Hydrogels with novel hydrolytically labile trehalose-based crosslinks: small changes - big differences in degradation behavior

Novel crosslinkers based on trehalose diacetals with acryloyloxy functionalities were synthesized and applied to the fabrication of degradable hydrogels with pH-dependent degradation characteristics at around physiological pH. Degradability at pH < 7 was ensured by the acetal group, while degradation at pH > 7 was caused by the ester group. The cleavage of hydrogels was monitored through the enzymatic determination of free trehalose released during hydrogel degradation. Analysis of the degradation products by 1 H NMR spectroscopy unambiguously confirmed that degradation of the acetal moiety in acidic solutions proceeded without affecting the ester moiety, while cleavage of the ester entity in alkaline solutions occurred without affecting the acetal group. Further studies showed that the degradation rate of hydrogels was strongly influenced by the acrylamide-type monomer selected for hydrogel preparation. Novel crosslinkers based on trehalose diacetals were synthesized and applied to the fabrication of degradable polyacrylamide-type hydrogels with pH-dependent degradation characteristics at around physiological pH.