title: Bladder Regeneration Using a Smart Acellular Collagen Scaffold with Growth Factors VEGF, FGF2 and HB-EGF.
abstract: Tissue engineering may become an alternative to current bladder augmentation techniques. Large scaffolds are needed for clinically significant augmentation, but can result in fibrosis and graft shrinkage. The purpose of this study was to investigate whether smart acellular collagen-heparin scaffolds with growth factors (GFs) VEGF, FGF2, and HB-EGF enhance bladder tissue regeneration and bladder capacity in a large animal model of diseased bladder. Scaffolds of bovine type I collagen with heparin and VEGF, FGF2, and HB-EGF measuring 3.2 cm in diameter were prepared. In 23 fetal sheep, a bladder exstrophy was surgically created at 79 days of gestation. One week after birth (at full term), the bladder was reconstructed by primary closure (PC group) or using a collagen-heparin scaffold with GFs (COLGF group) and compared to a historical group reconstructed with a collagen scaffold without GFs (COL group). Functional (video urodynamics) and histological evaluation was performed 1 and 6 months after bladder repair. The overall survival rate was 57%. Cystograms were normal in all animals, except for low-grade reflux in all groups. Urodynamics showed no statistically significant differences in bladder capacity and compliance between groups. Histological evaluation at 1 month revealed increased urothelium formation, improved angiogenesis, and enhanced ingrowth of smooth muscle cells (SMCs) in the COLGF group compared to the COL group. At 6 months, improved SMC ingrowth was found in the COLGF group compared to the COL group; both scaffold groups showed normal urothelial lining and standard extracellular matrix development. Bladder regeneration using a collagen-heparin scaffold with VEGF, FGF2, and HB-EGF improved bladder tissue regeneration in a large animal model of diseased bladder. Larger GF-loaded constructs need to be tested to reach clinically significant augmentation.
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Luc A J
authors.initials: LA
authors.lastname: Roelofs
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Barbara B M
authors.initials: BB
authors.lastname: Kortmann
authors.affiliation: 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Tiemessen
authors.affiliation: 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Katrien M
authors.initials: KM
authors.lastname: Brouwer
authors.affiliation: 3 Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center , Rotterdam, The Netherlands .
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Eggink
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: A Jane
authors.initials: AJ
authors.lastname: Crevels
authors.affiliation: 4 Pediatric Surgery, Erasmus MC, University Medical Center , Rotterdam, The Netherlands .
authors.forename: Rene M H
authors.initials: RM
authors.lastname: Wijnen
authors.affiliation: 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Geutjes
authors.affiliation: 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Wout F J
authors.initials: WF
authors.lastname: Feitz
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor / Q000737:chemistry / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*; D012756:Sheep; D054457:Tissue Scaffolds / Q000737:chemistry*; D001743:Urinary Bladder / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology
chemical_list: D066257:Heparin-binding EGF-like Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D003094:Collagen