| In this project, a series of hydrogel networks exhibiting significant changes in their swelling behavior in response to change in the external pH were prepared via different chemistries. These pH responsive hydrogel networks were formed based on formulations developed using hydrophilic polyether segments in combination with amine functional prepolymer(s) and were designed to swell and deliver needed agents to mammalian cells and stabilize the cell culture environment as triggered by a decrease in the pH. The polyether component of the network is sufficiently hydrophilic to give rise to some level of swelling independent of environmental pH, while the amine functional prepolymer(s) containing primary, secondary or tertiary amine groups, or a combination of all three, contribute towards the pH sensitivity of the network in the form of enhanced swelling and release under acidic conditions. The type and molecular weight of prepolymer and the reaction stoichiometry have been shown to control network formation and swelling and release characteristics in response to changes in pH. These various hydrogel formulations developed using different chemistries were tested and analyzed with specific focus on pH responsive water uptake, extractable fraction, swelling and release characteristics both in simple aqueous media and in mammalian cell culture. Several promising formulations developed in particular, those based on amine-epoxy addition chemistry, exhibited the desired pH responsive swelling behavior and demonstrated their ability to simultaneously neutralize lactic acid and release glucose in both cell-free culture media and mammalian cell culture, with no detectable evidence of cytotoxicity or changes in cell behavior in presence of SA-13 human hybridoma cells. Furthermore, a new experimental approach developed demonstrated a promising method to better understand the swelling and characterize the ionization behavior of these types of pH responsive hydrogels that opens new doors to determine previously unavailable data. |
