Crosslinkage of Collagen by Polyglycidyl Ethers

Abstract

Calcification is the principal cause of failure of glutaraldehyde treated bioprosthetic heart valves. This article reports the crosslinkage of several polyglycidyl ethers. Calcification of yak pericardium with polyglycidyl ethers was significantly decreased compared with that crosslinked with glutaraldehyde. The process of calcification of crosslinked yak pericardium was studied using 21 day subdermal implants in rats. The uptake of calcium with ethane diglycidyl ether was reduced (0.57 +/- 0.19 vs 4.28 +/- 1.62 micrograms/mg) over that with glutaraldehyde. Four polyglycidyl ethers were developed and compared. The best compound for raising the shrinkage temperature was the shortest chain compound without steric hindrance. In the polyglycidyl ether process, a suitable amount of alcohol was necessary to promote crosslinking; the catalyst, 2, 4, 6 -tris (dimethyl aminomethyl) phenol (TDAMP) and salicylic acid, were not favorable for long-term treatment of tissues because of the unnecessarily deep dyeing of the tissue, in addition to raising the shrinkage temperature. Unlike glutaraldehyde treatment, which reacts with lysine, polyglycidyl ether treated tissues maintained flexibility of the pericardial tissue, while binding amino acids such as lysine, methionine, tyrosine, aspartic acid and glutamic acid. The authors conclude that the ethane diglycidyl ether process combined with formaldehyde would further raise the shrinkage temperature from 78 degrees C to 87.5 degrees C and sustain it above 80 degrees C. Reverse treatment was not as effective. Compared with glutaraldehyde, polyglycidyl ether treatment renders tissue more flexible, increases the thermal stability of collagen, and decreases the incidence of calcification in vivo.