Modulation of osteogenic activity of BMP-2 by cellulose and chitosan derivatives

Polysaccharides with structure and potential bioactivity similar to heparin were synthesized based on cellulose which was regioselectively sulfated, carboxylated or carboxymethylated, and chitosan that was sulfated only. Osteogenic activity of these derivatives was studied in cooperation with BMP-2 using C2C12 myoblast cells as a model system measuring alkaline phosphatase (ALP) activity and the expression of the genes Osterix, Noggin and Runx-2. It was found that highly sulfated chitosan showed the strongest osteogenic activity of all polysaccharides, but only at lower concentrations, while higher concentrations were inhibitory. By contrast, cellulose with a low or intermediate degree of sulfation showed increasing ALP activity and expression of Osterix and Noggin with rising concentrations. Lower sulfated cellulose with a high degree of carboxylation was less osteogenic, but had a positive effect on cell viability, while carboxymethylated cellulose had almost no osteogenic activity. The results indicate that regioselectively sulfated as well as carboxylated cellulose and chitosan possess an osteogenic activity, which makes them interesting candidates for application in tissue engineering of bone.