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Theses and Dissertations

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Browsing Theses and Dissertations by Subject "biomaterials"

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    Failure analysis and durability enhancement of polymeric heart valve leaflets
    (Colorado State University. Libraries, 2024) Khair, Nipa, author; James, Susan P., advisor; Bailey, Travis S., advisor; Li, Vivian, committee member; McGilvray, Kirk, committee member
    Rheumatic and calcified aortic heart valve disease is prevalent globally among all aged people, and the number is rapidly increasing. Clinically accepted, minimally invasive xenograft-based transcatheter aortic heart valve replacement (TAVR) shows limited durability (<10 years). Hyaluronic acid (HA) enhanced polyethylene polymeric TAVR shows excellent in vitro and in vivo anti-calcific, anti-thrombotic, and hydrodynamic performance, making it a suitable candidate for heart valve leaflets. The main problem, however, is during durability testing, cyclic impact loading causes premature failure in a consistent fashion related to TAVR assembly. This dissertation investigates leaflet premature failure mechanisms and provides two plausible solutions to upgrade heart valve durability without sacrificing performance. With regard to the failure mechanism, representative areas of retrieved failed leaflets are examined under electron microscopy and small angle x-ray scattering. The investigation finds abrasive wear, wear polishing, fine scratching, and imprints of the metal stent of the leaflet surface, indicating surface wearing from soft plastic rubbing against hard metal. A strong permanganate oxidizer etches away low-energy amorphous domain to unveil stable spherulitic structures of approximately 3 µm, bridging and tie molecular domains of pristine LLDPE. The oxidizer partially etches away polymeric buildups of failed leaflets only to reveal thinned-out and fractured spherulites beneath them, identifying the buildups as stress precursors. SAXS study reports local lamellar disruption further confirming the SEM results. Most. Notably, this is the first study that, to our knowledge, to directly image stable craze cross-tie microstructure that formed due to chain disentanglement from high amplitude cyclic stress. The SEM images validate previous theoretical and computational molecular dynamics models of cross-tie structure architecture. Therefore, leaflet premature failures are the compound effect of cyclic fatigue-initiated crazing and surface wear. Heart valve leaflet durability can be upgraded by controlling crazing and surface wearing. Both the crazing and surface wearing can be controlled by crosslinking of randomly folded amorphous chains. Because they are direct impacts of chain disentanglement under high amplitude cyclic stress. Crosslinked covalent bonds of polymer limit chain movements. LLDPE thin sheets are crosslinked at 50, 70, 100, and 150 kGy doses using 200 KeV (low energy) and 4 MeV (low energy) electron beams at room temperature in the air. Their effects are characterized by measuring gel content percentage, tensile testing, Differential Scanning Calorimetry (DSC), nanoindentation, and nano scratch test. Crosslinked LLDPE heart valve leaflet tested in in vitro flow loop and wear tester to determine valve performance and durability, respectively. Low energy electron beam (LEEB) forms 28% xylene insoluble gel whereas high energy electron beam (HEEB) forms 58 % gel at 100 kGy doses. LEEB does not affect mechanical properties, but HEEB significantly increases stiffness and yield strength. A slight reduction of melting temperature is found for LLDPE crosslinked by both of the energy sources. Nanomechanical tests show crosslinking improves hardness and coefficient of friction, an indication of improving surface wear resistance, which can explain durability improvement. Heart valve durability can also be improved by strengthening the leaflet with fiber reinforcement. A thin plastic sheet is assembled into a cylindrical form by welding two ends, which never fails. The weld at the commissure post is found to be mechanically stronger than the rest of the leaflet, which protected this region. Braided fibers are embedded on the leaflet regions of the commissure post perpendicular to the valve circumference, mimicking the weld but at a much higher strength. Leaflet durability skyrockets from a few million ISO 5840-2005 cycles to 73 million. The entire cardiac cycle of the heart valve with embedded fibers of varying angles, lengths, and numbers is simulated in Finite Element Analysis (FEA) to study their effects on leaflet maximum principal stress and leaflet opening dynamics. Horizontal fibers wrap the leaflet 360° to relax the leaflet completely during peak diastolic. However, the leaflet has a higher coaptation gap and delayed opening. The heart valve with embedded horizontal fibers is physically manufactured and tested in an in vitro flow loop and wear tester, which showed improved durability, but compromised hemodynamics. Finally, strategically crosslinked leaflet was simulated in FEA where leaflet regions of the commissure post and stent line are assigned with stiff crosslinked LLDPE material property, but the rest of the cusps undergo maximum bending are assigned with uncrosslinked LLDPE material property. Results show that strategically crosslinked leaflets open more easily than fully crosslinked leaflets. The final chapter discusses 3D shaped LLDPE leaflet bio enhancement process. Leaflets are 3D shaped in a vacuum thermoformer followed by the HA enhancement. Whole blood clotting resistance, platelet adhesion, activation, and cytotoxicity studies are conducted to determine at 10-4 µmol/mm2 ranged HA population density is required to achieve the best biocompatibility. Generally, water contact angle, Toluidine Blue O (TBO) elution assays, ATR-FTIR are used to determine overall HA presence on the leaflet. This study reports TBO staining and elution is the most effective and accurate measurement tool for determining HA population density. Fiber-reinforced LLDPE, and crosslinked LLDPE are HA-treated, and TBO staining predicts heavily populated HA surface density.
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    Tuning interfacial biomolecule interactions with massively parallel nanopore arrays
    (Colorado State University. Libraries, 2021) Wang, Dafu, author; Kipper, Matt J., advisor; Snow, Chris D., advisor; Bailey, Travis S., committee member; Stasevich, Tim J., committee member
    This project studied interfacial interactions of macromolecules with nanoporous materials, with an ultimate goal of exploiting these interactions in functional biomaterials. We quantified interaction forces and energies for guest molecules threaded into the pores of protein crystals via nano-mechanical atomic force microscopy (AFM) pulling experiments. We demonstrated that both double-stranded DNA and poly(ethylene glycol) are rapidly absorbed within porous protein crystals, where they presumably bind to the inner "wall" surfaces of the protein crystal nanopores. These "guest" molecules can be retrieved from the "host" crystal by chemically modified AFM tips, enabling precise measurements of the adhesion forces and interaction energies. Based on these experiments, machine learning approaches were developed to classify hundreds of thousands of individual force-distance curves obtained in the AFM experiments. Furthermore, we showed that the interactions between protein crystal "hosts" and "guest" macromolecules can be used to modulate cell behavior, by presenting cell adhesion ligands tethered to different lengths of macromolecules that thereby modulate the maximum traction force cells can apply before rupturing bonds tethering the adhesion ligand to the porous protein crystal interior. This method affords the opportunity to create biomaterials that store an internal reservoir of cell-specific signals that can be presented to independently modulate the behavior of different cell populations in a single material. In the first chapter, some recent advancements, and methodologies of measuring interfacial biomolecule interactions are reviewed and compared. The reviewed technics include atomic force microscopy, fluorescence recovery after photobleaching, the total internal reflection fluorescence, confocal microscopy, and optical tweezers. Furthermore, this chapter interduces the application of machine learning to assist the interfacial biomolecule interaction studies, especially the AFM measurements. This chapter further prospects of the future of interfacial biomolecule interactions studies. In the second chapter, the methodologies of probing and observing the surface of highly porous Camphylobacter Jejuni formed protein crystals (CJ protein crystals) by high-resolution AFM are introduced. Throughout this chapter, the morphologies of CJ protein crystals are comprehensively investigated by AFM and have been discussed in this chapter. In the third chapter, for the first time, the interactions of DNA with porous protein crystals are quantitatively measured by high-resolution AFM and chemical force microscopy. The surface structure of protein crystals with unusually large pores was observed in liquid via high-resolution AFM. Force-distance (F-D) curves were also obtained using AFM tips modified to present or capture DNA. The interactions of DNA molecules with protein crystals to be quantitatively studied while revealing the morphology of the protein crystal surface in detail, in buffer, reveals how a new protein-based biomaterial can be used to bind DNA guest molecules. In the fourth chapter, strategies of machine learning are introduced which pioneered the use of machine learning to classify and cluster the interaction patterns between DNA and protein crystals, enabling us to process thousands of F-D curves collected by AFM. Finally, in the fifth chapter, we quantitatively measure and take advantage of the interaction between poly(ethylene glycol) (PEG)-arginine-glycine-aspartic acid (RGD) complex and nanoporous protein crystals to understand how non-covalent surface presentation of peptide adhesion ligands can influence cell behavior. Through AFM, F-D curves of interactions between PEG-RGD and host protein crystals were obtained for the first time. Furthermore, a strategy is developed that enables us to design surfaces that non-covalently present multiple different ligands to cells with tunable adhesive strength for each ligand, and with an internal reservoir to replenish the precisely defined crystalline surface.