Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction

Abstract

BACKGROUND: Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODS: Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS: Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION: Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a prevascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.

Fabrication of Adipose-Derived Stem Cell-Based Self-Assembled Scaffold under Hypoxia and Mechanical Stimulation for Urethral Tissue Engineering

“…Although, skin grafts are readily used in genitourinary reconstructive surgery, their application can nevertheless lead to complications such as infection due to hair growth, and stone formation in the neourethra. Moreover, there are limitations in utilizing the non-hairy skin of patients with lichen sclerosis, as it can lead to graft failure in the long-term, due to fibrosis [ 2 , 3 , 4 , 5 , 6 ].…”

“…Among strategies in tissue engineering of urethra reviewed elsewhere [ 6 ], constructing of urethral tissue using self-assembly approach happens to be promising. Self-assembled scaffold production as a replacement to human connective tissue was first introduced by Dr. Francois A. Auger’s team and it is based on production and deposition of extracellular matrix (ECM) by dermal fibroblasts (DFs) [ 14 ] or adipose-derived stem cells (ASCs) [ 15 ] under the influence of ascorbic acid.…”

Non-Muscular Invasive Bladder Cancer: Re-envisioning Therapeutic Journey from Traditional to Regenerative Interventions

“…The presence of urothelial cells induces BMSCs to differentiate into urothelial-like cells [129]. The scaffold with better structural supports and porosity and hypoxia preconditioning also improves bladder regenerative potential of BMSCs [135]. In addition, seeding BMSCs on to the scaffold also exert an additive effect on its bladder regenerating potential post-TURBT.…”

Electrospinning: Application and Prospects for Urologic Tissue Engineering

“…Nevertheless, the use of autologous grafts is associated with several complications such as limited donor sites and tissues, the need for additional harvest, and the probability for donor site morbidity ( Pederzoli et al, 2019 ). Tissue engineering as an alternative approach, holds the potential of addressing these limitations using autologous cells and biodegradable scaffolds ( Figure 2F ; Simsek et al, 2018a ; Rashidbenam et al, 2019 ). An ideal scaffold for urethral tissue engineering should be biocompatible, biodegradable, and own suitable three dimentional microstructure and biomechanical attributes to promote the proliferation of seeded cells and ingrowth of native tissues when was implanted.…”

“…An ideal scaffold for urethral tissue engineering should be biocompatible, biodegradable, and own suitable three dimentional microstructure and biomechanical attributes to promote the proliferation of seeded cells and ingrowth of native tissues when was implanted. The scaffold should have enough strength to tolerate the mechanical forces exerted during the surgery and at the same time, should have a matched mechanical compliance to the native urethra to stretch and recoil during penile erection and dilate the lumen during micturition ( Selim et al, 2011 ; de Kemp et al, 2015 ; Zhang et al, 2015 ; Simsek et al, 2018b ; Rashidbenam et al, 2019 ). In addition, the scaffold should also act as an impermeable barrier to preserve the underlying tissues from the toxic components of urine ( de Kemp et al, 2015 ).…”