Tissue engineering and biomaterials research

There are a number of conditions, including cancer, where the ability of the bladder to store useful volumes of urine at kidney-sparing low pressures is compromised. Our studies of normal urothelium have led us to investigate the potential of using cells propagated in the laboratory to reconstruct or replace bladders damaged by disease or dysfunction.

In current surgical practice, the bladder may be reconstructed using a vascularised, detubularised segment of bowel. However, the bowel epithelium is unsuited to long term exposure to urine and the procedure, termed enterocystoplasty, results in serious long term clinical side effects, including an increased risk of cancer.

Two of the main areas being focused on at the JBU, which have now entered clinical translation include:

Composite Cystoplasty. Aiming to engineering a kidney sparing continent urine-storing neobladder. The plan is to combine urothelial cells with vascularised host smooth muscle tissue grafts to be able to augment or reconstruct bladders of patients with end stage bladder disease.
Biomaterials. This approach aims to reconstruct the bladder by incorporating a natural or synthetic biomaterial. This is the most attractive long term solution as it would open the way to developing an off-the-shelf product. However, this goal is some way off as no suitable biomaterial has yet been developed and most acellular biomaterials result in a fibrotic reaction when incorporated into the bladder. The need is for a biomaterial that contains relevant growth and cell signalling cues which, when implanted as an acellular scaffold, harnesses a tissue regenerative/developmental response in vivo. This requires a better understanding of the molecular basis of the urothelial wound response and urothelial:stromal cell interactions during development and tissue repair if these are to be exploited in the generation of "smart" biomaterials. We are investigating natural and synthetic biomaterials as potential scaffolds for bladder reconstruction and tissue engineering and have developed a porcine acellular bladder matrix (PABM) (WO/2007/110634). We are also examining synthetic scaffolds based on PLGA and PCL polymers and strategies for functionalisation by growth factors. PABM allows the creation of a scaffold which can be incorporated into a partially dissected bladder wall to build capacity.

Glossary

Neobladder - replacement bladder created from a section of your bowel and attached to your urethra, which means you can pass urine in the same way as with a normal bladder.