Tae, Giyoong (2002) In situ forming hydrogels using self-assembly of fluoroalkyl-ended poly(ethylene glycol)s. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-07192007-103729
Telechelic polymers with hydrophilic midblocks (poly(ethylene glycol), PEG) and hydrophobic end groups (fluoroalkyl, Rf) are synthesized and explored as candidates for in situ forming hydrogels for biomedical applications. Relevant physical properties, including phase behavior, rheology and erosion kinetics, are characterized to guide rational design of polymers for specific applications, including controlled release of therapeutic proteins and deposition of biocompatible surface layers. Disruption of the aggregation of the end groups using biocompatible complexing agents or solvents produces a low viscosity liquid that is injectable; self-assembly of the gel once inside the body can be achieved gently by diffusion of the complexing agent or solvent out into the surrounding tissue. By modulating molecular structure, the mechanical and erosion properties of these hydrogels can be systematically varied over a wide range for desired applications. With increasing fluoroalkyl length relative to PEG length, the phase behavior of these fluoroalkyl-ended PEGs (Rf-PEGs) polymers in aqueous solution changes from singlephase behavior (continuous transition in properties from solution-like to gel-like with increasing concentration), to sol-gel coexistence, to an insoluble precipitate (Chapter 2). For sol-gel coexisting polymers, the equilibrium gel concentration and the modulus of the gel phase are governed by the length of the PEG midblock, whereas the relaxation time is determined by the hydrophobe length. The erosion characteristics of these hydrogels correlate with their phase behavior: the gels of sol-gel coexisting species exhibit surface erosion in an open system with slow dissolution rate controlled by the end-group length, whereas gels showing single-phase behavior exhibit bulk erosion that is relatively fast. Aqueous solutions of Rf-PEGs exhibit ordering transitions, with increasing concentration (Chapter 3). The hydrophobic cores of the micelle-like aggregates order into a body-centered-cubic (BCC) structure. The aggregated state of the hydrophobic core is determined by the length of the hydrophobic end group, and is insensitive to the concentration of the polymer solution or the temperature. A shorter PEG length for a given end group produces a much enhanced ordering compared to a longer one. This micelle packing effect is manifested in changes in the viscoelastic properties: the single-relaxation behavior evolves to the appearance of a new low frequency elastic plateau in the dynamic moduli, and a linear response changes to a yielding behavior in creep. The gel phase of sol-gel coexisting polymers can be transformed into an injectable state by the addition of a bio-tolerable organic solvent, such as N-methyl pyrrolidone (NMP), and this solution can be restored to a hydrogel state quickly after injection by removal of the organic solvent by diffusion. Release of Human growth hormone (hGH) using this injectable formulation (Chapter 4) reveals that hGH remains stable inside the hydrogel formed, and more than 2 weeks of prolonged release of hGH pretreated with zinc is obtained using the injectable formulation without irreversible aggregation. For the Rf-PEGs examined here, the release rate of hGH is determined by the rate of diffusion through the hydrogel. The telechelic Rf-PEGs that exhibit sol-gel equilibrium or precipitated gel phase behavior provide a facile route to hydrophilic modification of poly(tetrafluoroethylene) (PTFE) surfaces that are frequently encountered in biomedical devices (Chapter 5). Dip coating of PTFE into 1 wt % Rf-PEGs in ethanol, followed by immersing into water, converts the surface of PTFE from hydrophobic to hydrophilic. The lifetime of this modification is correlated to the phase behavior of the bulk gel state, and stable in the various ranges of shear rates. An Rf-PEG that is insoluble in water gave a stable modification over a period of weeks in the absence of shear, and persisted for days when subjected to the highest shear stresses encountered in arteries (3-4Pa). Telechelic Rf-PEGs are effective, while monofunctional PEGs with a single fluoroalkyl group are not. The swelling and drying behaviors of thin films of RfPEGs (~0.1 [mu]m) show abnormalities relative to glassy and semi-crystalline films (Chapter 6). In a humidity ramp test starting from a dry state, thin films of Rf-PEGs show a distinctive hysteresis behavior; as humidity increases, little swelling occurs until ~ 85% humidity, then the film swells rapidly; as the humidity decreases, a rapid deswelling occurs near ~75% humidity. In a humidity step test, following a step-up the mass increase shows an overshoot, followed by a gradual approach to the equilibrium value, whereas the film tracks the equilibrium state very rapidly and monotonically following a step down from high to low humidity.
|Item Type:||Thesis (Dissertation (Ph.D.))|
|Degree Grantor:||California Institute of Technology|
|Division:||Chemistry and Chemical Engineering|
|Major Option:||Chemical Engineering|
|Thesis Availability:||Restricted to Caltech community only|
|Defense Date:||12 November 2001|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Imported from ETD-db|
|Deposited On:||20 Jul 2007|
|Last Modified:||12 Dec 2014 18:10|
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