Defense Date


Graduation Date

Spring 5-13-2022


One-year Embargo

Submission Type


Degree Name



Chemistry and Biochemistry


Bayer School of Natural and Environmental Sciences

Committee Chair

Ellen S. Gawalt

Committee Member

Mihaela Rita Mihailescu

Committee Member

Stephanie J. Wetzel

Committee Member

Wilson S. Meng


biomaterials, scaffold, implant, EAK, clEAK, IOL, LVAD, thrombus, cell


This work encompasses three individual projects concerning biomaterials and their modifications. Chemically-Induced Cross-Linking of Peptidic Fibrils for Scaffolding Polymeric Particles and Macrophages EAK16-II (EAK) is a self-assembling peptide (SAP) that forms β-sheets and βfibrils through ionic-complementary interactions at physiological ionic strengths. The soft materials can be injected in vivo, creating depots of drugs and cells for rendering pharmacological and biological actions. The scope of the applications of EAK is sought to extend to tissues through which the flow of extracellular fluid tends to be limited. In such anatomical locales the rate and extent of the fibrilization are limited insofar as drug delivery and cellular scaffolding would be impeded. A method is generated utilizing a carbodiimide cross-linker by which EAK fibrils are pre-assembled yet remain injectable soft materials. It is hypothesized that the resulting de novo covalent linkages enhance the stacking of the β-sheet bilayers, thereby increasing the lengths of the fibrils and the extent of their crosslinking, as evidenced in Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy, scanning electron microscopy, and atomic force microscopy analyses. The cross-linked EAK (clEAK) retains polymeric microspheres with an average diameter of 1 μm. Macrophages admixed with clEAK remain viable and do not produce the inflammatory mediator interleukin-1β. These results indicate that clEAK should be investigated further as a platform for delivering particles and cells in vivo. Attachment of a Low Molecular Weight Heparin to Titanium Dioxide for the Prevention of Fibrin Clotting Heart failure is the primary cause of death for millions of Americans per year. Those in the end stages of heart failure require a heart transplant but donor hearts are scarce and patient needs are doubling. The Left Ventricular Assist Device (LVAD) serves as a bridge-to-transplant (BTT) method to hold the patient over until a donor heart becomes available or to provide comfort in the final stages of the disease as a destination therapy (DT). These devices constantly pump blood throughout the body and contain a large motor chamber that is in constant contact with the blood flow. Exposure to the blood leads to pump thrombosis which is the formation of clots on the pump motor’s surface. These clots could prevent the motor from turning over, which would stall the blood supply to the body, or the internal rotor could dislodge a clot which may cause an ischemic stroke. Typically, LVADs need replaced every 10 years to deal with the effects of pump thrombosis. To lessen the chances of clotting, patients are put on daily anticoagulant regiments that systemically prevent thrombin formations. This now causes the patient to be a bleed risk vi for any additional operations they may need. A coating comprised of a thiol-terminated self-assembled monolayer (SAM) and an immobilized low-molecular weight heparin (LMWH) has been described in order to locally prevent clots from forming on the titanium dioxide (TiO2) surface of the LVAD motor while allowing clotting to continue elsewhere in the body. After reacting the anti-thrombin drug enoxaparin sodium (ES) with the thiol SAM, the attachment was confirmed using DRIFT IR and Contact Angle. The effectiveness of the drug was observed in experiments which flowed calcium-spiked plasma over the surface before analysis with SEM. Micrographs showed that the bare metal and SAM-coated surfaces had widespread clot formations, but the ES immobilized surface had only inactive clots dusting the surface. Fibroblast studies exhibited that the modifications to the surface were not cytotoxic and that any potential toxic effects were not the cause of the anti-clotting activity observed in the plasma trials. The characterization and plasma trial results show that this SAM immobilized anticoagulant coating should be investigated further in vivo. Optimization of a High Refractive Index, Hydrophobic Intraocular Lens Material Cataracts are a common issue of the aging population. Approximately half of Americans will experience cataracts by 2050 according to the National Institute of Health. When cataracts become severe enough to warrant a lens replacement intraocular lenses (IOLs) are used in place of the clouded lens. Various types of lenses are available including monofocal, multifocal, and toric. Common materials for the lenses are hydrophobic or hydrophilic acrylic monomers. Certain benefits and hinderances are found with these lenses. Hydrophobic lenses tend to have great bioahdesiveness post-surgery and low risk of posterior capsule opacification (PCO). However, glistenings that can scatter light and vii obstruct vision are prevalent due to the nature of the polymers used. Hydrophilic materials experience the opposite occurrences with no glistenings but high risk of PCO. The monomers that comprise the lenses also play a role in physical properties such as glass transition temperature (Tg), water content, and the focus of this work, refractive index (RI). The RI determines how thick or thin an IOL can be based on the passage of light. Herein we describe two new formulations optimized from a high RI hydrophobic material. Sterically bulky monomers of the original material were removed in favor of butyl acrylate (BA) and 2-hydroxyethyl methacrylate (HEMA) to reduce the RI from 1.56 to 1.50 to ease manufacturing. HEMA was added in an attempt to include a small amount of hydrophilicity to the product. Additional analysis with ATR-IR showed that the functional groups present in the original formulation are retained in the formulations with monomer substitutions. Surface topography was observed using SEM and demonstrated that the surface became smoother after the addition of BA and had less surface texture after the introduction of HEMA. Water uptake, content, thermogravimetric analysis, and differential scanning calorimetry were also collected to fully characterize the materials. These optimized formulations are optically clear, flexible, have the desired RI for machining, a low Tg, and a high water content that may lead to a reduction in glistenings.



Additional Citations

Armen, J. M., Schueller, N. R., Velankar, K. Y., Abraham, N., Palchesko, R. N., Fan, Y., Meng, W. S., Gawalt, E. S., Chemically-Induced Cross-Linking of Peptidic Fibrils for Scaffolding Polymeric Particles and Macrophages. Macromol. Biosci. 2021, 21, 2000350.