Comparison of poly(L-lactide-co-ε-caprolactone) and poly(trimethylene carbonate) membranes for urethral regeneration: an in vitro and in vivo study.

Abstract

Urethral defects are normally reconstructed using patient's own genital tissue; however, in severe cases, additional grafts are needed. We studied the suitability of poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(trimethylene carbonate) (PTMC) membranes for urethral reconstruction in vivo. Further, the compatibility of the materials was evaluated in vitro with human urothelial cells (hUC). The attachment and viability of hUCs and the expression of different urothelial cell markers (Cytokeratin 7, 8, 19 and Uroplakin Ia, Ib and III) were studied after in vitro cell culture on PLCL and PTMC. For the in vivo study, 32 rabbits were divided into the PLCL (n=15), PTMC (n=15) and control or sham surgery (n=2) groups. An oval urethral defect 1×2 cm in size was surgically excised and replaced with a PLCL or a PTMC membrane or urethral mucosa in sham surgery group. The rabbits were followed for 2, 4 and 16 weeks. After the follow-up, urethrography was performed to check the patency of the urethra. The defect area was excised for histological examination, where the epithelial integrity and structure, inflammation and fibrosis were observed. There was no notable difference on hUCs attachment on PLCL and PTMC membranes after 1 d of cell seeding, further, the majority of hUCs were viable and maintained their urothelial phenotype on both biomaterials. Postoperatively, animals recovered well, and no severe strictures were discovered by urethrography. In histological examination, the urothelial integrity and structure developed towards a normal urothelium with only mild signs of fibrosis or inflammation. According to these results, PLCL and PTMC are both suitable for reconstructing urethral defects. There were no explicit differences between the PLCL and PTMC membranes. However, PTMC membranes were more flexible, easier to suture and shape and developed significant epithelial integrity.