Browsing by Subject "Biomaterials"
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Item Bioengineered tissue mechanics: experimental characterization and a multi-component model(2013-08) Lai, VictorIn the last few decades, tissue engineering has emerged as an interdisciplinary field of research which holds much promise as a complement to clinical medicine towards the overall improvement of personal health. Despite significant advances in this field, much work in TE continues to rely on an Edisonian approach of employing ad hoc methods to engineer tissues with desired properties without fundamental knowledge of the problem at hand. This thesis presents the development of a comprehensive model that predicts the mechanical properties of bioengineered tissue equivalents (TEs) based on its structure and composition, to enhance the understanding of the contribution of various biological components (e.g. biopolymeric fibers, cells, etc) to macroscopic mechanical properties of a tissue at different stages of tissue growth. The project framework considered bioengineered tissues as being composed of three components: fibrous networks, an interstitial matrix, and cells. The following interactions between different components were investigated: (a) multiple fiber networks, (b), fiber network + interstitial matrix, and (c) fiber network + cells. Experimentally, mechanical tests such as stress relaxation and tensile stretch to failure were coupled with electron microscopy, confocal microscopy, and biochemical analyses to probe tissue microstructure and composition. Constructs were formulated with varying compositions of the different components in a TE. These experimental results guided the development of the theoretical model. Modeling work built upon an existing single-component microstructural model by incorporating other components and morphological features as observed from experiment. Improvements to the model combined two approaches: (1) a microstructural approach via incorporation of morphological features observed from micrographs, and (2) a phenomenological approach using constitutive relations commonly employed for various biological structures. Model validation was done by comparing model predictions of mechanical behavior with experimental results; agreements and discrepancies alike shed insight into the complex interactions between different components the comprise a TE. Overall, the work presented in this thesis represented significant improvements to the predictive capabilities of our computational model, and established the foundation for further modifications to capture better the microstructure and mechanics of different components within a TE.Item Design of Silica-Collagen Nanocomposite for Corneal Replacement(2015-09) DiVito, MichaelThe cornea is the most commonly transplanted tissue in the United States. Globally, corneal diseases are the second leading cause of blindness. Due to strict FDA regulations, lack of eye banking facilities, and other factors which limit the supply of donor tissue, designing an artificial cornea made of readily available materials is of great interest. The synthetic constructs that are currently clinically available in the United States have had moderate success, but biocompatibility issues such as stromal melting and epithelial defects are still common. When considering a potential material for corneal replacement, it must meet the design criteria of the normal functioning cornea. The relevant design criteria can be broken down into three main groups: optical behavior, biomechanical properties, and biocompatibility. The presented work proposes silica-collagen nanocomposites as a viable candidate material to meet these design criteria. A bottom-up approach starting from the molecular level is utilized to modify the surface chemistry and physical properties of collagen fibrils. In doing so, methodologies are presented which allow for fine-tuning of optical, biomechanical, and biodegradation behavior. The first part of this work validates the theory that light scattering of collagen hydrogels is heavily dependent on the change in the material’s index of refraction over length scales comparable to the wavelength of incident light. This work shows that light scattering of collagen hydrogels can be minimized by a rapid neutralization technique, and by the addition of nanocrystalline cellulose. Additionally, collagen hydrogels with embedded magnetic nanowires can be polarized to form an aligned fibril microstructure and show an increase in light transmission. The second part of this thesis characterizes the mechanical and optical behavior, as well as the biocompatibility of silica-collagen nanocomposites. This work shows that a copolymerization method can be used to make implants which have improved biomechanical properties (when compared to pure collagen hydrogels) and can be re-epithelialized in an ex vivo rabbit model. Additionally, an improved two-step process for silica deposition onto collagen fibrils is presented. This new method shows that poly-L-lysine can be used to induce a uniform silica shell around collagen fibrils in the absence of large silica aggregates. This new method increases mechanical stiffness and enzymatic degradation resistance without producing any additional light scattering in the material. Silica-collagen nanocomposites show great potential in the context of corneal replacement. The methods developed and results presented here can be useful for improving any collagen-based corneal replacement, as well as in other applications such as drug delivery and silica nanoparticle templating.Item The Feasibility and Sustainability of Architectural Biomaterials(2016-04) Becker, Patrick J; Brownell, Blaine EThis research was centered on the development of a materials database as a resource for architects, designers,contractors,scientists, and consumers. A primary focus of the research is the feasibility and sustainability of materials with a metabolic or distinctly biological. Application of biomaterials and recycled materials can significantly reduce the impact of construction and the waste it generates. However,this application depends directly on the influence of architects in the design process, specifically material selection. The usage of the Transmaterial series, as a resource, can provide designers, architects, contractors, and end-users with access to cutting-edge materials that are changing the built environment.Item Investigating the Cytocompatibility of a Novel Flipped Ester Group Design Polymer Composites against Oral Keratinocytes(2022-05-09) Kumar, Dhiraj; Bolskar, Robert D.; Mutreja, Isha; Jones, Robert S.; rsjones@umn.edu; Jones, Robert S; Minnesota Dental Research Center for Biomaterials and Biomechanics; B-A-M (Biofilm-Apatite-Microbiome) Lab; TDA Research, Inc.The methacrylate based polymeric materials have been widely used in dentistry because of the ease in tuning the physico-mechanical properties along with their ability to polymerize at room temperature in a period of seconds without causing deleterious exothermal effects. However, these materials are susceptible to hydrolysis of functional ester groups in the polymer backbone which prompted the development of a novel designer polymer with ester groups present in the side chain instead of the polymer backbone. Previously we have compared the physico-mechanical and stability profile of the new polymer with traditional EGDMA using accelerated aging, esterase, and bacterial incubation models. Another important parameter for polymer design in biological systems, such as use in dentistry, is polymer biocompatibility. The goal of this pilot investigation was to assess the cytocompatibility of novel design polymer EGEMA compared to EGDMA, a diluting agent in dental formulations, and a commercially available formulation Helioseal® (Ivoclar Vivodent). Material discs of the EGEMA, EGDMA, and Helioseal® were test in the presence of oral keratinocytes (TERT-2/OKF-6). After assessing oral keratinocytes cellular metabolic activity and cell morphology, the investigation suggested EGEMA and EGDMA showed comparable cytocompatibility that was statistical more favorable than Helioseal®.Item Investigations of Self-Assembling Guanosine Phosphoramidate Based Hydrogels(2023-07) Bentz, NicolePeptides and nucleobases are supramolecular building blocks that have been widely investigated for their self-assembling properties and ability to form supramolecular structures. These high-aspect ratio structures eventually form entangled matrices that result in supramolecular hydrogels. Previous work in our lab incorporated enzymatic activity in the regulation of peptide self-assembly, where we investigated Histidine Triad Nucleotide Binding Protein 1 (Hint1) as a modulator of supramolecular self-assembly.1 In this work, we developed a panel of self-assembling nucleoside phosphoramidates (SANPs) capable of Hint1 triggered hydrogelation. SANPs are low molecular weight molecules that incorporate a self-assembling peptide conjugated to a nucleoside phosphoramidate group through a short PEG linker. A surprising observation in the development of these Hint1 responsive molecules was the spontaneous assembly of the SANPs into highly ordered nanofibers without enzymatic activity, and the unique ability of the guanosine SANPs to form supramolecular hydrogels.Guanosine and its derivatives have been of particular interest for researchers due to its unique ability to form G-quadruplexes that drive self-assembly, but their instability and tendency to precipitate from solution have limited the applications of these biomaterials. Herein, we report the unique interplay of two self-assembling moieties to drive supramolecular hydrogelation: an ultrashort self-assembling peptide and a guanosine nucleobase. This body of work details the fundamental investigation of our panel of SANPs and the influence of nucleobase identity on the critical aggregation concentration, stability, and hydrogelation ability of these molecules. Specifically, we examine the synergistic self-assembly of the guanosine SANPs and tease out the interactions that ultimately result in supramolecular hydrogelation. Characterization of these dual moiety guanosine SANPs reveal that the resulting hydrogels integrate principal properties of both supramolecular building blocks, resulting in a novel biomaterial that addresses the caveats of the traditional guanosine-based hydrogels. We further examined their innate biological activity and demonstrate the promising application of these novel biomaterials for controlled drug release with the potent chemotherapeutic Doxorubicin and assess the activity of our drug depot in vitro.Item A Novel Methacrylate Derivative Polymer That Resists Bacterial Cell-Mediated Biodegradation Data Sharing Archive(2021-11-22) Kumar, Dhiraj; Ghose, Debarati; Mutreja, Isha; Bolskar, Robert D.; Jones, Robert S.; rsjones@umn.edu; Jones, Robert S; B-A-M (Biofilm-Apatite-Microbiome) Lab; TDA Research, Inc.; School of DentistryWe studied biodegradation resistance of a custom synthesized (by TDA Research Inc) novel ethylene glycol ethyl methacrylate (EGEMA) with ester bond linkages that are external to the central polymer backbone when polymerized. Experiments were designed to compare degradation resistance with Ethylene glycol dimethacrylate (EGDMA) with internal ester bond linkages. The data has been published in an article titled "A Novel Methacrylate Derivative Polymer That Resists Bacterial Cell-Mediated Biodegradation" in the Journal of Biomedical Materials Research: Part B - Applied Biomaterials. The data in this record supports the figures in the published manuscript.