Frontiers in urethra regeneration: current state and future perspective.

Despite the positive achievements attained, the treatment of male urethral strictures and hypospadiases still remains a challenge, particularly in cases of severe urethral defects. Complications and the need for additional interventions in such cases are common. Also, shortage of autologous tissue for graft harvesting and significant morbidity in the location of harvesting present problems and often lead to staged treatment. Tissue engineering provides a promising alternative to the current sources of grafts for urethroplasty. Since the first experiments in urethral substitution with tissue engineered grafts, this topic in regenerative medicine has grown remarkably, as many different types of tissue-engineered grafts and approaches in graft design have been suggested and testedin vivo. However, there have been only a few clinical trials of tissue-engineered grafts in urethral substitution, involving hardly more than a hundred patients overall. This indicates that the topic is still in its inception, and the search for the best graft design is continuing. The current review focuses on the state of the art in urethral regeneration with tissue engineering technology. It gives a comprehensive overview of the components of the tissue-engineered graft and an overview of the steps in graft development. Different cell sources, types of scaffolds, assembling approaches, options for vascularization enhancement and preclinical models are considered.