In this study, we synthesized and characterized a series of macromers based on poly( N-isopropylacrylamide) that undergo thermally induced physical gelation and, following chemical modification, can be chemically cross-linked. Macromers with number average molecular weights typically ranging from 2000-3500 Da were synthesized via free radical polymerization from, in addition to N-isopropylacrylamide, pentaerythritol diacrylate monostearate, a bifunctional monomer containing a long hydrophobic chain, acrylamide, a hydrophilic monomer, and hydroxyethyl acrylate, a hydrophilic monomer used to provide hydroxyl groups for further chemical modification. Results indicated that the hydrophobic-hydrophilic balance achieved by varying the relative concentrations of comonomers used during synthesis was an important parameter in controlling the transition temperature of the macromers in solution and stability of the resultant gels. Storage moduli of the macromers increased over 4 orders of magnitude once gelation occurred above the transition temperature. Furthermore, chemical cross-linking of these macromers resulted in gels with increased stability compared to uncross-linked controls. These results demonstrate the feasibility of synthesizing poly( N-isopropylacrylamide)-based macromers that undergo tandem gelation and establish key criteria relating to the transition temperature and stability of these materials. The data suggest that these materials may be attractive substrates for tissue engineering and cellular delivery applications as the combination of mechanistically independent gelation techniques used in tandem may offer superior materials with regard to gelation kinetics and stability.

Stimulus responsive materials hold great promise in biological applications as they can react to changes in physiological stimuli to produce a desired effect. Stimulus responsive macromers designed to respond to temperature changes at or around 37 °C and the presence of divalent cations were synthesized from N-isopropylacrylamide, pentaerythritol diacrylate monostearate, 2-hydroxyethyl acrylate, and vinylphosphonic acid by free radical polymerization. Monomers were incorporated into the macromers in ratios approximating the molar feed ratios, and macromers underwent thermogelation around normal body temperature (36.2 -40.5 °C) as determined by rheology and differential scanning calorimetry. Macromers containing vinylphosphonic acid interacted with calcium ions in solution, displaying decreased sol-gel transition temperatures (27.6 -34.4 °C in 100 mM CaCl 2 ), with decreases of greater magnitude observed for macromers with higher relative vinylphosphonic acid content. Critical micellar concentrations also decreased in a dose-dependent manner with increased vinylphosphonic acid incorporation in solutions with CaCl 2 but not in solutions with NaCl. These dually responsive macromers allow examination of the effect of increasing vinylphosphonic acid content in a macromer which holds promise in biological applications such as drug and cell delivery or tissue engineering due to the macromer responsiveness at physiological temperatures and concentrations of calcium.