Long-term histological results following glutaraldehyde cross-linked collagen injection into the suburothelial space of the mini-pig bladder

Abstract

Endoscopic correction of vesicoureteric reflux by subureteric injection has become an accepted method of treatment in selected cases. Its efficacy has been demonstrated in the treatment of well over 1,000 ureters. However, there are doubts as to the long-term safety of the commonly injected substance Teflon. Glutaraldehyde cross-linked bovine collagen, a biodegradable substance, was suggested as an alternative material for injection. The aim of this study was to evaluate the histological long-term behavior of glutaraldehyde cross-linked bovine collagen injected into the mini-pig bladder. One hundred and eight deposits of cross-linked collagen, each containing 0.2 ml (n = 36) or 0.6 ml (n = 72) collagen paste, were injected into the suburothelial space of the bladders of 24 mini-pigs. The histological behavior of the implants was studied at monthly intervals over a period of 12 months. After only 2 months a marked invasion of host fibroblasts and formation of endogenous type I and III collagen could be observed. Over 12 months the invasion of fibroblasts and the formation of new collagen increased dramatically. No migration of collagen particles into the local lymphatic system could be observed. A new staining technique (solophenyl red 3BL) was introduced to selectively demonstrate type I and III collagen fibres. In addition, the efficacy of the subureteric collagen injections could be demonstrated by successfully treating reflux that was iatrogenically induced in the mini-pig bladders.