Chemical and Biomolecular Engineering - Theses
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ItemNo Preview AvailableMolecular Insights into Nanoengineered Metal–Phenolic Networks( 2023-06)Coordination assembly has garnered significant attention in designing advanced materials with well-defined geometry and functions for diverse applications across various fields. Metal–phenolic networks (MPNs) are supramolecular coordination network materials composed of metal ions and natural phenolic ligands. The distinctive combination of hybrid physicochemical properties and versatile coating ability have endowed MPNs with widespread potential in biomedical, environmental, and agricultural applications. However, despite recent advancements, regulating coordination chemistry in MPNs through different coordination modes remains largely unexplored and a challenge. A comprehensive understanding of this aspect and the associated knowledge is expected to significantly boost the development of MPNs with unique morphologies and properties for a wide range of fields. This thesis aims to expand the realm of MPNs by engineering their coordination modes and kinetic at the nanoscale, thereby imparting materials with controllable properties or emerging functions for various targeting applications. Firstly, the dynamic and selective coordination modes of MPNs were experimentally and computationally investigated using flavonoids with monotopic, ditopic, and multitopic chelating sites. The dominating coordination modes in MPNs could be adjusted from metal–catechol to metal–maltol by simply changing the assembly pH, leading to distinct crosslinked coordination networks and tunable physiochemical properties (e.g., selective permeability and pH-dependent degradability) for desired applications. Secondly, flexible MPNs featuring guest-responsive behavior were achieved by introducing intermolecular competitive coordination between MPNs and external guest molecules (e.g., glucose). Upon exposure to glucose molecules, glucose partially replaced flavonoids in MPNs due to the comparable intermolecular coordination of metal ions to flavonoid ligands and glucose. This led to the re-conformation of metal-organic networks and changes in their physiochemical properties, as demonstrated experimentally and computationally. The resulting cargo-loaded MPNs could be responsive to external guest stimuli, showcasing promising potential in smart drug delivery. Thirdly, a library of MPN nanoparticles with different compositions was fabricated by controlling the coordination kinetics of metal-phenolic complexes. The formation kinetics and physiochemical properties of MPN nanoparticles were systematically controlled by employing various strategies, including adjusting the incubation time, precursor types and concentrations, and the assembly pH. Moreover, various functional components (e.g., enzyme and drug) were incorporated with MPN to fabricate functional nanoparticles for desired biomedical applications, including cell targeting and drug delivery. These studies expand the understanding of the coordination chemistry of MPNs and provide a guideline for the rational design of metal-organic materials for broader applications.
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ItemSpider silk-inspired functional materials with tailored surface properties for biomedical applications( 2022)Biomaterials science is an increasingly important and constantly evolving field of science. Only intensive cooperation between different disciplines and a deep understanding of the physical and chemical interactions within developed materials and the biological system as a whole lead to the successful development of new biomaterials. Biocompatibility plays a central role here. It must be possible to assess whether the material is compatible with the respective application, e.g., implantation in hard or soft tissue. Here, a further distinction can be made between structural and surface compatibility. Structural compatibility covers the structure, shape, and mechanical property interactions in a biological environment. Surface compatibility summarizes the adaptation of chemical, physical, biological, and morphological surface properties to the biological environment. Consequently, the surface properties of a biomaterial are crucial for its biocompatibility and interactions with the host system. Materials used as biomaterials must fulfill a wide range of requirements. They should have excellent mechanical stability, be biocompatible and, depending on the requirements, bioinert or bioactive. For example, bioactive biomaterials are used to increase or control interaction with cells. Synthetic polymers usually have excellent mechanical properties but then lack biocompatibility, whereas natural polymers often have excellent biocompatibility but then are mechanically very weak and therefore not suitable for applications with high mechanical stress. A promising material that exhibits the advantages of both classes of polymers is spider silk. Spider silk has been used since ancient times as wound dressings and suture material as it is mechanically resilient and elastic and elicits little to no immune response. Natural spider silk cannot be used as a biomaterial on a large scale due to the cannibalistic behavior of most spider species and changing quality of silk. Therefore, this work presents two approaches utilizing materials inspired from natural spider silk to create functional, modifiable, mechanically resilient, and biocompatible coatings. The first approach is bioengineered recombinant spider silk proteins. Before biotechnological production, these proteins produced can be genetically modified in E.Coli bacteria. In this work, twelve different spider silk protein variants are used and investigated concerning their biocompatibility, biodegradability, and interaction with proteins, cells, and human blood. These spider silk protein variants are non-toxic and can be resorbed by the body as they consist solely of amino acids. The second approach is based on synthetic polypeptides prepared by the continuous assembly polymerization (CAP) method, published for the first time, using reversible-addition-fragmentation chain-transfer (RAFT) polymerization, or CAP-RAFT. Polypeptides were selected based on amino acids found in natural spider silk (L-lysine and L-glutamic acid). These coatings based on synthetic polypeptides were investigated concerning secondary structure and biodegradability. CAP-RAFT was established as a viable strategy to prepare surface-limited cross-linked polypeptide films with precise film thickness control and novel properties such as specific secondary structure formation and biodegradation. This variability of secondary structure combined with enzymatic degradation shows high potential for numerous biological applications. In the present work, secondary structure formation and assembly of the spider silk-inspired materials on coatings were investigated in detail. Firstly, the effect of coating thickness on the structural properties (beta-sheet fraction) was investigated from the nanoscale to the microscale. A coating thickness-dependent assembly and phase separation model is presented. In addition, the orientation of beta-sheets in recombinant spider silk coatings was investigated. Another important aspect of surface biocompatibility is the structure-property relationship of these spider silk-based materials. Concerning applications in the biomedical field, the interaction between material and biological environment is essential. Several aspects are studied in detail: specifically surface charge, surface chemistry, surface topography, and surface hydrophilicity. These aspects were analyzed to understand the interaction with proteins, cells, and blood as well as their biodegradability. Based on the results of the respective studies, it was possible to categorize the different spider silk variants into bioinert and bioactive variants and assign their subsequent potential biomedical applications. Positively charged spider silk protein variants are bioactive and have the most significant interaction with cells and blood. Modification with the cell-binding peptide improved cell adhesion of all variants used. Amino acid sequences based on the natural Araneus diadematus fibroin (ADF) 3 protein showed significantly faster enzymatic degradation than the protein variants based on the amino acid sequence of ADF4. The introduction of three-dimensional patterns on the coating surface can significantly increase the adhesion of cells to material (negatively charged variant), which shows little adhesion of cells as a smooth coating. In this dissertation, the structure formation, assembly, and structure-property relationships of spider silk-inspired materials were systematically investigated. These spider silk-inspired materials possessed a high potential for application in various biomedicine fields due to the diverse modification possibilities in terms of morphology, amino acid sequence, and charge.
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ItemProtein–Polyphenol Networks: From Fundamentals to Biomedical Applications( 2020)Naturally occurring building blocks have attracted scientific interest for the assembly of functional materials due to their intrinsic biocompatibility and biodegradability. Proteins are a particularly crucial class of functional biomacromolecules involved in most fundamental processes of living organisms that can be assembled into nanomaterials for various biomedical applications. Another ubiquitous class of biomacromolecules are polyphenols, which have traditionally been referred to as “vegetable tannins”, have recently been employed in engineering advanced materials, owing to their available physicochemical and biological properties and capability of assembly through diverse interactions. This thesis aims to introduce protein–polyphenol networks (PPNs), namely interconnected networks of proteins and polyphenols that can be deposited on a wide array of substrates. The polyphenol-mediated protein assembly of materials such as films, capsules, or nanoparticles (NPs) are introduced in this thesis because self-assembly approaches allow for the rapid generation of tailorable materials under mild conditions. This thesis also focuses on exploring the fundamentals of the interactions between proteins and polyphenols, which helps in understanding the assembly mechanism of PPNs. The binding affinity between polypeptides and polyphenols is studied by analytical chemistry techniques, focusing on the interactions between side chains of proteins and polyphenols, which is crucial for the controllable design of protein-based materials. Then, a straightforward and versatile strategy through interfacial polyphenol-mediated protein assembly is introduced to create a library of functional PPN materials, including bioactive surface coatings and functional capsules. Moreover, the PPN capsules not only can be used to clarify the governing interaction(s) between different proteins and polyphenols, but also can be employed in various applications (e.g., enzymatic catalysis, fluorescence imaging, and cell targeting). Next, a template-mediated supramolecular assembly method is developed to synthesize PPN NPs capable of endosomal escape and subsequent protein release in the cytosol. The versatility of this strategy in terms of NP size and protein type makes this a promising platform for potential applications in protein therapeutics. Finally, the protein–polyphenol interactions related to actual biological environments are investigated by the studying protein corona formed around different polyphenol-modified gold NPs (AuNPs). Protein corona compositional analysis demonstrates the binding preference of serum proteins with various polyphenols, and cellular uptake behaviors of polyphenol–AuNPs can elucidate the role of polyphenols in bio–nano interactions, which can act as reference works for the future implementation of polyphenols in biomedical applications.