Relaxation and diffusion of water protons in BDDE cross-linked hyaluronic acid hydrogels investigated by NMR spectroscopy-Comparison with physicochemical properties

Cross-linked hyaluronic acid (HA) hydrogels are used in many biomedical applications but their characterization in order to distinguish between physicochemical properties is challenging. Longitudinal (T-1) and transverse (T-2) relaxation times and diffusion coefficient (D) of water protons in diepoxide 1,4-butanediol diglycidyl ether (BDDE)-cross-linked HA hydrogels were analyzed by high-field NMR spectroscopy to distinguish between different physicochemical properties. Hydrogels of different degrees of modification and cross-linking, representing a range of gel content, swelling ability, elastic and viscous behavior were studied, as well as solutions of native HA of different molecular weights. T-1, T-2 and D were measured for several concentrations of HA and as a function of temperature. D and T-1 showed a weak concentration dependence, but did not differ between the hydrogels. T-2, dominated by chemical exchange between water protons and exchangeable protons of HA, varied significantly between the different hydrogels and the temperature profiles changed dramatically between different concentrations.