Genipin‐crosslinked chitosan hydrogels: Preliminary evaluation of the in vitro biocompatibility and biodegradation

Genipin-crosslinked chitosan hydrogels have gained attention as promising drug delivery vehicles. To bring them one step closer to clinical applications, this study evaluates the hydrogels' in vitro biocompatibility and biodegradation. Cytotoxicity test on 3T3 fibroblasts shows that the cells retain normal adhesive properties and high viability on gels with 3.1 and 4.4 mm genipin but not on gels with 1.7 mm genipin. The hydrogels with highest genipin content (4.4 mm) are studied further in the presence of RAW 264.7 macrophages and DC 2.4 dendritic cells. In both cases, cell viability is preserved and interferon-β gene transcription is enhanced while over-production of five inflammatory cytokines is not detected, suggesting the hydrogels' immune stimulating property and potential as vaccine carriers. The biodegradation is monitored efficiently using the hydrogels' intrinsic fluorescence upon crosslinking with genipin. Addition of poly (ethylene glycol) to form a semi-interpenetrating hydrogel is found to enhance the cytocompatibility to 3T3 cells and delay the degradation. Collectively, our findings suggest that chitosan-genipin hydrogels can be considered as biocompatible materials, with great potential for vaccine delivery applications.