| dc.description.abstract | Today, custom-tailored polymeric hydrogel microparticles are routinely used for drug delivery, medical diagnostics, as well as many fundamental studies in colloidal science. There is growing consensus that physical attributes, such as size, shape, internal structure, and mechanical deformability, of the particles can influence material performance, especially when they are placed into a biological setting. Over the past two decades, a host of particle fabrication techniques have been proposed, which are able to produce microgels with various physical properties, though maintaining independent control over them remains to be difficult. This thesis explores the synthesis of a new class of functional microparticles bearing the likeness of mammalian cells through the use of a new microfluidics-based lithography process, and demonstrates the utility of these biomimetic microparticles in novel biomedical applications. First, we devise a microscope projection technique based on stop-flow lithography (SFL), which allows free-standing microparticles of any arbitrary 2D-extruded, mask-defined shape to be patterned down to the cellular size regime (>/= 10 [mu]m) from UV-crosslinkable oligomer formulations in a semi-continuous fashion. By modulating the degree of oxygen inhibition during synthesis, we achieve previously unattainable particle sizes. Brownian diffusion of colloidal discs in bulk suggests the out-of-plane dimension can be as small as 0.8 [mu]m, which agrees with confocal microscopy measurements. We measure the hindered diffusion of microdiscs near a solid interface and compared our results to theoretical predictions. These biocompatible colloidal particles can also flow through physiological microvascular networks formed by endothelial cells undergoing vasculogensis under minimal hydrostatic pressure. Second, inspired by the hierarchical structure of eukaryotic cells, we synthesize composite microparticles containing a homogenous distribution of hydrophobic compartments from crosslinkable silicone oil-in-water nanoemulsions. The nanoemulsion loadings achieved in our composite microgels have, to our knowledge, among the highest ever demonstrated in a hydrogel material. In addition, we perform proof-of-concept assays to show several orthogonal motifs, such as tunable hydrophobic anchoring at the oil/water interface and matrix degradation at high pH, by which both hydrophobic and hydrophilic compounds, including small molecules, proteins and the nanoemulsion droplets themselves, can be effectively encapsulated in and released from the resulting microparticles over a wide range of timescales. And last, we fabricate red blood cell-mimicking, oxygen-carrying composite microparticles from perfluorocalin-in-water nanoemulsions. Unlike silicone oil nanoemulsions, the PFD-based formulations require osmotic stabilization due to a finite solubility of oil in the aqueous continuous phase. The presence of perfluorocarbon oil droplets increases the solubility and diffusivity of oxygen in the prepolymer solution, thereby enhancing the rate of O₂ inhibition during microparticle synthesis. We develop a simple model that successfully predicts the augmented O₂ mass transport, which agrees well with experimental data. Encapsulating nanodroplets in the hydrogel network allows us to generate and preserve small droplets under nearly surfactant-free conditions via quick washing steps post-synthesis. | en_US |
