Pb. Van Wachem et al., Tissue reactions to epoxy-crosslinked porcine heart valves post-treated with detergents or a dicarboxylic acid, J BIOMED MR, 55(3), 2001, pp. 415-423
Calcification limits the long-term durability of xenograft glutaraldehyde (
GA)-crosslinked heart valves. Previously, a study in rats showed that epoxy
-crosslinked heart valves reduced lymphocyte reactions to the same extent a
s the GA-crosslinked control and induced a similar foreign-body response an
d calcification reaction. The present study was aimed at reducing the occur
rence of calcification of epoxy-crosslinked tissue. Two modifications were
carried out and their influence on cellular reactions and the extent of cal
cification after 8 weeks' implantation in weanling rats was evaluated. Firs
t, epoxy-crosslinked valves were post-treated with two detergents to remove
cellular elements, phospholipids and small soluble proteins, known to act
as nucleation sites for calcification. The second approach was to study the
effect of the impaired balance between negatively and positively charged a
mino acids by an additional crosslinking step with a dicarboxylic acid. The
detergent treatment resulted in a washed-out appearance of especially the
cusp tissue. With the dicarboxylic acid, both the cusps and the walls had a
limited washed-out appearance. The wall also demonstrated some detachment
of the subendothelium. After implantation, both detergent and dicarboxylic
acid post-treatment histologically resulted in reduced calcification at the
edges of cusps and walls. However, total amounts of calcification, measure
d by atomic emission spectroscopy, were not significantly reduced. Data con
cerning the presence of lymphocytes varied slightly, but were in the same r
ange as the GA-crosslinked control, i.e., clearly reduced compared with a n
oncrosslinked control. It is concluded that both the double detergent and t
he dicarboxylic acid post-treatment of epoxy-crosslinked heart valve tissue
do not represent a sound alternative in the fabrication of heart valve bio
prostheses. (C) 2001 John Wiley & Sons, Inc.