Autologous granulation tissue tubes for replacement of urethral defects: An experimental study in male rabbits

Tubularized urethroplasty is commonly performed in clinical practice using genital skin flaps, bladder mucosa, and buccal mucosa. However, the long-term effects are not satisfying, and donor site morbidities remain a problem. Besides, those grafts are unavailable with malignant conditions of the urinary tract, a history of lichen sclerosis, or oral disease.

An autologous granulation tissue tube of any required length and diameter can be produced by implanting foreign objects subcutaneously (Summary Fig.). The current study aimed to investigate to what extent of length this fully autologous tissue could be used for tubularized urethroplasty, satisfying urethral patency and tissue regeneration, in male rabbits.

Twenty-seven New Zealand male rabbits were randomly divided into three groups. Silastic tubes were implanted subcutaneously in Group 1 and Group 2. By 2 weeks the granulation tissue encapsulating the tubes was harvested. In Group 1, pendulous urethral segments of 1 cm were excised, and urethroplasty was performed with the granulation tissue tube in an end-to-end fashion. In Group 2, a pendulous urethral segment of 1.5 cm was replaced with the tissue tube. In Group 3, a pendulous urethral defect of 1 cm was repaired by re-anastomosis as control. Serial urethrograms were performed at 1, 2 and 6 months postoperatively. Meanwhile, the neo-urethra were harvested and analyzed grossly and histologically.

The urethrograms showed that all animals in Group 1 maintained a wide urethral caliber. In contrast, animals in Group 2 and Group 3 developed progressive strictures. Histologically, an intact urothelium with one to two cell layers lined the graft by 1 month, which was surrounded by increasing organized smooth muscle in Group 1. By 6 months, the grafts were completely integrated into native urethra. Nevertheless, extensive fibrosis occurred in Group 2 and Group 3.

The tissue successfully maintained patency and guided urethral regeneration across a distance of 1 cm. As an epithelium-free graft, the tissue showed better results than acellular matrix for tubularized urethroplasty compared with previous studies. Nevertheless, several limitations existed: (1) the urethral defect was created in healthy urethra, which could not fully simulate the clinical situation; (2) as a small animal model, rabbit was less informative for clinical problems; (3) the tissue was inadequate for long segmental urethral replacement. Further study is needed before the procedure is used clinically.

An autologous granulation tissue tube grown subcutaneously could be successfully used to repair urethral defects of 1 cm in male rabbits.