| Autor: |
Roelofs LA; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Oosterwijk E; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Kortmann BB; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Daamen WF; 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands ., Tiemessen DM; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Brouwer KM; 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands ., Eggink AJ; 3 Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center , Rotterdam, The Netherlands ., Crevels AJ; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Wijnen RM; 4 Pediatric Surgery, Erasmus MC, University Medical Center , Rotterdam, The Netherlands ., van Kuppevelt TH; 2 Department of Biochemistry Radboud University Medical Center , Nijmegen, The Netherlands ., Geutjes PJ; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands ., Feitz WF; 1 Department of Urology Radboudumc Amalia Children's Hospital, Radboud University Medical Center , Nijmegen, The Netherlands . |
| Abstrakt: |
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. |
