Effect of vascular endothelial growth factor on regeneration of bladder acellular matrix graft: Histologic and functional evaluation

Abstract

Objectives To evaluate the effect of vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG). Methods A total of 40 female rats were divided into two groups. In the experimental group (VEGF+), the BAMG was incubated in VEGF and VEGF was injected into the host bladder. In the control rats, sterile solution replaced VEGF. Urodynamic studies were performed at grafting and repeated at 2, 4, 8, and 12 weeks. The bladders were harvested for histologic examination. Immunostaining was used to monitor VEGF treatment by examining VEGF and VEGF-receptor 2 expression. Neovascularity, smooth muscle induction, and nerve regeneration were assessed immunohistochemically. Results Increased VEGF and VEGF-receptor 2 were present in the VEGF+ rats 2 weeks after grafting. The maximal intravesical pressure was significantly greater in the VEGF+ group at 2 weeks than in the controls, despite the same bladder capacity. At 4 weeks, a significant increase in bladder capacity and a decrease in the postvoid residual volume ratio were observed. After 8 weeks, no differences were noted in the urodynamic parameters between the two groups. Numerous alpha-actin-positive spindle cells were observed in the VEGF+ rats at 2 weeks, and the smooth muscle content was significantly greater at all points. Enhanced angiogenesis was noted at 2 and 4 weeks. Nerve fibers were observed at 4 weeks and nerve growth factor-positive cells were significantly greater at 2, 4, and 8 weeks in the VEGF+ rats. Conclusions Administration of VEGF had significant effects on the BAMG at early periods after grafting. Our results have shown that VEGF enhances BAMG regeneration in rats as assessed by functional restoration and histologic examination.