title: Engineered acellular collagen scaffold for endogenous cell guidance, a novel approach in urethral regeneration.
abstract: The treatment of congenital malformations or injuries of the urethra using existing autologous tissues can be associated with post-operative complications. Using rat-tail collagen, we have engineered an acellular high-density collagen tube. These tubes were made of 2 layers and they could sustain greater burst pressures than the monolayered tubes. Although it remains a weak material this 2 layered tube could be sutured to the native urethra. In 20 male New Zealand white rabbits, 2cm long grafts were sutured in place after subtotal excision of the urethra. This long-term study was performed in Lausanne (Switzerland) and in Kuala Lumpur (Malaysia). No catheter was placed post-operatively. All rabbits survived the surgical implantation. The animals were evaluated at 1, 3, 6, and 9months by contrast voiding cysto-urethrography, histological examination and immunohistochemistry. Spontaneous re-population of urothelial and smooth muscle cells on all grafts was demonstrated. Cellular organization increased with time, however, 20% of both fistula and stenosis could be observed post-operatively. This off-the shelf scaffold with a promising urethral regeneration has a potential for clinical application.
  
  
  
  In this study we have tissue engineered a novel cell free tubular collagen based scaffold and used it as a urethral graft in a rabbit model. The novelty of our technique is that the tube can be sutured. Testing showed better burst pressures and the grafts could then be successfully implanted after a urethral excision. This long term study demonstrated excellent biocompatibility of the 2cm graft and gradual regeneration with time, challenging the current literature. Finally, the main impact is that we describe an off-the-shelf and cost-effective product with comparable surgical outcome to the cellular grafts.
authors.affiliation: Department of Pediatric Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Kalitha
authors.initials: K
authors.lastname: Pinnagoda
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Hans M
authors.initials: HM
authors.lastname: Larsson
authors.affiliation: Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia; Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Vythilingam
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Elif
authors.initials: E
authors.lastname: Vardar
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Engelhardt
authors.affiliation: Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rajendrarao C
authors.initials: RC
authors.lastname: Thambidorai
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute for Molecular Engineering, University of Chicago, Chicago, IL, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.affiliation: Laboratory for Regenerative Medicine and Pharmacobiology, Institute for Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Electronic address: peter.frey@epfl.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Frey
mesh_terms: D000818:Animals; D003094:Collagen / Q000494:pharmacology*; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008297:Male; D008422:Materials Testing; D011817:Rabbits; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D023822:Tissue Engineering / Q000379:methods*; D014521:Urethra / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000601:surgery
chemical_list: D003094:Collagen
keywords: Acellular; Collagen; Rabbit; Tissue engineered; Tubular; Urethral graft