Several groups have attempted urethral substitution using TE cell-free matrices, such as bladder acellular matrix graft (BAMG) and small intestinal submucosa (SIS) or cellularised matrices
[26][27][28][29][30][31][32][33]. These matrices are prepared from native tissues by decellularising and sterilising them. As shown in rabbits by Dorin et al., a significant problem of acellular matrices is that urothelial regeneration is limited to 0.5 cm, which compromises success in more complex cases, such as long strictures
[34]. Synthetic polymers have also shown advantages (poly-l-lactic acid, (PLLA) and poly(lactic-co-glycolic) acid, (PLGA)) for forming low-cost, biocompatible, three-dimensional (3D) organs with controlled mechanical properties. However, synthetic scaffolds without functionalisation by peptides do not allow the proper differentiation of epithelial cells into well-organised tissue. Indeed, contrarily to natural matrices, they cannot recreate the target organ microenvironment, especially adequate ECM-cell interaction (e.g., lack integrin-binding peptide sequence, failure in synchronisation between degradation rate and matrix neo-deposition)
[13][35][36]. No long-term experiment has been performed with a significant number of patients. Currently, protocols developed are not used in clinics despite the media coverage of some, signalling the immaturity of the works, which must continue to be improved
[37]. TE substitutes that contain autologous cells in addition to an extracellular matrix, close to the native one, are more promising. The main advantage of this method is that a large graft of autologous cells can be produced with a limited sample, such as a piece of oral or bladder mucosa. Indeed, the extracted cells can be grown in vivo, seeded on the biomaterial and implanted with a very low risk of rejection. Studies have also reported that stem cells can be obtained from urine, making this approach potentially useful
[38][39]. A downfall of this method is that after long periods of culture to obtain well-differentiated tissues, the exogenous matrices become challenging to manipulate and lose their mechanical and physical properties. Despite significant progress in urethral TE, very few teams have performed clinical trials and published their results to date
[40] (
Table 1). However, the four clinical trials conducted to date show promising results in a limited number of patients with long-segment and/or complex stenosis
[37][41][42][43][44]. While these models are certainly far from a “plug and play” alternative with consistently reproducible results, they could offer an alternative for complex cases requiring long segment urethral replacement
[45].