Submitted to the Department of Chemical Engineering.
Thesis (Ph.D.)--Stanford University, 2013.
Hydrogel networks have long been studied for their highly tunable properties that make them attractive as biomaterials for such applications as tissue engineering and drug delivery. As water-swollen polymer networks held together by chemical or physical crosslinks, hydrogels are notably responsive to changes in their chemical composition and method of network formation. Processing of the polymer network after synthesis can be equally important to hydrogel properties due to the environmental sensitivity of many polymers to changes in solvent, pH, and temperature. Understanding the effects of hydrogel composition and processing on the resulting network structure and properties is necessary for rational design of functional hydrogels for specific applications. This work examines the influence of composition and processing on the structure/property relationship of hydrogel networks constructed from poly(ethylene glycol) (PEG), a common biopolymer. The basic PEG hydrogel is fabricated via photopolymerization of PEG macromonomers to create an end-linked swollen network with weakly ordered, dense, hydrophobic crosslink junctions. Composition and processing modifications alter the PEG network structure, which was explored using small angle x-ray scattering (SAXS). Such morphological alterations translate to changes in the macroscopic hydrogel properties, such as network swelling, molecular transport, and mechanical response to deformation. This behavior was analyzed through several adaptations to the PEG hydrogel network including addition of network defects, variation of PEG concentration, network synthesis in organic solvent, insertion of an interpenetrating poly(acrylic acid) (PAA) network, incorporation of tethered cholesterol, and network formation with an amphiphilic template. Diffusion coefficients of globular proteins within PEG hydrogels increased linearly with hydrogel swelling, which responded to variation in the network crosslink density. Accordingly, the most permeable PEG hydrogels consisted of a low concentration of longer PEG macromonomers. Network defects caused by inefficient PEG functionalization were determined to be a significant contributing factor to the structural expansion that facilitated protein diffusion. Investigation of PEG networks prepared in water versus chloroform revealed that differences in the PEG chain conformation during network synthesis are transferred to the equilibrium-swollen hydrogels. PEG network morphology depended on the precursor concentration regime, and this was influenced by the semidilute-concentrated crossover concentration, which is higher in chloroform. Both structure and mechanical properties of corresponding PEG/PAA double networks depended on the PEG precursor conditions rather than the PEG hydrogel equilibrium environment. PEG networks made in chloroform had fewer entanglements and were more easily stretched by the interpenetrating, ionic PAA network. Incorporation of PEG-tethered cholesterol (PEG-chol) into a PEG network via synthesis in organic solvent resulted in the formation of self-assembled cholesterol aggregates when the networks were transferred to water for equilibrium swelling. At lower ratios of PEG-chol to PEG containing < 12 wt% cholesterol among the total solids, cholesterol aggregated into the weakly ordered PEG network crosslinks. Upon further addition (12-20 wt% cholesterol), cholesterol self-assembled into polydomains of lamellar-like meso-ordering. Structural transitions were reflected in the swelling and mechanical properties. The presence of physical crosslinks in addition to chemical crosslinks enhanced the elastic modulus while reducing material brittleness upon deformation. PEG network formation in the presence of self-assembled amphiphilic polymers clearly demonstrated the impact of composition and processing on the resulting hydrogel morphology. When amphiphilic block copolymers were introduced into PEG precursors, they acted as a template to create lamellar meso-ordered domains within the network. The physically assembled block copolymers could be washed out of the hydrogel without interrupting the lamellar ordering. In contrast, PEG-chol self-assembled into micelles in aqueous solvent that were chemically attached to the PEG network upon photopolymerization. Processing of the resulting hydrogels via swelling, de-swelling, or solvent exchange altered the original structural ordering.