Augmentation enterocystoplasty has remained the gold standard for bladder augmentation for over a century, yet it continues to carry well-known metabolic and surgical morbidity from incorporating bowel into the urinary tract. Prior efforts using both non-biologic and biologic acellular matrices have demonstrated only small volume bladder regeneration in the order of one square centimeter and requires specialized preparation. We asked a simple question, could a readily available, inert, off the shelf titanium scaffold drive full thickness bladder regeneration at a clinically meaningful scale? To investigate this, three Yucatan pigs underwent open implantation of a four centimeter equilateral triangle of 99.9% purity, 0.03 millimeter thick titanium foil, which was secured to the bladder wall using an Endo GIA stapler through a five centimeter infraumbilical incision.
Each animal was followed for a period of one year with follow-ups being conducted at 0, 3, 6, 12, 20, 26, 40, and 52 weeks. Each follow-up period involved testing bladder capacity at 40 centimeters of water intra physical pressure using an optical pressure sensor, flexible cystoscopy, a cystogram, renal ultrasound, and serum biochemistry. At one year, the animals were euthanized for cystectomy and histopathology. Our findings demonstrated that by six months, all three animals had expelled the titanium augmented to the bladder lumen and the cystoscopic images shown here demonstrate progressive tissue coverage at the prior implantation site. Bladder capacity increased significantly in two of the three animals with Pig B demonstrating a roughly nine milliliter per week increase and Pig C demonstrating 3.7 milliliter per week increases in bladder capacity both with strong R-squared values.
Critically, serum creatinine remains stable across the entire cohort and renal ultrasound showed no hydronephrosis bilaterally at one year and at all follow-ups. There were no urinary leaks noted at any point during our follow-up period. Histopathology demonstrated full thickness bladder regeneration with organized urothelium, lamina propria and detrusor smooth muscle at the augmentation site, which was indistinguishable in architecture from native controlled tissue.
In summary, a stable titanium foil scaffold produced full thickness bladder regeneration with a statistically significant increase in bladder capacity and without ultrasonographic or biochemical evidence of upper tract deterioration. This represents a potentially transformative bowel-free approach to bladder augmentation and we look forward to advancing this work towards larger animal and clinical studies. Thank you.