Homologous acellular matrix graft for urethral reconstruction in the rabbit: Histological and functional evaluation

Objective: To evaluate urethral replacement by a free homologous graft of acellular urethral matrix in a rabbit model. Materials and Methods: In 30 male New Zealand rabbits, a 0.8 to 1.1 cm. segment of the urethra was resected, replaced with an acellular matrix graft of 1.0 to 1.5 cm. (mean 1.3 cm.), and placed on an 8F feeding tube. Additionally 4 animals underwent sham operation. At varying intervals before sacrifice (from 10 days to 8 months), the animals underwent urodynamic evaluation and retrograde urethrography (for which 4 untreated rabbits served as control). The grafted specimens were prepared for evaluation histologically and by reverse-transcription polymerase chain reaction (RT-PCR). Results: In all animals, the acellular matrix graft remained in its original position. Histological examination showed complete epithelialization and progressive vessel infiltration. At 3 months, smooth muscle bundles were first observed infiltrating the matrix at the end-to-end anastomosis; after 6 months, the smooth muscle bundles had grown into one-third of the matrix. Urodynamics did not detect any difference between the control and matrix-grafted animals in bladder volume, leak-point pressure and residual volume. RT-PCR detected an increase in IGF mRNA in the graft between week 3 and month 6 and in HB-EGF mRNA after day 10 through month 3. TGF-alpha mRNA was not detected; TGF-beta mRNA was unchanged from normal urethral tissue. By 8 months, the host and implant could not be differentiated by urethrography. Conclusion: The acellular urethral matrix allows single-stage urethral reconstruction. All tissue components were seen in the grafted matrix after 3 months, with further improvement over time; however, the smooth muscle in the matrix was less than in normal rabbit urethra and was not-well oriented. RT-PCR revealed the importance of time-dependent growth factor influences during regeneration.