Study on Genipin: A New Alternative Natural Crosslinking Agent for Fixing Heterograft Tissue
In the field of cardiovascular surgery, there has been an effort to develop adequate prosthetic materials for cardiovascular reconstruction, such as vascular conduits, valve leaflets or patches for tissue defects. Until now, the biological materials made of bovine or porcine pericardium have been most widely used. These heterograft tissues must be biologically stable and safe in the human body, so they should be chemically modified or fixed to reduce immune or inflammatory reactions and to increase mechanical endurance and tolerance The ideal condition of heterografts for cardiovascular reconstruction is to be mechanically strong, tolerant of degeneration or calcification, easily manipulated by the surgeon's hand, and also less cytotoxic and immunological . Although several chemicals, including formaldehyde, glutaraldehyde, and epoxy compounds, that can fix biological tissue, glutaraldehyde has usually been used. Because many studies have been performed to evaluate the function, stability, and safety of glutaraldehyde as a fixing crosslinking agent, and to observe its long term use, there is sufficient clinical knowledge and experience on glutaraldehyde. However, glutaraldehyde still exhibits the drawbacks of high cytotoxicity and calicification, and we also lack knowledge on heterotopic immune response to it in the human body. Therefore, development of a new alternative fixation agent is required . For that reason, there have been attempts to use genipin, a natural crosslinking reagent, as a fixation material [
Genipin is an agent extracted from gardenia fruit (Gardenia jasminoides ELLIS). In traditional Chinese medicine, genipin has been used as a treatment for DM or jaundice patients. Many studies have reported on genepin's much lower level of cytotoxicity compared to glutaraldehyde
The aim of this study was to evaluate whether genipin could be used as an alternative crosslinking agent to glutaraldehyde for heterograft tissues. Thus, we compared the physical, biochemical, and histological characteristics of heterograft tissues (bovine pericardial tissues) fixed with genipin and those fixed with glutaraldehyde. As is generally known, the fixation of heterograft pericardial tissues with organic solvent causes permanent changes because it suppresses the nucleation of calcium phosphate and decreases the size and amount of collagen, which is assumed to enhance the mechanical durability of heterograft pericardial tissues
Therefore, we divided tissues into groups by concentration of genipin and the addition of organic solvent and observed changes in each tissue's characteristics to prepare clinically useful standards.
