Dermal sheep collagen (DSC), which was crosslinked with 1,4-butanediol digl
ycidyl ether (BD) by using four different conditions, was characterized and
its biocompatibility was evaluated after subcutaneous implantation in rats
. Crosslinking at pH 9.0 (BD90) or with successive epoxy and carbodiimide s
teps (BD45EN) resulted in a large increase in the shrinkage temperature (T-
s) in combination with a clear reduction in amines. Crosslinking at pH 4.5
(BD45) increased the T-s of the material but hardly reduced the number of a
mines. Acylation (BD45HAc) showed the largest reduction in amines in combin
ation with the lowest T-s. An evaluation of the implants showed that BD45,
BD90, and BD45EN were biocompatible. A high influx of polymorphonuclear cel
ls and macrophages was observed for BD45HAc, but this subsided at day 5. At
week 6 the BD45 had completely degraded and BD45HAc was remarkably reduced
in size, while BD45EN showed a clear size reduction of the outer DSC bundl
es; BD90 showed none of these features. This agreed with the observed degre
e of macrophage accumulation and giant cell formation. None of the material
s calcified. For the purpose of soft tissue replacement, BD90 was defined a
s the material of choice because it combined biocompatibility, low cellular
ingrowth, low biodegradation, and the absence of calcification with fibrob
last ingrowth and new collagen formation. (C) 1999 John Wiley & Sons, Inc.