NOVEL HYDROGELS OF HYALURONIC-ACID - SYNTHESIS, SURFACE-MORPHOLOGY, AND SOLID-STATE NMR

Hyaluronic acid (HA) is a linear polysaccharide consisting of repeating disaccharide units of N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcUA). A convenient methodology was recently developed that allowed the attachment of pendant hydrazido groups to the glucuronate moieties of hyaluronate oligosaccharides. This methodology was extended to high molecular weight hyaluronate (1.5 X 10(6)), and the products were cross-linked with four homobifunctional activated esters to give novel HA hydrogels. Solid-state C-13 NMR using cross-polarization and magic angle spinning (CP-MAS) revealed that the lyophilized native HA and hydrazido-HA retained solution-like structures in the solid state, The four HA hydrogels showed significant structural changes relative to native HA, and the carbon resonances of the cross-linkers were clearly evident. The surface morphologies of these cross-linked HA derivatives were examined using scanning electron microscopy (SEM). The electron micrographs of the freeze-dried hydrogels showed the presence of regular sheetlike structures forming pores (20-50 mu m). In contrast, native HA showed predominantly fibrous and irregular structures.