Unfolding the truth about bladder function

According to Anne Robertson, the bladder is not considered a particularly glamorous organ, despite hosting many of the same physiological elements and processes as the heart.

Luckily for the fields of urology and biomechanics, that hasn’t stopped Robertson and her team from trying to understand it — a commitment that’s led to a collaboration between the University of Pittsburgh and University of Sheffield to develop the first digital twin of the bladder — and a new publication revealing that bladders don’t fill up like a simple balloon as previously thought, but instead have large inner folds that expand and retract to accommodate changes in volume and pressure.

“The bladder remains one of the most underexplored organs in the biomechanics community,” said mechanical engineering and materials science (MEMS) PhD candidate Fatemeh Azari, “and this publication decisively bridges a gap in knowledge that has persisted for over three decades.”

Led by Azari and Robertson, distinguished service professor of mechanical engineering and materials science (MEMS) at the Swanson School of Engineering, the team’s findings, “Elucidating the high compliance mechanism by which the urinary bladder fills under low pressures,” were published in the July 2025 edition of Scientific Reports.

The group’s main objective was to uncover how the bladder fills with urine at low pressure by examining both its structure and function. While previous studies proposed that small folds (rugae) in the bladder wall allow it to expand, the team found that much larger folds, about ten times bigger than once thought, are the key to its flexibility. Using high-resolution micro-CT and multiphoton imaging, the team analyzed how the bladder wall changed shape as it filled in a rat model.

“When we looked at the bladder’s geometry, we realized it was so much more complex than what had been previously thought.” Azari said. “The bladder wall thickness isn’t uniform, and what used to look like empty spaces on earlier CT scans were actually full of collagen and elastin structures that we could finally see by using multiphoton imaging.”

A complementary experiment then linked these changes to pressure–volume behavior during filling, using a customized imaging-inflation system to visualize the mechanisms behind how bladders fill. The team discovered that the large-scale folds that formed during voiding drove over 95% of the urine out of the bladder. These folds then flattened during filling, enabling the bladder to fill with very little increase in pressure — a critical component for protecting the kidneys and avoiding leakage.

“We observed that bladder filling occurs in two distinct phases, rather than behaving like a simple expanding balloon.” Azari said. “The first phase involves a large increase in volume with minimal pressure change, followed by a high-pressure phase where pressure rises sharply as the bladder continues to fill.”

The team’s study marks the first full-organ mechanical test to capture how a healthy bladder fills, providing critical insight into urological conditions like bladder outlet obstruction (BOO). A common disorder in aging men, the flow of urine from the bladder into the urethra is blocked, causing the bladder to enlarge, thicken, and lose efficiency. Looking ahead, Robertson hopes to continually adapt this model to understand better treatment methods for conditions like BOO and bladder cancer.

“A common treatment for BOO is to surgically reduce the obstruction by removing part of the prostrate with the goal of regaining healthy function.” Robertson said. “Even this invasive treatment fails in about one third of the cases. We're creating a digital twin model for the BOO bladder so that we can determine which patient factors affect outcome and identify more effective personalized treatment strategies.”

This work was supported by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01 AG056944 and R01 DK133434. Along with Azari and Robertson, authors include Simon Watkins, Yasutaka Tobe, Lori A. Birder, Naoki Yoshimura and Kanako Matsuoka at the University of Pittsburgh, Christopher Hardin, University of Missouri School of Medicine, and Paul N. Watton, University of Sheffield, UK.