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  • Review Article
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Regenerative and engineered options for urethroplasty

Nature Reviews Urology volume 16, pages 453–464 (2019)Cite this article

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Abstract

Surgical correction of urethral strictures by substitution urethroplasty — the use of grafts or flaps to correct the urethral narrowing — remains one of the most challenging procedures in urology and is frequently associated with complications, restenosis and poor quality of life for the affected individual. Tissue engineering using different cell types and tissue scaffolds offers a promising alternative for tissue repair and replacement. The past 30 years of tissue engineering has resulted in the development of several therapies that are now in use in the clinic, especially in treating cutaneous, bone and cartilage defects. Advances in tissue engineering for urethral replacement have resulted in several clinical applications that have shown promise but have not yet become the standard of care.

Key points

  • Strategies to engineer the urethra mostly comprise two components — a scaffold to provide structure and cells to provide a barrier from transported fluids; growth factors can also be used to influence cell migration, graft remodelling and vascularization.

  • Several cell sources can successfully differentiate into urothelium, including urine, foreskin, oral mucosa and adipose tissue.

  • Urine-derived and adipose-derived stem cells have proved the most popular for urethral reconstruction owing to their low invasiveness of retrieval, ability to differentiate into different cell lineages, high proliferation potential and strong inhibition of the immune system.

  • Natural and synthetic scaffolds have been extensively investigated in urethral reconstruction, and the general consensus is that seeded patches are needed to successfully correct circumferential urethral defects >5 mm.

  • The first clinical studies using tissue-engineered scaffolds in the urethra showed encouraging results for the translation of these materials from the bench to the operating theatre, but further studies are needed to assess long-term outcomes.

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Fig. 1: The main players in urethral tissue engineering.
Fig. 2: The anatomy and histology of male urethra.

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Nature Reviews Urology thanks R. Santucci, A. Mundy and M. Lazzeri for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

    Filippo Pederzoli & Andrea Salonia

  2. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Filippo Pederzoli, Gregory Joice, Trinity J. Bivalacqua & Nikolai A. Sopko

  3. Università Vita-Salute San Raffaele, Milan, Italy

    Filippo Pederzoli & Andrea Salonia

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N.A.S. and F.P. researched data for the article and wrote the manuscript. All authors made substantial contributions to discussions of content and reviewed and edited the manuscript before submission.

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N.A.S. declares employment with PolarityTE. The other authors declare no competing interests.

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Pederzoli, F., Joice, G., Salonia, A. et al. Regenerative and engineered options for urethroplasty. Nat Rev Urol 16, 453–464 (2019). https://doi.org/10.1038/s41585-019-0198-y

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