Use of indwelling catheters and stents long-term in the urinary tract is often limited due to the occurrence of encrustation and biofilm formation To date, there are no biomaterials used in the urinary tract that are completely biocompatible and capable of withstanding the effects of the urinary environment for extended time periods In the absence of urinary infection, calcium-oxalate is the principal component of the encrusted material Since oxalate concentrations of urine are the more important parameter for calcium-oxalate saturation and metastable urinary supersaturation, reduction of oxalate in the urinary environment in which stents and catheters are placed should reduce or even prevent encrustation This hypothesis is supported by our Phase I feasibility studies in which we were able to define conditions for coating """"""""functionalized"""""""" silicone elastomer, a commonly used biomaterial for urological devices, with the oxalate-degrading enzyme, oxalate decarboxylase In vitro studies demonstrated that silicone discs covalently linked with oxalate decarboxylase were resistant to calcium-oxalate encrustation and bacterial adhesion, in contrast to uncoated silicone discs, when placed in artificial urine In this Phase II grant proposal, we propose to continue development of the enzyme-coating techniques to enhance further the stability and functionality of the immobilized enzyme This coating technology will then be used to develop a prototype enzyme-coated stent to be tested for its ability to prevent encrustation and bacterial adhesion in an in vivo pig model Thus, by the end of this Phase II grant, we will have completed the pre-clinical testing of a prototype encrustation-resistant stent At that time, measures will be taken to bring this enzyme-coating technology to the commercial level by licensing it to stent and catheter manufacturers for final product development under FDA regulated design control, scale-up production, and clinical testing.
