Mechanically strong hyaluronic acid hydrogels with an interpenetrating network structure

Abstract

Hyaluronic acid (HA) is a natural glycosaminoglycan of high molecular weight with important biological and physicochemical functions. Although hydrogels derived from HA are effective biomaterials for soft tissue regeneration, they are generally brittle, or require complicated synthetic procedures. A simple one-pot synthesis method of mechanically strong HA hydrogels would be attractive for many application areas. Here, we present preparation of HA hydrogels via free-radical copolymerization of methacrylated HA (GMHA) and N,N-dimethylacrylamide (DMA) in aqueous solutions. GMHA was synthesized by methacrylation of native HA at various levels of methacrylation between 4 and 25% corresponding to 115-721 pendant methacrylate groups per GMHA molecule. It was found that GMHA acts as a multifunctional cross-linker during its copolymerization with DMA leading to the formation of interpenetrated and interconnected polymer networks. The effective functionality of GMHA increases with its degree of methacrylation as well as with the DMA concentration. The viscoelastic and mechanical properties of HA hydrogels could be tuned by varying the degree of methacrylation of GMHA and DMA concentration. A significant improvement in the mechanical performance of the hydrogels was observed when DMA is replaced with methacrylic acid monomer. By adjusting the synthesis parameters, hydrogels with a Young’s modulus of around 200kPa could be prepared that sustain up to 20MPa stresses at 96% compression.