Tissue engineering encompasses many important medical applications that pertain to the repair and regeneration of various tissues throughout the human body that have been adversely affected by disease or injury. Through combining the body’s cells with synthetic scaffolds, tissue engineering promotes proliferation of cells at damaged sites. Recent advances have demonstrated that using biocompatible materials such as alginate hydrogels—polymer networks derived from brown algae—are a cheap and environmentally-friendly approach to this. Alginate hydrogels are effective because they mimic the extracellular matrix of tissues, which provides structural support to cells that comprise human tissues.
One necessary modification to these scaffold materials is to load them with drugs that can facilitate healing. More complex designs can ideally deliver more than one therapeutic species simultaneously. In addition to hydrogels, drugs can also be loaded into a material known as porous silicon (pSi). pSi nanoparticles can be physically entrapped inside alginate hydrogels to create a two-system drug delivery mechanism with sustained release. This allows drugs such as growth factors, substances that stimulate cell growth, to be released at different times as the pSi and alginate hydrogel degrade.
This project entails the construction of alginate hydrogels that incorporate model dye-loaded pSi particles. The release of two dye molecules known as curcumin and rhodamine were monitored to assess the efficacy of the two-system drug delivery mechanism. It was first found that curcumin was too hydrophobic of a dye to achieve significant loading in the pSi. Rhodamine was found to be released from the pSi/alginate hydrogel system in a more incremental (sustained) manner over time compared to a relatively large initial ‘burst’ release observed for the release of rhodamine from pSi only. Sustained release in drug delivery is important to ideally reduce the amount of drug necessary and contrasts a burst release where large amounts of the loaded molecules are released prior to achieving a stable release profile. Furthermore, the localization of pSi in the alginate hydrogels was achieved by inserting loaded pSi membranes into pre-gelled alginate hydrogels, which is important to control the spatial delivery of the loaded molecule from pSi. Overall, it is believed that this pSi/alginate hydrogel material can greatly benefit the field of tissue engineering by creating dual delivery platforms with more diverse control over drug release.

It is estimated that 50 million individuals worldwide live with Alzheimer’s disease (AD), a neurodegenerative progressive disorder that, along with other chronic dementias, cost the United States $355 billion in 2021. Previous research links AD with amyloid beta (A𝛽) aggregation in the brain. Possible therapeutic drugs, including antioxidants and metal chelating agents, need efficient delivery systems that can cross the blood-brain barrier and release drugs appropriately. Recent discoveries in nanoscale materials as targeted drug delivery and controlled release agents have shown that such materials can release therapeutic drugs in a slow manner and increase efficacy. Chief among these carriers are porous materials with high surface areas because of their tunable pore structure, surface chemistry and drug loading capacity. This project focuses on using porous silicon derivatives as a carrier because, in addition to the above properties, it is a known biocompatible material.
This research deals with developing efficient protocols for loading mesoporous silica (pSiO2) with selected metal ion binding agents through systematic manipulation of external variables in order to achieve the highest percentage of loading. Once this has been determined, release and complexation studies are conducted. Known spectrophotometric methods are used to monitor diffusion over time and evaluate the profile of the sustained release. Different derivatives of chelating agents are tested and compared to determine the best suited candidates. The macrocyclic molecule Pyclen was the first tested candidate, followed by its dimer form, and finally a halogen substituted derivative. Stoichiometric complexation ratios with copper ions are measured followed by testing their success of inhibiting amyloid beta aggregation. Developing a slow and steady rate at which drugs capable of inhibiting neurotoxic A𝛽 aggregates in the brain can be released should be more effective and lead to more promising solutions for AD.

The misregulation of reactive oxygen species (ROS) and transition metal ions contributes to the onset of Alzheimer’s Disease (AD). A series of new pyridinophane ligands with indole (L2 and L3) and 4-methyl-8-hydroxyquinoline (L4) modifications were evaluated as a means of targeting the molecular features of AD. These studies contribute to the overall understanding of the therapeutic potential of the pyridinophane backbone as a means of treating AD. In comparison to the parent molecule L1, the order of radical scavenging activity was determined to be L4 > L1 ~ L3 > L2, which is likely related to the reactivity and position of the substitutions. These results demonstrate that the addition of (1) the indole moiety to the pyridine, and (2) the addition of the 4-methyl-8-hydroxyquinoline moiety to the secondary amine on the tetra-aza macrocyclic pyridinophane both disrupt radical scavenging ability, warranting future exploration of these modifications in therapeutic design for AD.

To accomplish many critical reactions and interactions mediated by metals like zinc and copper, Nature uses the amino acid cysteine—often in pairs—that are preorganized in space by a protein. Cysteine proteases are illustrative of the former; zinc finger transcription factors of the latter. Small molecule models of these proteins can serve many roles. They can shed light on the chemical process or ape them for therapeutic gain. Here, a macrocycle is used to preorganize two cysteine residues. These macrocycles are synthesized in three steps. The route begins with a stepwise substitution of a BOC-protected hydrazine group, a protected cysteine, and dimethylamine onto a triazine ring. Next, an acetal is appended onto the compound. Finally, a macrocycle is produced using an acid-promoted homodimerization. The macrocycle product has been characterized using 1H and 13C NMR in 1D and 2D experiments. Additionally, logP, variable temperature NMR, and H/D exchange experiments will be performed to understand the shape of the macrocycle in solution. These studies conclude with a study of how these cysteines bind metal ions. The results of this work will guide their development for biomedical applications including their use as drugs.

Various semiconductor metal oxides such as ZnO, TiO2, WO3, and BiVO4 have been utilized for photoelectrochemical (PEC) water-splitting as well as for value added alternative reactions. However, single-phase materials often face multiple challenges including poor charge separation efficiency and surface degradation especially in aqueous environment. BiVO4 is well known as a promising photoanode material, but the above-mentioned shortcomings are still present. Therefore, in order to enhance the PEC performance of BiVO4,our group has focused on doping techniques for BiVO4 with tungsten (W) to yield tungsten doped BiVO4 (W:BiVO4). In addition, polyethylene glycol (PEG) has also been introduced to the material as a morphological control agent. The addition of polymer to the precursor solution helps to control the porosity of the resulting surface film by promoting a less porous and more compact formation of BiVO4 on FTO. The mixture of PEG (1% MW 100,000 : 1% MW 20,000) has been tested. The photochemical oxidation of a solution containing (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) has been performed in acetonitrile with 0.1 M tetrabutylammonium hexafluorophosphate (TBAPF6) electrolyte. As a result, photocurrent density of PEG (1% MW 100,000 : 1% MW 20,000) - W:BiVO4 (0.58 mAcm-2 with an applied biased of 0.3 V vs. SCE) has outperformed that of W:BiVO4 without PEG (0.32 mAcm-2). Based on the data obtained, PEG(1% MW 100,000 : 1% MW 20,000) -W:BiVO4 outperformed W:BiVO4 by about 2 times. In the future, the best performing electrode samples will be studied for driving TEMPO-mediated benzyl alcohol oxidation.