Collagen-Based Biomatrix with Growth Factors for Postnatal Repair in a Sheep Model with Bladder Exstrophy

Abstract

Purpose Bladder exstrophy comes with extensive reconstructive surgery. Replacement of the currently used techniques by biomatrices might improve the final functional outcome. In this study we used a growth factor enriched collagen-based biomatrix to enhance bladder regeneration in a sheep model with bladder exstrophy. Material and Methods Biomatrices were prepared and crosslinked to increase structural integrity and to incorporate heparin. Heparin was used to specifically bind heparin binding growth factors (VEGF, FGF-2 and EGF) to induce bioactivity. In 12 fetal sheep a bladder exstrophy was prepared at 79 days' gestation. Lambs were born at 140 days' gestation with normal delivery. Bladder defect was reconstructed with plain collagen biomatrix (group 1) or a growth factor enriched biomatrix (group 2). Lambs were evaluated 1 or 6 months after surgery with contrast cystogram, urodynamic assessment and histology. Results After birth all bladder defects (n = 12) were open and reconstruction was performed. One lamb died during delivery. For all groups the cystogramic images were close to normal. After 6 months, the engineered bladders were more compliant and had greater capacity than those closed with the plain collagen biomatrix. Histological evaluation revealed increased angiogenesis and urothelial cell growth in the growth factor loaded biomatrix. Overall, improved maturation of bladder tissue was seen in time. Conclusions Coverage of bladder defects with a VEGF and FGF-2 loaded collagen biomatrix resulted in less wound contraction, increased angiogenesis and urothelial lining. The growth factor enriched biomatrix can be useful in repair and regeneration of bladder and cloacal exstrophies to improve neonatal outcome.