EURURO Vol. 72 No. 4

Platinum Priority – Editorial

Referring to the article published on pp. 594–606 of this issue

Tissue Engineering of the Urethra: Solid Basic Research and

Farsighted Planning are Required for Clinical Application

Karl-Dietrich Sievert

[1_TD$DIFF]

, b , *

[2_TD$DIFF]

Department of Urology, University of Rostock Medical

[3_TD$DIFF]

Center, Rostock, Germany;

Department of Urology, University Hospital of Vienna, Vienna, Germany

Defects of the urethra include a wide range of conditions,

from congenital birth defects such as hypospadias to

urethral strictures due to iatrogenic injury, infection, or

trauma. Various surgical reconstructive techniques have

been developed to restore functionality

[1]

. However, open

questions remain as to which reconstruction procedures

can best ensure urine flow and ejaculatory function

[1,2]

Both partial and full circumferential reconstruction of the

urethral tube require the use of tissue. Buccal mucosa

currently represents the closest replacement material for

transitional epitheliumof the urethrawithout the risk of side

effects such as hair growth, which may occur when dermal

skin is used. However, harvesting of buccal tissue from the

mouth requires a second surgical procedure, which might

cause further side effects

[3]

. Although tissue engineering

(TE) of urothelium has not focused on reconstruction of the

spongious corpora, its use would provide an opportunity to

premanufacture the tissue required for reconstruction and

would eliminate the risk of comorbidities due to a second

surgical procedure (buccal cavity/mouth).

Versteegden and colleagues

[4]

performed a compre-

hensive meta-analysis of preclinical and clinical studies

investigating urethral TE. The first part of the meta-analysis

examined evidence from preclinical studies and found that

outcomes were better with seeded than with non-seeded TE

matrices. Because most animal models studies were

performed in ‘‘healthy’’ animals, it remains an open

question whether the cell healing that occurred was

dependent on ‘‘virgin’’ tissue, which also most likely

supported healing and cell ingrowth.

In the second part of the meta-analysis, Versteegden et al

[4]

investigated the clinical environment. The published

clinical studies did not provide evidence to confirm

preclinical findings regarding the benefits of preseeded

matrices. However, most of these studies used a decel-

lularized matrix, and only three of the 13 clinical studies

eligible for the meta-analysis investigated seeded matrices.

Furthermore, 75% of the patients had undergone one or

more previous treatment procedures.

Ultimately, the aim of TE reconstruction is not only to

improve postoperative functional outcome using materials

such as off-the-shelf or customized materials with autolo-

gous cells supporting the regenerative aspect of the healing

process, but also to avoid or minimize the need for

additional surgery

[5] .

One of the very few studies that

achieved this outcome was by el-Kassaby et al

[6]

, who

reported that patients who underwent urethral reconstruc-

tion with TE material (decellularized bladder matrix

without any additional cell seeding) as the initial surgery

had a better outcome than those with previous surgeries.

Most of the clinical studies included in the meta-analysis

used small intestine submucosa (SIS) for reconstructive

surgery. This biomaterial was approved by the US Food and

Drug Administration (FDA) in 2004 for use in implantation to

reinforce soft tissue where weakness exists or reinforcement

is needed

[7] .

However, only a small number of published

studies have investigated this material. The original

preclinical investigations had inconsistent outcomes, pri-

marily because of differences in the procedures used in SIS

preparation. Furthermore, the thickness of the material

varies from one to four layers, probably causing further

differences. Moreover, the commercially available SIS

requires additional treatments to the tissue (eg, radiation)

to fulfill FDA requirements, besides other specifications

[8] .

Experimental materials have been used in only very

limited numbers of clinical studies and patients. Thus, a

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

ava ilable at

www.sciencedirect.com

journal homepage:

www.eu ropeanurology.com

DOI of original article:

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

* Department of Urology, University of Rostock Medical

[3_TD$DIFF]

Center, Rostock, Germany.

E-mail address:

kd_sievert@hotmail.com

http://dx.doi.org/10.1016/j.eururo.2017.04.025

0302-2838/