Thermogelable PNIPAM microgel dispersion as 3D cell scaffold: effect of syneresis

Using poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)) microgel as an example, we proposed that thermogelable microgel dispersions can be used as a new type of injectable cell scaffolds. However, these in situ formed hydrogels shrink with time, which is undesirable for their use as cell scaffolds. In this work, the syneresis of hydrogels from poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions with various acrylic acid (AA) contents were measured. These concentrated microgel dispersions can all thermally gelate at physiological pH and ionic strength. With increasing AA content in the microgels, the gelation temperature of the dispersion increases, but the degree of syneresis of the resulting hydrogels decreases. The kinetics of shrinkage can be well described by the Tanaka-Fillmore equation, indicating that the deswelling of the hydrogels is governed by the cooperative diffusion of the gel network. These hydrogels present an interconnected porous structure with pore size decreases with an increasing degree of syneresis. HepG2 cells were seeded in these hydrogels. While the cells proliferate and form spheroid-like aggregates in hydrogels with a low degree of syneresis, their growth is inhibited in the one with a high degree of syneresis. These results indicate that the syneresis of the hydrogel has an adverse effect on cell culturing. This effect can be alleviated by adjusting AA content in the microgels. However, cells do not grow either if AA content is too high which results in a lack of cell-substrate interaction.