Novel Cellulose Derivatives with Mitogenic and Osteogenic Activity

Abstract

Cellulose was sulfated by different routes to obtain cellulose sulfates (CS) with diverse degrees of sulfation (DSS). Lower sulfated celluloses were either carboxylated at 6-O-position through a TEMPO-mediated oxidation or carboxymethylated at all hydroxyl groups (2-O, 3-O and 6-O-position) by chloroacetic acid. The chemical structure of products was characterized via elemental analysis, 13C NMR and FT Raman spectroscopy, while the average degree of polymerization (DP) was studied using size exclusion chromatography. The bioactivity of these derivatives was studied towards their interactions with growth factors FGF-2 and BMP-2 having either a mitogenic/angiogenic or osteogenic activity, respectively. Competitive binding experiments showed an increase of binding of FGF-2 to CS with rising DSS, but lower than heparin. No such dependency was observed for the carboxylated or carboxymethylated derivatives. Binding experiments with BMP-2 showed that CS with intermediate DSS had superior binding, although some binding was observed with carboxymethylated CS, too. Cell culture experiments exhibited a mitogenic effect for higher sulfated celluloses, but not for carboxy(methylated) CS. Osteogenic activity measured by expression of alkaline phosphatase showed high effect for CS with intermediate DSS and moderate for carboxylated and carboxymethylated CS. Overall, these cellulose derivatives possess a cooperative activity with heparin-binding growth factors, which is highly dependent on the degree of derivatisation and type of functional groups.