterials: Material Characterization, Ultrafiltration Membrane Separations, And Thin Film Composite Gas Transport Analysis, John Phillips Moore

Graduate Theses and Dissertations

Cellulose nanomaterials (CNMs) are derived from plant matter and are comprised of nanoscopic cellulose crystals and fibers. They have a diverse set of applications, from cosmetics to oil recovery. This study focuses on the properties of Oxone® mediated TEMPO-oxidized cellulose nanomaterials (OTO-CNMs) and their use in controlling the transport properties of polymeric substrates. Synthesis and characterization of cellulosic nanoparticles have resulted in the creation of OTO-CNMs with properties that increase hydrophilicity. With added hydrophilicity, OTO-CNMs possess lower fouling propensity, making them ideal membrane additive for transport limited separations such as hemodialysis.

To utilize the material and unique properties thereof, this …

Analyzing The Effects Of E-Hook Peptides On Kinesin-1, Ashton Ward Murrah, Baylee Hope Howard

Honors Theses

Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.

The goal of this study is to develop a method to prevent …

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 …

Highly Branched Polymers Based On Poly(Amino Acid)S For Biomedical Application, Marisa Thompson, Carmen Scholz

PRC-Affiliated Research

Polymers consisting of amino acid building blocks continue to receive consideration for biomedical applications. Since poly(amino acid)s are built from natural amino acids, the same building blocks proteins are made of, they are biocompatible, biodegradable and their degradation products are metabolizable. Some amino acids display a unique asymmetrical AB2 structure, which facilitates their ability to form branched structures. This review compares the three forms of highly branched polymeric structures: structurally highly organized dendrimers, dendrigrafts and the less organized, but readily synthesizable hyperbranched polymers. Their syntheses are reviewed and compared, methods of synthesis modulations are considered and variations on their traditional …

Highly Branched Polymers Based On Poly(Amino Acid)S For Biomedical Application, Marisa Thompson, Carmen Scholz

PRC-Affiliated Research

Polymers consisting of amino acid building blocks continue to receive consideration for biomedical applications. Since poly(amino acid)s are built from natural amino acids, the same building blocks proteins are made of, they are biocompatible, biodegradable and their degradation products are metabolizable. Some amino acids display a unique asymmetrical AB2 structure, which facilitates their ability to form branched structures. This review compares the three forms of highly branched polymeric structures: structurally highly organized dendrimers, dendrigrafts and the less organized, but readily synthesizable hyperbranched polymers. Their syntheses are reviewed and compared, methods of synthesis modulations are considered and variations on their traditional …

Project Alien, Rebecca Mccallin, Madelyn Hoying, Alex Evans, Matthew Nestler, Karli Rae Sutton, Garett Craig, Lucia Secaia Del Cid, Alexander Guy, Rachel Fernandez, Amanda Trusiak, Paige Aley, Ingabire Gakwerere, Nina Dorfner, Maria Mosbacher, Mary Flavin, Selvin Hernandez, Audrey Steen, Benjamin Kazimer

Undergraduate Research and Scholarship Symposium

Project ALIEN is a comprehensive plan to send humans to Mars to look for life on the Martian surface while exploring the viability and adaptability of terrestrial microbes in Martian atmospheric conditions. ALIEN will use a ballistic capture trajectory to get to Mars and stay in aerostationary orbit for a 30-day surface mission, during which two surface crewmembers will perform a variety of experiments to achieve the mission’s goals of Martian microbial discovery within brines of the Gale Crater and terrestrial microbe adaptability and viability to Martian conditions. Experimentation is based on the presumption that Martian microbes are metabolically similar …

Tissue Engineering Pre-Reads, Ryan M. Williams

Open Educational Resources

This material provides an introduction to a tissue engineering module in an experimental methods in biomedical engineering course. Students are expected to be familiar with this material prior to a pre-assessment taken at the beginning of class as we have condense lecture time this semester.

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

Master's Theses

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

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

Master's Theses

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

Multifactorial Media Analysis Via Design Of Experiment For Type Ii Collagen In Primary Rabbit Chondrocytes, Javier A. Velez Toro

Honors Undergraduate Theses

Osteoarthritis is a prevalent disease that affects the articular cartilage of the joints. Millions of people suffer worldwide and it is a major cause of disability in the United States. Current research for treatments of osteoarthritis are studying tissue-engineered cartilage in vitro generated by articular chondrocytes. A challenge faced in vitro for cartilage tissue engineering is the failure of chondrocytes to produce adequate expression of type II collagen. Surprisingly, the media commonly used in vitro lacks 14 vitamins and minerals present in the physiological environment of chondrocytes. Therefore, studying the interactions between micronutrients and chondrocytes may help in potentially increasing …

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence M. Donohue Jr., Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes

Nebraska Center for Biotechnology: Faculty and Staff Publications

Abstract Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

Biomechanical Investigation Of Plant Vascular Tissue For Bio-Inspired Design And Flexible Composites, Mukesh Roy

Electronic Theses and Dissertations

Since the inception of evolution, nature has continuously optimized all the natural materials. These optimizations are so efficient that scientists and engineers have started taking inspiration from nature. Such inspiration-based solutions provide sustainable development of new materials with enhanced structural properties and functionalities (such as stiffness, stability, toughness, self-healing etc.). This variety of properties and functionalities is mainly due to the hierarchical organization of such components. Abstraction of the hidden cues of the hierarchical organization, principles and underlying structure-function relations are some of the critical approaches of bioinspired materials design. Inspiration from animals and plants has helped develop the design …

Injectable Gelatin-Silk Fibroin Composite Hydrogels For In Situ Cell Encapsulation, Ryann D. Boudreau

Honors Theses and Capstones

Hydrogels are widely used tools for tissue engineering and regenerative medicine. Characterized as biofunctional, water-based polymer matrices with tunable mechanical properties, hydrogels have promising but limited applications in biomedical engineering, due to poor and static matrix strength. Here we plan to rectify this issue by introducing a new hydrogel made from a composite of gelatin and silk fibroin crosslinked by microbial transglutaminase (mTG) instantly and beta sheet formation gradually, respectively. This interpenetrating network (IPN) shows enhanced mechanical stiffness and strength compared to gelatin hydrogels, and is capable of encapsulating human cells with high viability demonstrated by the encapsulation of human …

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 …

Quantifying Mafenide Release From 3d Printed Phenylalanine-Coumarin Copolyester Scaffolds, Jacob Seeh

Williams Honors College, Honors Research Projects

This project addressed burn wound healing through controlled release of the antibacterial drug mafenide encapsulated by a copolyster into 3D printed scaffolds. Scaffolds were printed at 25^oC and 0.77-1 bar in a cross-hatch pattern with uniform thickness, distance between parallel layers, and diameter then photo-crosslinked. The number of scaffolds available for testing was limited by the amount of polymer that could be synthesized. A high-performance liquid chromatography method was developed specifically for this experiment and used to determine daily release of mafenide from the scaffold into a 2-mL phosphate buffer solution. During the first 24 hours a large …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

Optimization Of Gelatin-Based Cellular Coating Of Msc For Myocardial Infarction Therapy, Kara Amelle Davis

Theses and Dissertations--Chemical and Materials Engineering

Cardiovascular disease remains the number one threat to American lives. During an acute myocardial infarction (AMI), blood flow is blocked and results in the formation of scar tissue. As the body’s immune system responds, inflammatory signaling causes an increase in both scar tissue size and the patient’s risk for further chronic heart failure. In order to reduce the risk of continued heart disease inflammatory signaling must be reduced. Stem cell therapies have the ability to alter the immune system’s pro-inflammatory signal. However, stem cell retention is limited due to blood flow shear. Gelatin methacrylate (GelMA) based coatings have been shown …

Therapeutic Modalities For Preventing Osteoarthritis Following Trauma To The Knee, Kayla M. Scott

Theses and Dissertations

Over 32.5 million adults in the United States and 300 million worldwide have osteoarthritis (OA). To date, there are no disease-modifying therapeutics, only strategies to slow OA progression through pain management, regenerative medicine approaches, and ultimately joint replacement.

On a microscale, a phenotypic shift of the normally quiescent articular chondrocytes leads to aberrant expression of pro-inflammatory and catabolic pathways, which are hypothesized to contribute to OA progression. Of note, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling are key players disrupting cartilage homeostasis and driving inflammatory pathway activation. These pathways become dysregulated and form a positive feedback loop, increasing …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …