title: Tubularized urethral replacement with unseeded matrices: what is the maximum distance for normal tissue regeneration?
abstract: OBJECTIVE
  Complete urethral replacement using unseeded matrices has been proposed as a possible therapy in cases of congenital or acquired anomalies producing significant defects. Tissue regeneration involves fibrin deposition, re-epithelialization, and remodeling that are limited by the size of the defect. Scar formation occurs because of an inability of native cells to regenerate over the defect before fibrosis takes place. We investigated the maximum potential distance of normal native tissue regeneration over a range of distances using acellular matrices for tubular grafts as an experimental model.
  
  
  METHODS
  Tubularized urethroplasties were performed in 12 male rabbits using acellular matrices of bladder submucosa at varying lengths (0.5, 1, 2, and 3 cm). Serial urethrography was performed at 1, 3, and 4 weeks. Animals were sacrificed at 1, 3, and 4 weeks and the grafts harvested. Urothelial and smooth muscle cell regeneration was documented histologically with H&E and Masson's trichrome stains.
  
  
  RESULTS
  Urethrograms demonstrated normal urethral calibers in the 0.5 cm group at all time points. The evolution of a stricture was demonstrated in the 1, 2, and 3 cm grafts by 4 weeks. Histologically all grafts demonstrated ingrowth of urothelial cells from the anastomotic sites at 1 week. By 4 weeks, the 0.5 cm grafts had a normal transitional layer of epithelium surrounded by a layer of muscle within the wall of the urethral lumen. The 1, 2, and 3 cm grafts showed ingrowth and normal cellular regeneration only at the anastomotic edges with increased collagen deposition and fibrosis toward the center by 2 weeks, and dense fibrin deposition throughout the grafts by 4 weeks.
  
  
  CONCLUSIONS
  The maximum defect distance suitable for normal tissue formation using acellular grafts that rely on the native cells for tissue regeneration appears to be 0.5 cm. The indications for the use of acellular matrices in tubularized grafts may therefore be limited by the size of the defect to be repaired.
authors.affiliation: Department of Urology, LAC+USC Medical Center, 1200 N. State St. Suite 5900, Los Angeles, CA 90033, USA. rdorin@usc.edu
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Dorin
authors.forename: Hans G
authors.initials: HG
authors.lastname: Pohl
authors.forename: Roger E
authors.initials: RE
authors.lastname: De Filippo
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology*; D005355:Fibrosis; D008297:Male; D023421:Models, Animal; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D014517:Ureteral Obstruction / Q000473:pathology / Q000517:prevention & control; D014521:Urethra / Q000166:cytology* / Q000502:physiology* / Q000601:surgery; D013520:Urologic Surgical Procedures