The chemical composition of glycosaminoglycan (GAG) hydrogels was found to have a profound effect on the physical properties of gels. Hyaluronan (HA) and chondroitin sulfate (CS) were each modified with adipic dihydrazide (ADH) with carbodiimide chemistry. The resulting polymer was crosslinked with various concentrations of poly(ethylene glycol) dialdehyde (PEG-diald) to produce a series of hydrogels. The physical properties of these GAG hydrogels varied in a concentration-dependent fashion. Maximal crosslinking was observed at a theoretical crosslinking of 50% for the HA-ADH-PEG-diald hydrogels and 75% for the CS-ADH-PEG-diald hydrogels. Adding PEG-diald beyond the optimum for crosslinking prolonged the in vitro enzymatic degradation time of the hydrogels. The swelling of the crosslinked GAG hydrogels was correlated with the amount of PEG-diald used rather than with the crosslinking density. (C) 2004 Wiley Periodicals, Inc.