HEPATOCYTE CULTURE ON CARBOHYDRATE-MODIFIED STAR POLYETHYLENE OXIDE HYDROGELS

We describe the synthesis and in vitro biological characterization of a new class of carbohydrate-modified hydrogels based on radiation-cros s-linked star polyethylene oxide (PEG). Hydrogels were synthesized fro m either of two types of PEO star molecules in order to vary the termi nal hydroxyl content of the gels while keeping other gel properties su ch as molecular weight between cross-links and water content constant. The resulting gels were covalently modified with monosaccharide ligan ds and the behaviour of primary rat hepatocytes on the modified gels w as evaluated under culture conditions. Hepatocytes exhibited a sugar-s pecific adhesion to the modified gels, adhering to gels bearing galact ose but not glucose. Cell spreading was observed on both types of gala ctose-modified PEO star gels; moreover, the gels supported long-term ( 6 d) culture and differentiated function of primary hepatocytes. Furth er, on comparing the cell spreading behaviour observed on the PEO star gels with that reported previously for galactose-modified polyacrylam ide, we find that our gels elicit spreading at ligand concentrations l ower by an order of magnitude. A simple mechanistic analysis indicates that this enhanced ability of PEO star gels to support spreading of p rimary hepatocytes on low concentrations of immobilized galactose deri ves from freedom of the immobilized ligands to come within sufficientl y close proximity to mimic a high-affinity branched oligosaccharide.