Crosslinking structures of gelatin hydrogels crosslinked with genipin or a water‐soluble carbodiimide

Abstract

It was suggested in our previous studies that carbodiimide-and genipin-crosslinked gelatin hydrogels could be used as bioadhesives to overcome the cytotoxicity problem associated with formaldehyde-crosslinked gelatin hydrogels. In this study, we investigated the crosslinking structures of carbodiimide-and genipin-crosslinked gelatin hydrogels. We found that crosslinking gelatin hydrogels with carbodiimide or genipin could produce distinct crosslinking structures because of the differences in their crosslinking types. Carbodiimide could form intramolecular crosslinks within a gelatin molecule or short-range intermolecular crosslinks between two adjacent gelatin molecules. On the basis of gel permeation chromatography, we found that the polymerization of genipin molecules could occur under the conditions used in crosslinking gelatin hydrogels via a possible aldol condensation. Therefore, besides intramolecular and short-range intermolecular crosslinks, additional long-range intermolecular crosslinks could be introduced into genipin-crosslinked gelatin hydrogels. Crosslinking a gelatin hydrogel with carbodiimide was more rapid than crosslinking with genipin. Therefore, the gelation time for the carbodiimide-crosslinked gelatin hydrogels was significantly shorter than that of the genipin-crosslinked gelatin hydrogels. However, the cohesive (interconnected) structure of the carbodiimide-crosslinked gelatin hydrogels was readily broken because, unlike the genipin-crosslinked gelatin hydrogels, there were simply intramolecular and shortrange intermolecular crosslinks present in the carbodiimidecrosslinked hydrogel. In the cytotoxicity study, the carbodiimide-crosslinked gelatin hydrogels were dissolved into small fragments in the cultural medium within 10 min. In contrast, the genipin-crosslinked gelatin hydrogels remained intact in the medium throughout the entire course of the study. Again, this may be attributed to the differences in their crosslinking structures. The genipin-crosslinked gelatin hydrogels were less cytotoxic than the carbodiimidecrosslinked gelatin hydrogels.

Preparation, Characterization and Properties of Films Obtained from Cross-linked Guar Gum

“…The cross-linking process in films generally increases the TS and decreases the percentage of elongation. However, the opposite behavior observed in our case for the GG/EDC system is in agreement with results reported for other polysaccharide and protein systems [23,45] . The EDC interacts with hydroxyl groups from the backbone or from the galactose side group, blocking the hydrogen bonding sites on the guar gum and consequently reducing the intermolecular interactions between the polymer molecules.…”

“…Carbodiimides have been used, for example, to cross-link blends of collagen and polyvinyl alcohol and shown to be more efficient in the release of a growth hormone than the same system cross-linked with glutaraldehyde [22] . Liang et al [23] studied hydrogels of gelatin cross-linked with EDC and genipin lattices. The authors observed that carbodiimides can form intra-and intermolecular bonds in gelatin.…”

Genipin-crosslinked gelatin microspheres as a strategy to prevent postsurgical peritoneal adhesions: In vitro and in vivo characterization

“…Spontaneous reaction of genipin as azaphilone with an amino group forms a nitrogen-iridoid which undergoes dehydration to form an aromatic monomer [45] . Others speculate that genipin molecules may be polymerized before crosslinking with amino groups [31] .…”

Genipin-Crosslinked Gelatin-Based Emulgels: an Insight into the Thermal, Mechanical, and Electrical Studies

“…Genipin is a naturally occurring crosslinker obtained from the fruits of Gardenia jasminoides. It has been gaining importance in biomedical industries due to its far less cytotoxic nature as compared with glutaraldehyde (10,11).…”