This study examined the effect of environmental pH, gelatin backbone modification and crosslinking concentration on in vitro swelling/degradation kinetics and in vivo biocompatibility of gelatin-based hydrogels. Swelling/degradation studies showed that gelatin modified with polyethyleneglycol significantly increased the time to reach a maximum swelling ratio (T-max) and the time to degrade (T-fail), whereas gelatin modified with ethylenediaminetetraacetic dianhydride significantly increased T. Hydrogels crosslinked in 0.01 or 0.001% glutaraldehyde showed a significant difference in T-max and T-fail over gels crosslinked in 0.1% glutaraldehyde. The level of pH did not significantly affect the maximum swelling ratio (R-max), T-max the swelling ratio at failure (R-fail) or T-fail. In vivo studies showed that gelatin-based hydrogels elicited comparable levels of acute and chronic inflammatory response as that of the control by 21 d. Percent mass loss of samples increased with increasing implantation time and was further increased with decreasing percentage of glutaraldehyde fixation. We are currently quantifying the release kinetics of chlorhexidine from these hydrogels in vitro and investigating their potential use as a transplantation matrix for rat neural stem cells and as a drug carrier in mediating inflammation in vivo. By modulating the swelling/degradation and drug release kinetics and the in vivo biocompatibility, it is possible to develop a nonimmunogenic, bioresorbable cell/drug carrier matrix.
