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Platinum Priority – Review – Reconstructive Urology

Editorial by Karl-Dietrich Sievert on pp. 607–609 of this issue

Tissue Engineering of the Urethra: A Systematic Review and

Meta-analysis of Preclinical and Clinical Studies

Luuk R.M. Versteegden

a , y

, Paul K.J.D. de Jonge

b ,

y

, Joanna IntHout

c ,

Toin H. van Kuppevelt

a ,

Egbert Oosterwijk

b ,

Wout F.J. Feitz

b , d ,

Rob B.M. de Vries

e ,

Willeke F. Daamen

a , *

a

Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands;

b

Department of

Urology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands;

c

Department for Health Evidence,

Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands;

d

Radboudumc Amalia Children’s Hospital, Radboud

university medical center, Nijmegen, The Netherlands;

e

SYRCLE (SYstematic Review Centre for Laboratory Animal Experimentation), Department for Health

Evidence (section HTA), Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 5 9 4 – 6 0 6

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

Article info

Article history:

Accepted March 17, 2017

Associate Editor:

Christian Gratzke

Keywords:

Urethra

Reconstructive surgery

Tissue engineering

Systematic review

Meta-analysis

Clinical studies

Preclinical studies

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www.eu-acme.org/ europeanurology

to read and

answer questions on-line.

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then be attributed

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Abstract

Context:

Urethra repair by tissue engineering has been extensively studied in laboratory

animals and patients, but is not routinely used in clinical practice.

Objective:

To systematically investigate preclinical and clinical evidence of the efficacy

of tissue engineering for urethra repair in order to stimulate translation of preclinical

studies to the clinic.

Evidence acquisition:

A systematic search strategy was applied in PubMed and EMBASE.

Studies were independently screened for relevance by two reviewers, resulting in

80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis

to assess side effects, functionality, and study completion. Analyses for preclinical and

clinical studies were performed separately. Full circumferential and inlay procedures

were assessed independently. Evaluated parameters included seeding of cells and type

of biomaterial.

Evidence synthesis:

Meta-analysis revealed that cell seeding significantly reduced the

probability of encountering side effects in preclinical studies. Remarkably though, cells

were only sparsely used in the clinic (4/23 studies) and showed no significant reduction

of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while

in preclinical studies other biomaterials showed promising outcomes as well. No direct

comparison to current clinical practice could be made due to the limited number of

randomized controlled studies.

Conclusions:

Due to a lack of controlled (pre)clinical studies, the efficacy of tissue

engineering for urethra repair could not be determined. Meta-analysis outcome mea-

sures were similar to current treatment options described in literature. Surprisingly, it

appeared that favorable preclinical results, that is inclusion of cells, were not translated

to the clinic. Improved (pre)clinical study designs may enhance clinical translation.

Patient summary:

We reviewed all available literature on urethral tissue engineering to

assess the efficacy in preclinical and clinical studies. We show that improvements to

(pre)clinical study design is required to improve clinical translation of tissue engineering

technologies.

#

2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

y

These authors contributed equally to the study results.

* Corresponding author. Post Office Box 9101, 6500 HB Nijmegen, The Netherlands.

Tel. +31 24 36 10557; Fax: +31 24 35 40339.

E-mail address:

Willeke.Daamen@radboudumc.nl

(W.F. Daamen).

http://dx.doi.org/10.1016/j.eururo.2017.03.026

0302-2838/

#

2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.