Biomedical Engineering - Theses
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ItemThe dynamics and characterization of self-assembly in biopolymers and biosystems( 2020)Biological self-assembly is the foundation of the strength and elasticity which characterizes nature-derived biomaterials, including the cell’s architecture. Thus, an in-depth understanding of the mechanics behind this process can open the doors to various biomedical applications. For this purpose, this research employed novel experimental and characterization techniques to study self-assembly in biopolymers and biosystems. Initially, a droplet dissolution technique in liquid crystalline stages was used to analyze the process of self-assembly in two important biopolymers, silk and cellulose. Here, we report an effective and simple approach based on droplet dissolution in a liquid binary phase for the formation of silk fibroin transparent spheres as well as cellulose microbeads, both of which can span several hundred micrometers in diameter. The microstructure of the spheres formed at different ethanol concentrations was characterized by electron microscopy. High concentrations of ethanol caused droplets to be encased in a thin shell which collapses once it is taken out of the liquid phase. Generally, low ethanol concentrations produce transparent silk spheres and solid cellulose microbeads. This work on biopolymers demonstrates that controlled droplet dissolution self-assembling may be explored as a novel and effective way to tailor the microstructures of nature-derived biomaterials. The spheres generated in this manner have several different characteristics which can have multiple potential uses, such as templates for scaffolds, microcarriers, as well as photonics and nano-technological applications. The second part of this thesis investigated self-assembling in biosystems. Cell aggregates are an important tool in studying tissue remodelling, extracellular matrix formation, cell-cell interaction, and last but not the least, tissue-like biomechanical properties. A medium-throughput method was designed to characterize the mechanical properties of mesenchymal cell aggregates. This study was the first to present a precise and fast method to determine the Young’s modulus of mesenchymal cell aggregates, utilizing a step-by step aspiration technique. We were also able to recreate conditions that very closely resemble the in vivo environment, where the cells were found to be stretched, and the spheroids are soft and elastic Finally, potential applications of the self-assembled cell aggregates were explored in lung disease study and drug screening, specifically for Idiopathic Pulmonary Fibrosis (IPF). We demonstrated that the cell aggregates from IPF patients show an increase in stiffness, therefore mechanical testing of spheroids is an effective technique to study this disease. It was also found that a novel compound, PF670462, modulates the effect of TGF-beta and inhibits the fibrotic response of IPF cell aggregates. That is, this drug softens IPF spheroids and downregulates fibrogenic gene expression, therefore providing basis for the potential use of PF670462 in IPF treatment.