Preparation and fracture process of high strength hyaluronic acid hydrogels cross-linked by ethylene glycol diglycidyl ether

We present a synthetic strategy to produce high-strength hydrogels based on hyaluronic acid, a unique biomacromolecule with distinctive biological functions. The hydrogels were prepared using a two-step procedure. In the first step, hyaluronic acid (HA) was chemically cross-linked in aqueous solutions using ethylene glycol diglycidyl ether (EGDE) under various experimental conditions. EGDE-cross-linked HA hydrogels containing 97-99% water were fragile, and ruptured when compressed to 25-51% strain under 0.02-0.15 MPa stresses. By applying the double-network approach in the second step, we were able to generate high strength HA/poly(N,N-dimethylacrylamide) double-network hydrogels containing 84-94% water. Tuning the ratio of the network components could result in hydrogels exhibiting a compressive modulus of 0.9 MPa that sustain 19.4 MPa compressive stresses, which are much larger than those reported before for the hydrogels derived from the methacrylated HA macromers. Thus, the hydrogels presented here are promising materials to make use the characteristics of HA in stress-bearing biomedical applications. Cyclic mechanical tests show irreversible stress-strain curves with a large hysteresis indicating that elastically effective cross-links of HA first-network are irreversibly destroyed under load by dissipating energy. This internal fracture of HA network together with the high mass ratio of the second to the first-network components are responsible for the extraordinary mechanical properties of the hydrogels.