Browsing by Author "Prawel, David, committee member"
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Item Embargo Development of an artificial temporomandibular joint disc replacement(Colorado State University. Libraries, 2023) Kuiper, Jason Paul, author; Puttlitz, Christian M., advisor; Prawel, David, committee member; McGilvray, Kirk, committee member; Henry, Charles, committee memberThe temporomandibular joint (TMJ) is a complex bilateral ginglymoarthroidal joint containing a fibrocartilaginous disc and is essential for chewing, speaking, and swallowing. Due to the high loading frequency, small imbalances in joint homeostasis can overcome the natural capacity for adaptation and lead to a cascade of degenerative changes. For progressive TMJ disorders, resection of the TMJ disc is the leading treatment, but disc resection inherently increases stress and friction on the articular cartilage surfaces, leading to a progression to total joint replacement in 11.7% of patients. The current methods of treatment for disorders of the TMJ musculoskeletal complex are predominantly palliative and do not reliably address disorders of arthrogenous origin. Unfortunately, no synthetic TMJ disc replacements currently exist due to profound implant failures in earlier attempts. Introduction of a robust artificial TMJ disc replacement after resection will prevent further joint degradation and improve patient outcomes. Rigorous preclinical evaluation of artificial TMJ disc replacement strategies must be conducted to support future translation to humans. Therefore, the following aims are proposed: (1) Characterize the biomechanical behavior of the ovine temporomandibular joint soft tissues, (2) identify and evaluate a material candidate for a temporomandibular joint disc replacement, (3) develop in silico and in vitro methods for evaluating design candidates for artificial TMJ disc replacement, and (4) implement a temporomandibular joint disc replacement strategy in an ovine model.Item Embargo Engineered mRNA therapeutic encoding beta-catenin increased bone formation in a murine tibial fracture model(Colorado State University. Libraries, 2023) Nelson, Anna Laura, author; Ehrhart, Nicole, advisor; Bahney, Chelsea, advisor; Huard, Johnny, committee member; Popat, Ketul, committee member; Prawel, David, committee memberFractures continue to be a global economic burden and impaired fracture healing cases, like delayed and non-union, occurring in about 14% of all tibial shaft fractures. Current treatments to aid in fracture healing involve surgical interventions and osteoanabolic, bone-morphogenetic protein-2 (BMP-2), yet is challenged supraphysiological doses and adverse side effects. Given the limited treatment options available, there remains a clinical need to develop injectable therapeutics to accelerate fracture healing in impaired fracture healing cases. Mechanistic data reveals β-catenin as a molecular driver in endochondral ossification. The central hypothesis for this dissertation is a stabilized, non-destructive β-catenin mRNA delivered locally in the fracture callus can accelerate fracture healing in a murine tibia fracture healing model. Using mRNA therapeutically continues to be challenged with stability and immunogenicity of the mRNA. To circumvent these limitations, delivery carriers have been employed to maximize gene stability, minimize off-target effects, and reduce immunogenicity. Recent advancements in liposomal technologies have led to the development of lipid nanoparticles (LNPs), leading to successful clinical translation of several novel and highly effective therapies, like SARS-CoV-2 vaccine. Alternative delivery carriers have emerged involving use of mineral coated microparticles (MCMs) as a biomimetic and biocompatible system to deliver liposomes at the site of a fracture in a controlled manner. Here, we explore mRNA delivery carriers for fracture healing applications, including manufactured cationic liposomes, MCMs, LNPs and a combination of these carriers. Manufactured liposome, Lipofectamine™, was found to be prolong transfection when tested in a murine fracture model in vivo as compared to TransIT Transfection Reagent. Using Lipofectamine™ to deliver mRNA, chemically-doped MCMs enhanced transfection and stimulated bone in vitro when delivered in chondrocytes. When testing these platforms in a murine tibia fracture model, chemically-doped MCM did not promote bone expression through testing RNA in the fracture callus for bone-related genes and through histomorphometry of the fracture callus 2 weeks post-fracture. The chemically doped MCM was found to prolong transfection of reporter gene, firefly luciferase mRNA, in vivo when compared to other treatment groups including the liposome and mRNA complex (lipoplex) alone. Ionizable-based LNPs are positively charged at a low pH and net neutral at physiological pH. Two FDA-approved ionizable phospholipids, MC3 and SM-102, were used to generate ionizable LNPs. First, MC3 LNP was tested for transfection capacity when combined with MCMs. While chemically-doped MCMs when combined with firefly luciferase mRNA encapsulated MC3 LNPs showed improved transfection in vitro, no improvements in transfection efficacy were found in vivo. Next, MC3 and SM-102 LNPs were then complexed with reporter gene, firefly luciferase mRNA to test transfection potential, immunogenicity, fracture interference and biodistribution in vitro and in a murine fracture healing model. SM-102 LNPs showed enhanced transfection efficacy in vitro, prolonged transfection in vivo, minimal fracture interference in vivo and showed no localized inflammatory response in the murine fracture callus. Ex-vivo IVIS images of main organs revealed no biodistributive effects when delivering SM-102 complexed with mRNA locally to the site of the fracture callus. Capitalizing on prior mechanistic data showing β-catenin's critical role in chondrocyte to osteoblast transdifferentiation, a non-destructive β-catenin, β-cateninGOF, mRNA transcript was generated using nucleoside modification, N1-methyl-pseudouridine, and cap analog, CleanCap. When testing the generated β-cateninGOF mRNA encapsulated in SM-102 LNPs in vitro for bioactivity, downstream canonical Wnt genes were significantly upregulated. When testing SM-102-β-cateninGOF mRNA therapeutic in murine tibia fracture model, more bone and less cartilage composition compared to PBS control was determined when analyzing histomorphometry at 25 and 45 μg concentrations at 2 weeks post-fracture. To further confirm SM-102-β-cateninGOF mRNA therapy's capabilities to promote bone in vivo, μCT was performed revealing significantly more bone volume over total volume with 45 μg dose as compared to PBS control. Taken together, we generated a novel mRNA based therapeutic encoding a non-destructive β-catenin mRNA and optimized ionizable LNP, SM-102, to maximize transfection efficacy with a localized delivery. This SM-102-β-cateninGOF mRNA therapeutic may accelerate fracture healing in a murine tibia fracture healing model.Item Open Access Fundamental and applied studies of polymeric photonic crystals: the role of polymer architecture and 3D printing(Colorado State University. Libraries, 2020) Boyle, Bret Michael, author; Miyake, Garret, advisor; McNally, Andrew, committee member; Menoni, Carmen, committee member; Prawel, David, committee memberBlock copolymers (BCP) provide a bottom-up, economical approach to synthesizing polymeric photonic crystals (PC) through the process of self-assembly. Photonic crystals (PC) are defined as periodic, dielectric nanostructures able to reflect certain wavelengths of light within a photonic band gap. The ability to directly tailor the synthesis, conformation, and self- assembly of a BCP to affect the properties of the resulting PC material creates a modular platform for PC materials design. Even though this platform exists for polymeric PC materials, the direct result of modulating the polymer architecture on the dynamics, self-assembly, and application of PC materials remains relatively unexplored. To help close this gap, this dissertation presents the polymer synthesis, characterization, and self-assembly of macromolecules within two unique classes of polymer architecture, dendritic block copolymers (DBCP) and bottlebrush block copolymers (BBCP). DBCPs were shown to possess many characteristics similar to those of bottlebrush polymers such as a rod-like conformation, a reduced capability for chain entanglement, and lower glassy moduli compared to non-rigid, linear polymers. Further, DBCPs possess high free energy parameters, as well as glass transition temperatures below melt extrusion 3D printing operating conditions, and were shown to self- assemble into PCs during the process of 3D printing. DBCP PCs represented the first example of 3D printing structural color. For BBCPs, the backbone composition's effect on the global BBCP conformation and in modulating self-assembly processes was examined. The backbone composition was shown to dramatically shift the wavelength of reflection of the PC material at similar molecular weights as well as improve the fidelity of the nanostructure morphology as the molecular weight increases from 50,000 g/mol to 2 million g/mol. The structure-property relationships illuminated herein have laid the groundwork for new research efforts into engineering BCPs for novel PC applications.Item Open Access Generalized pressure drop and heat transfer correlations for jet impingement cooling with jet adjacent fluid extraction(Colorado State University. Libraries, 2022) Hobby, David Ryan, author; Bandhauer, Todd M., advisor; Olsen, Daniel B., committee member; Prawel, David, committee member; Venayagamoorthy, Karan, committee memberJet impingement technologies offer a promising solution to thermal management challenges across multiple fields and applications. Single jets and conventional impinging arrays have been studied extensively and are broadly recognized for achieving extraordinary local heat transfer coefficients. This, in combination with the versatility of impinging arrays, has facilitated a steady incline in the popularity of jet impingement investigations. However, it is well documented that interactions between adjacent jets in an impinging array have a debilitating effect on thermal performance. Recently, in an attempt to mitigate the jet interference problem, a number of researchers have created innovative jet impingement solutions which eliminate crossflow effects by introducing fluid extraction ports interspersed throughout the impinging array. This novel adaptation on classical impinging arrays has been shown to produce dramatically improved thermal performance and offers an excellent opportunity for future high-performing thermal management devices. The advent of jet-adjacent fluid extraction in impinging arrays presents a promising improvement to impingement cooling technologies. However, there have been very few investigations to quantify these effects. Notably, the current archive of literature is severely lacking in useful, predictive correlations for heat transfer and pressure drop which can reliably describe the performance of such impinging arrays. Steady-state heat transfer and adiabatic pressure drop experiments were conducted using nine unique geometric configurations of a novel jet impingement device developed in this work. This investigation proposes novel empirical correlations for Darcy friction factor and Nusselt number in an impingement array with interspersed fluid extraction ports. The correlations cover a broad range of geometric parameters, including non-dimensional jet array spacing (S/Dj) ranging from 2.7 to 9.1, and non-dimensional jet heights (H/Dj) ranging from 0.31 to 4.4. Experiments included jet Reynolds numbers ranging from 70 to 24,000, incorporating laminar and turbulent flow regimes. Multiple fluids were tested with Prandtl numbers ranging from 0.7 to 21. The correlations presented in this work are the most comprehensive to date for impinging jet arrays with interspersed fluid extraction. Nusselt number was found to be correlated to impinging jet Reynolds number to the power of 0.57. The resulting correlation was able to predict 93% of experimental data within ±25%. During adiabatic pressure drop experiments, multiple laminar-turbulent flow transition regions were identified at various stages in the complex jet impingement flow path. The proposed Darcy friction factor correlation was separated into laminar, turbulent, and transition regions and predicted experimental data with a mean absolute deviation of 20%. The heat transfer and pressure drop correlations proposed in this investigation were used in a follow-on optimization study which targeted an exemplary impingement cooling application. The optimization study applied core experimental findings to a microchip cooling case study and evaluated the effects of geometry, flow, and heat load parameters on cooling efficiency and effectiveness. It was discovered that reducing non-dimensional jet height results in all-around improved cooling performance. Conversely, low non-dimensional jet spacing results in highly efficient but less effective solutions while high non-dimensional jet spacing results in effective but less efficient cooling.Item Open Access Mechanical and antimicrobial performance analysis of a shark skin bio-mimicked fabric swatch via 3D printing(Colorado State University. Libraries, 2020) Purandare, Saloni Prasanna, author; Li, Yan Vivian, advisor; Yan, Ruoh-Nan, committee member; Prawel, David, committee memberBiomimicry is a long-practiced concept concerned with development of products with nature as the source of inspiration. Bio mimicked textiles is a branch of textiles wherein textile products are developed to replicate desirable elements of nature such as lotus-leaf inspired water repellent fabric, high-strength spider silk inspired by the spider web and shark skin biomimicry. The scaled texture on shark skin, known as riblet effect, exhibits drag reduction and antimicrobial properties. Accurate biomimicry of shark skin is an on-going continual process This study is concerned with 3D printing bio mimicked fabric swatches by replication of riblet effect followed by characterization of the developed fabric swatches. The swatches were printed using Autodesk Ember photopolymer 3D printer, allowing printing of minutely detailed denticles in the base. The materials used were polycarbonate/acrylonitrile butadiene styrene (PC/ABS) and polyurethane (PU) material. PU allowed creation of rigid tough denticles embedded in flexible and soft base, indicating as a better raw material to 3D print bio-mimicked swatches for functional clothing. The PU swatches were studied further in morphological, mechanical, and antimicrobial analysis. The morphological analysis resulted into optical images exhibiting the developed texture resembling characteristic riblet effect of shark skin. Mechanical analysis in terms of tensile stress testing exhibited stronger and tougher fabric samples with thick (1.05mm) base in comparison with those having thin (0.75mm) base. Also, the mechanical analysis indicated good elastomeric properties for the fabric swatches suggesting potential in functional clothing. Lastly, the antimicrobial test conducted exhibited reduced antimicrobial growth for samples with riblet texture against untextured samples, copper foil as well as aluminum foil thus exhibiting potential use of the textured fabric swatches as non-toxic antimicrobial material. Shark skin biomimicry through riblet effect replication has been studied majorly for hydrodynamic properties while shark skin inspired material intended for antimicrobial properties such as by Sharklet® technology is not concerned with riblet effect replication. Thus, to our best knowledge study focusing on mechanical and antimicrobial analysis of shark skin biomimicry through replication of riblet effect is missing. This study will help determine potential of shark skin biomimicry by replication of riblet effect in functional clothing, through mechanical and antimicrobial analysis.Item Open Access Penetrative osseointegrative phospholipid coatings on 3D titanium lattice structures(Colorado State University. Libraries, 2012) Hudson, Hannah Katherine, author; James, Susan, advisor; Prawel, David, committee member; Ehrhart, Nicole, committee memberTitanium is a commonly used material for implantable metallic devices though these devices still have many issues. The cost of implant surgery and the likely revision surgery that will follow is high. Cementless implants frequently fail due to aseptic loosening of the device, typically as a result of poor osseointegration. Phospholipids are naturally occurring substances that have been used to enhance new bone growth and integration of this bone with the implants. Electrospraying (e-spraying) is a method that uses electrical forces to drive source material to a target conductor. It typically has very high efficiency because it uses electrical charge to carry the material. This process also provides good control of coating morphology as this can be effected by the parameters used to e-spray. In our work the E-spraying technique was used to apply coatings of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) to Ti-6V-4Al porous lattice structures. These lattice structures are created using Electron Beam Melting (EBM). This manufacturing process is an additive process, part of the solid free form fabrication group, a subset of rapid prototyping. EBM enables precise control of complex geometries. When e-spraying these lattice structures can become Faraday cages when an electric field is applied to them. A Faraday cage is a conductor that becomes an equipotential surface when an electric field is applied and thus in its interior lacks an electric field. The exclusion of an internal electric field can inhibit to the e-spray process which relies on field lines to carry material to the target. In our work the Faraday cage effect was observed in two conditions, one in which the lattice structures were externally, circumferentially insulated and one in which the lattices were not insulated. Three different porosity lattices, with different pore sizes, were tested and all became Faraday cages when insulated and only the lowest porosity lattice became a strong Faraday cage when not insulated. The lattices that did coat did not exhibit conformal and uniform coatings when the Faraday cage effect was present. E-spray parameter variation was not able to mitigate the Faraday cage effect nor was it able to affect the morphology of the coatings. The surface topography of the structures is important for preferential cell adhesion and can be controlled using acid etching to modify the surface. In attempt to coat titanium lattice structures with a phospholipid coating this work discovered the Faraday cage effect as it relates to the electrospraying of phospholipids. It currently defines the limitations of the e-spray process as well as outlines what has been tried to mitigate the Faraday cage effect and discover how the Faraday cage effect changes coating morphology. In the future continuing work on mitigating the Faraday cage effect will be done as well as combining the e-spray process with one that uses a mechanical force to accelerate particles.Item Open Access Study of mechanical and antimicrobial properties of biomimetic shark skin fabrics with different denticle size via 3D printing technology(Colorado State University. Libraries, 2022) Wen, Jiayi, author; Li, Yan Vivian, advisor; Chisholm, Sandra, committee member; Prawel, David, committee memberPrevious studies have shown that biomimetic shark skin fabrics can reduce water drag and increase swimming speed. It was also known that the smaller the denticle was, the higher water drag reduction was. In nature, the size of the denticles on shark skin is between 100 μm and 500 μm. However, the minimum size of the 3D printed denticles on a biomimetic shark skin fabric previously reported was about 2mm, which was still much larger than the natural size. In this study, different sizes of denticles ranging from 0.65mm to 1.30mm were fabricated using a Form3 3D printer and Flexible80A resin, and the effect of denticle size on mechanical properties and antimicrobial properties of biomimetic shark skin fabric were evaluated for the applications in functional clothing. The results suggested that when the size of the denticle was decreased, the stiffness of the fabrics was increased. In the tensile testing, the tensile strength and the breaking elongation of the 3D printed fabric with 1.04mm denticles were largest in the tested fabrics, which was larger than those of some common fabric materials used in commercial swimwear, suggesting great potential of functional clothing applications. In addition, mechanical anisotropy was observed in the 3D printed fabrics, which is commonly seen in textile fabrics. In antimicrobial testing, the shark skin fabrics with 0.65mm and 1.04mm denticles were found to be less susceptible to bacterial attachment, suggesting good potential for functional clothing applications.Item Open Access Techniques in reactive to proactive obsolescence management for C5ISR systems(Colorado State University. Libraries, 2023) Chellin, Matthew D., author; Miller, Erika, advisor; Daily, Jeremy, committee member; Herber, Daniel, committee member; Simske, Steven, committee member; Prawel, David, committee memberObsolescence is a significant challenge for the Command, Control, Communications, Computers, Cyber, Intelligence, Surveillance and Reconnaissance (C5ISR) community. Obsolescence can negatively affect a C5ISR system's cost, schedule, performance, and readiness. This research examines the challenge of obsolescence for C5ISR systems by focusing on the U.S. Army at Aberdeen Proving Ground, Maryland and their industry partners. The objective of this research is to synthesize insights from the experiences of government and industry practitioners that mitigate diminishing manufacturing sources and material shortages (DMSMS) challenges into mitigation techniques. The obsolescence mitigation areas described in this research include proactive and reactive obsolescence mitigation, obsolescence mitigation methods, and the importance of DMSMS contracting language. This research also offers approaches grounded in practitioner experiences to mitigate obsolescence through a proactive obsolescence management model, risk mitigation framework, metrics, modeling & simulation, and systems thinking methods. The combination of the models, methods, and approaches discussed from this research have the potential to achieve greater system readiness, more availability, better maintainability, and lower costs for C5ISR systems.