Synthesis of methacrylated hyaluronic acid with tailored degree of substitution

The aim of this work was to develop a new method to derivatize hyaluronic acid (HyA) with polymerizable methacrylate residues with precise control over the substitution degree. The synthesis of methacrylated HyA (HyA-MA) was performed in dimethyl sulfoxide (DMSO) using glycidyl methacrylate (GMA) and 4-(N,N-dimethylamino)pyridine as a catalyst. HyA was rendered soluble in DMSO by exchanging the Na(+) ions by the more lipophilic tetrabutylammonium ions. HyA-MA with a fully controlled degree of substitution (DS, defined as the number of methacrylate groups per 100 disaccharide units), ranging from 5 to 30, was obtained at 50 degrees C after 48 h. Hydrogels were obtained upon radical polymerization of aqueous solutions of HyA-MA using potassium peroxodisulfate (KPS) as initiator and N,N,N ',N '-tetramethylethylenediamine (TEMED) as catalyst. Almost complete methacrylate conversion (95%) was achieved for hydrogels obtained by polymerization of HyA-MA with a degree of substitution of 15. At lower DS (DS 8.5 and 5) the methacrylate conversion was 82% and 68%, respectively. Rheological characterization showed that with increasing DS the storage modulus of these HyA-MA hydrogels increased. Swelling experiments showed that HyA-MA gels with a DS of 15 or above were dimensionally stable, whereas HyA-MA gels with DS 5 and DS 8.5 swelled 1.6 and 1.4 times their initial weight, respectively. In conclusion, this paper shows that the DS of HyA-MA can be tailored by the reaction conditions and that consequently HyA-MA hydrogels with different characteristics can be prepared. (c) 2007 Elsevier Ltd. All rights reserved.