BACKGROUND: The use of bladder acellular matrix as a free graft to repair urethral defects and induce urinary tract regeneration has achieved certain results, but this method cannot fundamentally solve insufficient angiogenesis of the graft.
OBJECTIVE: To observe the effect of bladder acellular matrix (BAM) combined with vascular endothelial growth factor (VEGF) in the repair of rabbit urethral defects.
METHODS: Thirty adult New Zealand rabbits were randomly allocated into five groups (n=6 per group), including healthy control group, sham operation group, model group, BAM group, and BAM combined with VEGF group (VEGF-BAM group). Animal models of urethral defect were made in the latter three groups. The animals were sacri?ced at 4 and 12 weeks after surgery, respectively. The penis was immediately harvested for standardized passive ?owmetry, urethral radiography and subsequently ?xed for immunohistochemical staining for evaluation.
RESULTS AND CONCLUSION
: (1) The average urinary flow rate of the VEGF+BAM group was significantly higher than that of the model group and BAM group at 4 and 12 weeks after surgery (P
< 0.05), while there was no difference from the healthy control group and sham operation group. (2) Urethral radiography at 12 weeks after surgery indicated that urethra continuity was repaired with no urethral fistula in the VEGF+BAM group, but not incompletely in the model and BAM groups. (3) Hematoxylin-eosin staining results indicated there were more collagen fibers and infiltrated lymphocytes in the model group, with the fiber arrangement being disordered; the collagen matrix in the VEGF+BAM group was basically degraded, new collagen fibers arranged regularly, and there were many blood vessels, but no hemangioma; and in the BAM group, massive collagen deposition and less blood vessels were observed. (4) Masson staining results indicated that less collagen deposition was observed in VEGF+BAM group compared with BAM group and model group at 12 weeks after surgery (P
< 0.05), which was similar to the healthy control group and sham operation group (P
> 0.05). (5) CD31 staining results indicated that the local density of new blood vessels in the VEGF+BAM group was significantly higher than that in the BAM and models groups at 12 weeks after surgery (P
> 0.05), which was also close to the value in the healthy control and sham operation groups (P
> 0.05). (6) Regeneration of urethral smooth muscle in the VEGF+BAM group was significantly better than that in the BAM and model groups at 12 weeks after surgery (P
< 0.05), as indicated by a-SMA immunohistochemical staining. Moreover, there was no significant difference among VEGF+BAM group, sham operation group and health control group. To conclude, BAM scaffolds combined with VEGF show a totally potential capacity in inducing the urethral reconstruction. The combined use of VEGF and BAM can stimulate angiogenesis, decrease the rate of collagen deposition, promote urethral smooth muscle regeneration, and improve the urethra regeneration microenvironment in urethral reconstruction.