Investigation of the swelling behavior of crosslinked hyaluronic acid films and hydrogels produced using homogeneous reactions

Hyaluronic acid (HA) has been crosslinked in solution with glutaraldehyde (GTA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), poly(ethylene glycol) diglycidylether (EX 810), and divinyl sulfone (DVS) to form hydrogels. Flory-Rehner calculations were used to determine molecular weight between crosslinks (Mc), the crosslink density (Ve), and mesh size (ε) of crosslinked hydrogels after 24-h swelling in distilled water. Generally, lower molecular weight films gave rise to decreased molecular weights between crosslinks as well as increased effective crosslink densities and decreased mesh size. The effects of pH and salt concentration were evaluated. Use of lower molecular weight HA gave rise to decreased molecular weights between crosslinks as well as increased effective crosslink densities and decreased mesh size. Water diffusion coefficients were measured for DVS and GTA hydrogels and were found to be 1.4 x 10⁻¹⁰ and 1.8 x 10⁻¹⁰ m² s⁻¹. Autocrosslinked and HA polyethyleneimine gels were also produced but had very limited stabilities compared with the covalently crosslinked materials.