The synthesis of a series of thermo-responsive ABA triblock copolymers in which the outer A blocks comprise poly(2-hydroxypropyl methacrylate) and the central B block is poly(2-(methacryloyloxy)ethyl phosphorylcholine) is achieved using atom transfer radical polymerization. These novel triblock copolymers form thermo-reversible physical gels with critical gelation temperatures and mechanical properties that are highly dependent on the copolymer composition and concentration. TEM studies on dried dilute copolymer solutions indicate the presence of colloidal aggregates, which is consistent with micellar gel structures. This hypothesis is consistent with the observation that incorporating a central disulfide bond within the B block leads to thermo-responsive gels that can be efficiently degraded using mild reductants such as dithiothreitol (DTT) over time scales of minutes at 37 degrees C. Moreover, the rate of gel dissolution increases at higher DTT/disulfide molar ratios. Finally, these copolymer gels are shown to be highly biocompatible. Only a modest reduction in proliferation was observed for monolayers of primary human dermal fibroblasts, with no evidence for cytotoxicity. Moreover, when placed directly on 3D tissue-engineered skin, these gels had no significant effect on cell viability. Thus, we suggest that these thermo-responsive biodegradable copolymer gels may have potential applications as wound dressings.

The synthesis of a series of amphiphilic AB diblock copolymers in which the A block comprises poly(2-(methacryloyloxy)ethyl phosphorylcholine) [PMPC] and the B block comprises poly(2-hydroxypropyl methacrylate) [PHPMA] by atom transfer radical polymerization (ATRP) is reported. The aqueous solution properties of these new diblock copolymers were examined using dynamic light scattering and variable temperature (1)H NMR spectroscopy. Copolymers with shorter thermoresponsive PHPMA blocks formed relatively large aggregates, while copolymers with longer PHPMA blocks formed smaller aggregates. This apparently "anomalous" self-assembly behavior occurs because the PHPMA block becomes more hydrophobic as its degree of polymerization is increased. Therefore, shorter PHPMA blocks lead to the formation of loose highly hydrated aggregates, whereas longer blocks formed more compact dehydrated aggregates. In addition, these new PMPC-PHPMA diblock copolymers are highly biocompatible and can mediate the relatively rapid efficient uptake of a fluorescent dye by human dermal fibroblast cells. Interestingly, dye uptake kinetics appear to depend on the hydrophobic/hydrophilic balance of the copolymer. This not only bodes well for in vitro imaging of live cells for biomedical applications but also highlights the importance of copolymer design to ensure efficient drug delivery.

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