Injectable self-assembling hydrogel from alginate grafted by P(N-isopropylacrylamide-co-N-tert-butylacrylamide) random copolymers

Sodium alginate grafted by a thermo-responsive copolymer of N-isopropylacrylamide, enriched with the hydrophobic N-tert-butylacrylamide monomer, (P(NIPAM-co-NtBAM)-NH2) was synthesized and its thermo- and shear-induced responsive capabilities were studied through rheology. The graft copolymer formed a 3D network through thermo-induced hydrophobic association of the thermo-responsive P(NIPAM-co-NtBAM) side chains in water. By applying the frequency-temperature superposition principle, the terminal relaxation time, tau and the shear viscosity, as a function of temperature were evaluated. Both parameters increased exponentially upon heating orders of magnitude, 15 degrees C above the onset of gelation (35 degrees C). It is shown that the thermo-induced thickening effect was mainly due to the slowdown of the P(NIPAM(90)-co-NtBAM(10)) associative side chains exchange dynamics. Moreover, combination of shear- and thermo-responsiveness provided excellent hydrogel injectability with instantaneous gelation at physiological temperature. The better insight of the thermo-thickening mechanism through oscillatory rheology allows precise tuning of the carbohydrate-based hydrogel properties towards potential bioapplications.