In this study, we report the synthesis of a series of adaptive hydrogel networks prepared via different chemistries, exhibiting significant changes in their swelling behavior in response to change in the external pH. These pH responsive hydrogel networks were formed based on formulations developed using hydrophilic polyether segments in combination with amine functional prepolymer(s). The resulting networks 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 the external pH. Several promising networks developed in particular, those based on amine-isocyanate and amine-epoxy reaction, 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 SA-13 human hybridomas cells. Additionally, amine-isocyanate networks were also able to maintain the viability and pluripotency of embryonic stem cell cultures. Furthermore, pH was observed to have a clear effect on the rate at which glucose is released from the hydrogel network. Such characteristics promise to maintain a favorable cell culture environment in the absence of human intervention.