Autologous urothelial cells were seeded on the acellular dermis in order to treat scrotal or perineal hypospadias and pronounced chordee 
. The study involved six patients, urethroscopy and biopsy of the neourethras were performed at 3–4 and 6–8 years postoperatively. All patients could void without straining and urethroscopy showed a well-formed and wide penile urethra without sacculation or diverticula.
The same material was used in five patients who underwent urethroplasty 
. Excision of entire graft due to scarring was necessary in one patient, partial excision in one patient, and there was stricture recurrence in three patients.
was applied in two studies. One study described using standard techniques such as ventral onlay, dorsal onlay, dorsal inlay and combined with MukoCell®
in 38 patients. This study reported 32 patients (84.2%) as success and 6 patients (15.8%) as failure due to the need to undergo further urethral reconstruction 
. The second study was a multicenter, prospective, monitored non-interventional observational trial 
which included 99 patients with recurrent urethral strictures. To manufacture the graft, biopsy of oral mucosa was harvested and submucosa was separated and used to establish primary culture of the epithelial cells. Success rates ranged between 85.7% and 0% depending on high or low surgical experience.
While many preclinical studies have been performed, TE is still not used as an alternative treatment in routine clinical practice, except for a select patient group with a history of failed repairs 
Potential advantages of regenerative techniques are now overlooked by several reasons. In summary, these reasons are: (i) quality of clinical studies, (ii) cost and complexity of TE constructs, (iii) regulatory issues and legislation aspects.
For common use of TE in clinical practice, large RCTs must prove superiority or at least non inferiority over conventional treatment. RCT allows valid inferences considering cause and effect of clinical interventions 
. Without proper RCTs, no direct comparisons with current clinical practice (buccal urethroplasty) can be made. A recent systematic review of urethral TE showed that complex two-stage urethroplasty has complication-free rates and functionality of approximately 62%, 67%, and 36% 
, which is similar to the outcome of TE urethras. This suggests that urethral TE may be a valid alternative for further investigation 
One of the important drawbacks of TE for investigation and development is that the trial of a TE construct is not simply a test of a new medicinal product. The development of TE constructs includes trials of a complete process in vitro, in vivo or ex-vivo (construction, extensive testing for cytotoxicity, biodegradability, biomechanics, implantation, follow-up, regenerative effect of the TE product in the patient, analysis, and the final functional outcome) 
. Moreover, standardization of a surgical intervention is difficult; new TE products may have unique properties for the surgeon who conducts an implantation of the TE product. The surgical technique may be refined and changed over time due to the surgical learning curve. Consequently, in multicenter studies, the differences in skills and experiences of the operating teams may introduce further variation, provided there is not a robust number of patients 
. This can be clearly seen in a multicenter study 
, where the outcome of the implanted TE constructs clearly depended on surgical experience.
The major disadvantage of the TE approach is the high cost of production and lack of off-the-shelf availability products. These limitations can be (and must be) overcome by continuous scientific developments with industry involvement. As was mentioned before, high-quality phase 1 and 2 studies are needed with long-term follow up, which should be followed by careful commercialization. Hand in hand, it is necessary to create multidisciplinary high-volume centers with appropriate experience in TE that follow GMP protocols. Establishing dedicated working groups of clinical and biotechnology experts should be the cornerstone of the transition of TE products into clinical practice. The clinical and research teams must work closely to coordinate the timing of cell harvesting, cell-seeding, TE construct maturation (bioreactors) and eventual urethroplasty. These interdisciplinary teams will be able to conduct trials (preclinical and clinical) in an effective way, based on simultaneous, continuous cooperation. This process is time consuming and expensive, but the cost-effectiveness of TE will ultimately improve after broader adoption of this technique. It is necessary to involve industry and financing to facilitate large-scale production of scaffolds and biomaterials based on standardized protocols. Determining the cost-effectiveness of TE products may be very complex because it is not easy to determine what to include in the calculation of costs of treatment. TE construction contains biologically active molecules and/or cells and its behavior in the body is less predictable than that of a medical device with “stable” and predictable properties 
When considering cost-effectiveness in urology, it is important to illustrate involvement of industry and urologic surgeons into robotic surgery. Even though robotic surgery is clearly not cost effective with comparable surgical outcomes (in comparison to open and laparoscopic surgery), it is widely popular and robotic centers are growing in numbers 
Another reason for slow adoption of TE products into clinical practice can be the extensive culture time required for TE constructs. On the other hand, reconstructive urethral surgeries are usually performed on an elective basis, so this should not be a crucial problem.
Regenerative medicine and TE involve cell therapies, gene therapy and biomedical engineering techniques. That is why a TE product is difficult to define due to the extent and complexity it encompasses. These products are now regulated in specific legislations 
Any medicinal product that can be used in the EU market requires registration, assessment and approval by the Committee for Advanced Therapies at the European Medicines Agency. The process requires substantial financial, laboratory and human resources, and such products must undergo meticulous regulatory evaluation such as safety testing and confirmation of GMP before approval and widespread use 
. By definition, a TE product is categorized as “an advanced therapy medicinal product (ATMP) that contains or consists of engineered cells or tissues and is presented as having properties for, or is used in or administered to human beings with a view to regenerating, repairing or replacing a human tissue” 
. Consequently, TE products must undergo strict and complex assessment before entering markets to be widely and commonly used in clinical practice. This can also influence scientists and clinicians considering development and testing of TE urethral replacements, especially when appropriate material such as buccal mucosa or skin is readily available.
Urethral TE has made slow progress in clinical practice so far. The TE approach is promising and effective in the management of urethral strictures, but in simple cases and short strictures where local tissues or buccal mucosa are available, this should remain the gold standard. Though significant progress to achieving a safe and reliable TE construct has been made, many issues remain that need to be addressed: better design of trials, namely RCTs, better cooperation of research groups and centralization of AMTEP that could lead to reduction of costs and slowly proceed to commercialization of “off the shelf” products. The development and subsequent approval of a TE product require further significant financial and human resources. So far, research of TE of the urethra has not yet been translated into a clinically available material. In the future, 3D bioprinting could help streamline the creation of seeded tubular urethral constructs with the added benefit of patient-tailored designs, increasing the efficiency of generation of these TE urethras for clinical applications.