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The current state of tissue engineering in the management of hypospadias

Nature Reviews Urology volume 17, pages 162–175 (2020)Cite this article

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Abstract

Hypospadias is a congenital malformation resulting from the disruption of normal urethral formation with varying global prevalence. Hypospadias repair, especially that of proximal hypospadias (in which reconstruction of a long urethra is necessary), remains a surgical challenge despite more than two decades of surgical technique development and refinement. The lack of tissue substitutes with mechanical and biological properties similar to those of native urethra is a challenge for which the field of tissue engineering might offer promising solutions. However, the use of tissue-engineered constructs in preclinical studies is still hindered by complications such as strictures or fistulae, which have slowed progression to clinical application. Furthermore, the generation of uniform tubular constructs remains a challenge. Exciting advances in the application of nanotechnology and 3D bioprinting to urethral tissue engineering might present solutions to these issues.

Key points

  • Hypospadias is a common congenital abnormality with genetic, molecular and environmental causes that can result in functional or cosmetic issues for affected individuals.

  • Distal hypospadias repair is relatively successful, but complication rates of proximal hypospadias repair are high even for experienced surgeons despite surgical technique refinement.

  • Tissue engineering could address the lack of tissue substitutes with properties similar to those of native urethra for use in urethral reconstruction.

  • For hypospadias in particular, improved understanding of the mechanical properties and biological support being provided by the corpus spongiosum is needed.

  • Amongst the emerging tissue engineering technologies, nanotechnology could enable alteration of the microenvironment to improve wound healing and regeneration, and 3D bioprinting could be used to offer patient-tailored urethral constructs.

  • Scientific barriers, such as identifying the ideal tissue-engineered urethral construct, and practical barriers, including institutional support and funding for translational research, hamper clinical application of tissue-engineered constructs in hypospadias repair.

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Fig. 1: The meatal locations in varying degrees of hypospadias.
Fig. 2: Surgical management algorithm for hypospadias.
Fig. 3: Future applications of 3D bioprinting and nanotechnology in hypospadias repair.

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Acknowledgements

The authors thank S. Macomber who contributed to the production of the figures for this article.

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Authors and Affiliations

  1. Division of Pediatric Urology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Yvonne Y. Chan, Matthew I. Bury, Earl Y. Cheng & Arun K. Sharma

  2. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Emily M. Yura, Matthias D. Hofer, Earl Y. Cheng & Arun K. Sharma

  3. Simpson Querrey Institute, Northwestern University, Chicago, IL, USA

    Arun K. Sharma

  4. Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

    Arun K. Sharma

  5. Stanley Manne Children’s Research Institute, Chicago, IL, USA

    Arun K. Sharma

  6. Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, USA

    Arun K. Sharma

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Contributions

Y.Y.C., M.I.B., E.M.Y., M.D.H. and A.K.S. researched data for the article, Y.Y.C., E.Y.C. and A.K.S. made substantial contributions to discussion of content, Y.Y.C. wrote the manuscript and all authors reviewed and edited the article before submission.

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Correspondence to Arun K. Sharma.

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Nature Reviews Urology thanks W. Daamen, P. de Graaf and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Chan, Y.Y., Bury, M.I., Yura, E.M. et al. The current state of tissue engineering in the management of hypospadias. Nat Rev Urol 17, 162–175 (2020). https://doi.org/10.1038/s41585-020-0281-4

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