The potential role of tissue‐engineered urethral substitution: clinical and preclinical studies

Urethral strictures and anomalies remain among the difficult problems in urology, with urethroplasty procedures being the most effective treatment options. The two major types of urethroplasty are anastomotic urethroplasty and widening the urethral lumen using flaps or grafts (i.e. substitution urethroplasty). However, no ideal material for the latter has been found so far. Designing and selecting such a material is a necessary and challenging endeavour, driving the need for further bioengineered urethral tissue research. This article reviews currently available studies on the potentialities of tissue engineering in urethral reconstruction, in particular those describing the use of both acellular and recellularized tissue‐engineered constructs in animal and human models. Possible future developments in this field are also discussed. Copyright © 2015 John Wiley & Sons, Ltd.

[1]  A. Bashir,et al.  Dorsal onlay augmentation urethroplasty with small intestinal submucosa: Modified Barbagli technique for strictures of the bulbar urethra , 2006, International journal of urology : official journal of the Japanese Urological Association.

[2]  S. Madduri,et al.  A bilayered hybrid microfibrous PLGA--acellular matrix scaffold for hollow organ tissue engineering. , 2013, Biomaterials.

[3]  S. MacNeil,et al.  Long-term follow-up after tissue-engineered buccal mucosa urethroplasty. , 2014, European urology.

[4]  R. Godwin.  Urethral stone formation following urethroplasty. , 1977, The British journal of radiology.

[5]  M. Lazzeri,et al.  One‐sided anterior urethroplasty: a new dorsal onlay graft technique , 2009, BJU international.

[6]  O. Engel,et al.  15 TISSUE - ENGINEERED BUCCAL MUCOSA URETHROPLASTY. OUTCOME OF OUR FIRST 10 PATIENTS , 2012 .

[7]  A. Mundy,et al.  The long-term results of urethroplasty. , 2003, The Journal of urology.

[8]  R. Santucci,et al.  Anastomotic urethroplasty for bulbar urethral stricture: analysis of 168 patients. , 2002, The Journal of urology.

[9]  Anthony Atala,et al.  Cell-seeded tubularized scaffolds for reconstruction of long urethral defects: a preclinical study. , 2013, European urology.

[10]  R. Santucci,et al.  Male urethral stricture disease. , 2007, The Journal of urology.

[11]  A. Atala,et al.  A novel inert collagen matrix for hypospadias repair. , 1999, The Journal of urology.

[12]  A. Atala,et al.  Acellular collagen matrix as a possible "off the shelf" biomaterial for urethral repair. , 1999, Urology.

[13]  Alexander M Seifalian,et al.  The roles of tissue engineering and vascularisation in the development of micro-vascular networks: a review. , 2005, Biomaterials.

[14]  L. Cui,et al.  Evaluation of the biocompatibility and mechanical properties of naturally derived and synthetic scaffolds for urethral reconstruction. , 2010, Journal of biomedical materials research. Part A.

[15]  A. Atala,et al.  Urethral stricture repair with an off-the-shelf collagen matrix. , 2003, The Journal of urology.

[16]  Ahmed R. Ramadan,et al.  Endoscopic urethroplasty using small intestinal submucosal patch in cases of recurrent urethral stricture: a preliminary study. , 2009, Journal of endourology.

[17]  A. Atala,et al.  Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures. , 2008, The Journal of urology.

[18]  A. Atala,et al.  Urethral replacement using cell seeded tubularized collagen matrices. , 2002, The Journal of urology.

[19]  David W. Grant,et al.  Anesthesia Duration as an Independent Risk Factor for Postoperative Complications in Free Flap Surgery: A Review of 1,305 Surgical Cases , 2013, Journal of Reconstructive Microsurgery.

[20]  S. Badylak,et al.  Rabbit urethral regeneration using small intestinal submucosa onlay grafts. , 1998, Urology.

[21]  A. Atala,et al.  SIU/ICUD Consultation on Urethral Strictures: The management of anterior urethral stricture disease using substitution urethroplasty. , 2014, Urology.

[22]  A. Morey,et al.  SIU/ICUD Consultation on Urethral Strictures: Anterior urethra--primary anastomosis. , 2014, Urology.

[23]  J. Hubbell,et al.  In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model. , 2012, Biomaterials.

[24]  A. Salonia,et al.  Long-term results of small intestinal submucosa graft in bulbar urethral reconstruction. , 2012, Urology.

[25]  James J. Yoo,et al.  Tissue-engineered autologous urethras for patients who need reconstruction: an observational study , 2011, The Lancet.

[26]  D J Mooney,et al.  Development of biocompatible synthetic extracellular matrices for tissue engineering. , 1998, Trends in biotechnology.

[27]  P. L. Le Roux.  Endoscopic urethroplasty with unseeded small intestinal submucosa collagen matrix grafts: a pilot study. , 2005, The Journal of urology.

[28]  J. Schalken,et al.  Rabbit urethra replacement with a defined biomatrix or small intestinal submucosa. , 2003, European urology.

[29]  Anthony Atala,et al.  Urine derived cells are a potential source for urological tissue reconstruction. , 2008, The Journal of urology.

[30]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[31]  A. Atala,et al.  Tubularized urethral replacement with unseeded matrices: what is the maximum distance for normal tissue regeneration? , 2008, World Journal of Urology.

[32]  A. Atala,et al.  Penile urethra replacement with autologous cell‐seeded tubularized collagen matrices , 2015, Journal of tissue engineering and regenerative medicine.

[33]  A. Stenzl,et al.  Introducing a large animal model to create urethral stricture similar to human stricture disease: a comparative experimental microscopic study. , 2012, The Journal of urology.

[34]  C. Chapple.  Anterior urethral surgery: current concepts and future directions. , 2010, European urology.

[35]  R. Skalak,et al.  Tissue engineering : a brief overview , 1991 .

[36]  Yan Hong,et al.  Peritoneal cavity as bioreactor to grow autologous tubular urethral grafts in a rabbit model , 2010, World Journal of Urology.

[37]  S. Xia,et al.  Tubularized Urethral Replacement Using Tissue-Engineered Peritoneum-Like Tissue in a Rabbit Model , 2012, Urologia Internationalis.

[38]  A. Morey,et al.  Anterior urethral strictures: etiology and characteristics. , 2005, Urology.

[39]  A. Vidlář,et al.  Porcine small intestinal submucosa graft for repair of anterior urethral strictures. , 2007, European urology.

[40]  D. Kaplan,et al.  Acellular Bi-Layer Silk Fibroin Scaffolds Support Tissue Regeneration in a Rabbit Model of Onlay Urethroplasty , 2014, PloS one.

[41]  P. Argibay,et al.  Histologic changes after urethroplasty using small intestinal submucosa unseeded with cells in rabbits with injured urethra. , 2013, Urology.

[42]  F. Montorsi,et al.  Bulbar urethroplasty using buccal mucosa grafts placed on the ventral, dorsal or lateral surface of the urethra: are results affected by the surgical technique? , 2004, The Journal of urology.

[43]  F. Fabbri,et al.  Morbidity of oral mucosa graft harvesting from a single cheek. , 2010, European urology.

[44]  Jianlin Yuan,et al.  Urethral Reconstruction with Tissue-Engineered Human Amniotic Scaffold in Rabbit Urethral Injury Models , 2014, Medical science monitor : international medical journal of experimental and clinical research.

[45]  D J Mooney,et al.  Open pore biodegradable matrices formed with gas foaming. , 1998, Journal of biomedical materials research.

[46]  A. Nordenskjöld,et al.  Prepubertal follow‐up after hypospadias repair with autologous in vitro cultured urothelial cells , 2012, Acta paediatrica.

[47]  A. Atala,et al.  Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. , 2011, Tissue engineering. Part A.

[48]  S. MacNeil,et al.  Tissue-engineered buccal mucosa urethroplasty-clinical outcomes. , 2008, European urology.

[49]  F. Cui,et al.  New ureteral scaffold constructed with composite poly(L-lactic acid)-collagen and urothelial cells by new centrifugal seeding system. , 2012, Journal of biomedical materials research. Part A.

[50]  P. Roux.  ENDOSCOPIC URETHROPLASTY WITH UNSEEDED SMALL INTESTINAL SUBMUCOSA COLLAGEN MATRIX GRAFTS: A PILOT STUDY , 2005 .

[51]  Chao Feng,et al.  Reconstruction of three-dimensional neourethra using lingual keratinocytes and corporal smooth muscle cells seeded acellular corporal spongiosum. , 2011, Tissue engineering. Part A.

[52]  Lujie Song,et al.  Tissue-engineered buccal mucosa using silk fibroin matrices for urethral reconstruction in a canine model. , 2014, The Journal of surgical research.

[53]  A. Mundy,et al.  Non‐transecting anastomotic bulbar urethroplasty: a preliminary report , 2012, BJU international.

[54]  Lujie Song,et al.  Evaluation of stretched electrospun silk fibroin matrices seeded with urothelial cells for urethra reconstruction. , 2013, The Journal of surgical research.

[55]  Anthony Atala,et al.  Regenerative medicine strategies. , 2012, Journal of pediatric surgery.

[56]  P. Eshghi,et al.  The application of tissue-engineered preputial matrix and fibrin sealant for urethral reconstruction in rabbit model , 2014, International Urology and Nephrology.

[57]  R. Kapoor,et al.  Dorsal onlay buccal mucosa versus penile skin flap urethroplasty for anterior urethral strictures: results from a randomized prospective trial. , 2006, The Journal of urology.

[58]  E. Palminteri,et al.  Small intestinal submucosa (SIS) graft urethroplasty: short-term results. , 2007, European urology.

[59]  Hongbin Li,et al.  Urethral reconstruction with tissue engineering and RNA interference techniques in rabbits. , 2013, Urology.

[60]  Y. Na,et al.  [Homologous dermal acellular matrix graft for urethral reconstruction in man (report of 16 cases)]. , 2005, Zhonghua yi xue za zhi.

[61]  M. Lazzeri,et al.  Ventral onlay oral mucosal graft bulbar urethroplasty , 2011, BJU international.

[62]  Masayuki Yamato,et al.  Two-layer tissue engineered urethra using oral epithelial and muscle derived cells. , 2012, The Journal of urology.

[63]  R. Langer,et al.  Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture. , 1994, Biomaterials.

[64]  Robert Langer,et al.  Biodegradable Polymer Scaffolds for Tissue Engineering , 1994, Bio/Technology.

[65]  C. Chapple,et al.  Tissue engineering in urethral reconstruction--an update. , 2013, Asian journal of andrology.

[66]  R. Dahiya,et al.  Homologous acellular matrix graft for urethral reconstruction in the rabbit: histological and functional evaluation. , 2000, The Journal of urology.

[67]  P. Gouma,et al.  Electrospun bioscaffolds that mimic the topology of extracellular matrix. , 2006, Nanomedicine : nanotechnology, biology, and medicine.

[68]  A. Atala.  Tissue engineering of reproductive tissues and organs. , 2012, Fertility and sterility.

[69]  L. Cui,et al.  Urethral reconstruction using oral keratinocyte seeded bladder acellular matrix grafts. , 2008, The Journal of urology.

[70]  Anthony Atala,et al.  Urethral Stricture Repair With an Off-the-shelf Collagen Matrix , 2003 .

[71]  S. Soker,et al.  The use of thermal treatments to enhance the mechanical properties of electrospun poly(ɛ-caprolactone) scaffolds , 2008 .

[72]  S. Hauser,et al.  Small intestine submucosa in urethral stricture repair in a consecutive series. , 2006, Urology.

[73]  C. Chapple,et al.  A systematic review of graft augmentation urethroplasty techniques for the treatment of anterior urethral strictures. , 2011, European urology.

[74]  S. Brandes,et al.  Advanced Male Urethral and Genital Reconstructive Surgery , 2014 .

[75]  Jia Lishan.  Repairing urethral defect with adipose-derived mesenchymal stem cells seeded on a porous silk fibroin scaffold in rabbits , 2010 .

[76]  J. Hubbell,et al.  High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells. , 2011, Biomaterials.

[77]  Long-term study of male rabbit urethral mucosa reconstruction using epidermal cell. , 2008, Asian journal of andrology.

[78]  D. Varisco,et al.  Reconstructive Urethroplasty Using Porcine Acellular Matrix (SIS): Evolution of the Grafting Technique and Results of 10-Year Experience , 2011, Urologia.

[79]  C. Fred Fox,et al.  Tissue engineering : proceedings of a workshop held at Granlibakken, Lake Tahoe, California, February 26-29, 1988 , 1988 .

[80]  A. Atala,et al.  Implantation of autologous urine derived stem cells expressing vascular endothelial growth factor for potential use in genitourinary reconstruction. , 2011, The Journal of urology.

[81]  Y. Ikada,et al.  Fabrication of an Optimal Urethral Graft Using Collagen-Sponge Tubes Reinforced with Copoly(L-Lactide/ε-Caprolactone) Fabric , 2007 .

[82]  A. Atala.  Tissue engineering for the replacement of organ function in the genitourinary system , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[83]  F. Silver,et al.  Cell growth on collagen: a review of tissue engineering using scaffolds containing extracellular matrix. , 1992, Journal of long-term effects of medical implants.

[84]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[85]  M. Lazzeri,et al.  Current controversies in reconstructive surgery of the anterior urethra: a clinical overview. , 2012, International braz j urol : official journal of the Brazilian Society of Urology.

[86]  M. Rizzo,et al.  Long-term results of anterior and posterior urethroplasty with actuarial evaluation of the success rates. , 1997, The Journal of urology.