Injectable hydrogels based on alginates grafted with LCST side-chains of different chemistry

A homologous series of thermoassociating copolymers was prepared by grafting onto alginates different amounts of three different temperature responsive polymers: poly(N-isopropylacrylamide), poly(di(ethylene glycol)methacrylate) and poly(ethylene oxide-co-propylene oxide). From a large set of analytical techniques combining rheology, calorimetry, NMR and SAXS, the relevant parameters controlling the sol/gel transition and the gel properties, mainly the degree of entanglement of macromolecules and the fraction of responsive stickers, were highlighted and interpreted objectively by considering the particularities of the phase diagrams of LCST polymers. Complementary analyses were implemented to investigate adhesiveness, injectabilty, gel swelling and molecular release in physiological environment of thermogelling formulations. In particular, it is shown that steady shear experiments allow to predict the injection forces by taking into account the characteristics of the system (syringe and needle), and that the rapid gelation of the formulations when they are heated at 37 °C delays the release of small molecules into the environment. The overall set of data is discussed in the framework of scaling relations in order to draw quantitative guidelines for the design of injectable thermoresponsive hydrogels.