Tuning properties of injectable hydrogel scaffold by PEG blending

Abstract

We previously showed that poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions thermally gel under proper conditions and the in situ-formed hydrogels can be used for 3D cell culture. To further improve their performance, here we tailor the properties of the hydrogels by blending with poly(ethylene glycol) (PEG). The microgel/PEG mixtures containing no salt do not gel upon heating, however, they gel at physiological pH and ionic strength. The gelation temperature decreases with increasing PEG content, which was attributed to the decreased volume phase transition temperature of the microgel, and also depletion attraction because of the presence of PEG chains. Compared with the pure PNIPAM hydrogel, the blend hydrogels exhibit a lower mechanical strength (one-way ANOVA, P < 0.05), however, the syneresis of the hydrogel is reduced or even totally prevented by PEG blending. HepG2 cells were seeded and cultured in the blend hydrogels. While the cells do not grow in pure PNIPAM hydrogels, they grow very well in the blend hydrogel containing 0.75 wt% PEG (one-way ANOVA, P < 0.05), because of its reduced syneresis. Further increasing PEG content results in reduced cell–scaffold interaction, which in turn results in decreased cell growth rate. PEG content also influence the morphology of the multicellular spheroids formed inside the scaffold. Compact spheroids form in hydrogel containing 0.75 wt% PEG, while looser and smaller spheroids form in hydrogels with higher PEG content. Our results indicate physical blending can be a simple but effective method to finely tune the properties of injectable hydrogel scaffolds.