BIOCOMPATIBILITY STUDY OF A BIOLOGICAL TISSUE FIXED WITH A NATURALLY-OCCURRING CROSS-LINKING REAGENT

A recognized disadvantage of the currently available chemical reagents used to fix bioprostheses is the potential toxic effects a recipient may be exposed to from residues. It is therefore desirable to provide a crosslinking reagent that is of low cytotoxicty and can form stable and biocompatible crosslinked products. To achieve this goal, a natura lly occurring crosslinking reagent-genipin-was used by our group to fi x biological tissues. Genipin can be obtained from its parent compound geniposide, which can be isolated from the fruits of Gardenia jasmino ides ELLIS. In our previous feasibility study, it was found that the c ytotoxicity of genipin is significantly lower than both glutaraldehyde and an epoxy compound. Additionally it was shown that genipin can for m stable crosslinked products. The present study further investigates the biocompatibility of a genipin-fixed porcine pericardium implanted subcutaneously in a growing rat model. The fresh, glutaraldehyde-, and epoxy-fixed counterparts were used as controls. It was noted that the inflammatory reaction of the genipin-fixed tissue was significantly l ess than its glutaraldehyde- and epoxy-fixed counterparts. Also, the g enipin-fixed tissue has tensile strength and resistance against in viv o degradation comparable to the glutaraldehyde-fixed tissue. Additiona lly, the calcium content of the genipin-fixed tissue measured througho ut the entire course of the study was minimal. Nevertheless, further s tudy in calcification for the genipin-fixed tissue should be conducted in a blood-contact environment. The results obtained in this subcutan eous study indicate that genipin is a promising crosslinking reagent f or biological tissue fixation. However, further durability testing in vitro and in vivo are needed to determine the relative functional meri ts of this new crosslinker. (C) 1998 John Wiley & Sons, Inc.