DISCOVERY IN BLADDER CANCER
Hope for the Future: An Engineered Bladder
“We envision developing a clinically functional, tissue-engineered bladder by the end of 2025,” says Trinity Bivalacqua, M.D., Ph.D., Director of Urologic Oncology. He and the Brady’s Regenerative Urology research team are working hard toward this goal, buoyed by recent breakthroughs in the practical mechanics of how to do it.
A collagen scaffold provides an elegant framework for the patient’s own cells to grow into a new bladder.
The key is a scaffold that allows the patient’s own cells to grow over it. Bivalacqua, is the first investigator to successfully complete a Phase 1 clinical trial in bladder cancer patients using this “autologous cell-seeded scaffold” to replace the urinary system after radical cystectomy. “Although the Phase 1 trial demonstrated regeneration of urinary tissue, the neo- urinary conduit was not durable,” so the team brainstormed and “outlined a road to success,” Bivalacqua says.
The interdisciplinary team includes Bivalacqua, a surgeon-scientist, Anirudha Singh, Ph.D., a biomaterials and tissue engineer, and Nikolai Sopko M.D., Ph.D., a stem cell biologist. Their strategy begins with designing more durable materials “that will function as urinary tissue for a long time. The use of regenerated urinary tissue is necessary.” Currently, replacement bladders are made using part of the patient’s own intestine; this is not ideal and complications are common. Singh’s laboratory recently developed a novel process to make collagen scaffolds for “urological neo-organs.” Collagen, Bivalacqua explains, “is one of the most suitable biomaterials, and is a natural choice here.” But developing a good scaffold proved a tough challenge, “until Singh’s laboratory created a simple yet elegant collagen molding technology,which resembles synthetic polymer processing methods, to create neo-organs.”
The versatile design has “unprecedented features and user-controlled mechanical and biological properties.” A patent is pending. “Specifically, this process developed hollow and tubular collagen systems ranging from ureter-like micro-sized tubings to tubes with designer lumen that resembles intestinal villi, to complex seaweed-like structures as multiple mini-bladders for regenerative urology applications.”
This research is supported by the Greenberg Bladder Cancer Institute Foundation and the research findings will be published in Nature Biomedical Engineering. As Singh continues to refine the scaffolds, Bivalacqua and Sopko’s laboratories are developing animal models for testing them.