Prosthetic stents and in-dwelling catheters are frequently used in urological and nephrological medicine for the management of urinary and peritoneal dialysis flow, haemodialysis, and drainage of renal calculi following laser or lithotripsy treatment. Unfortunately, the use of long-term indwelling urinary catheters and stents in the urinary tract suffers from encrustation and bacterial adhesion that increases the risk for blockage of the device as well as urinary tract infections. Important in these events is the ability of microorganisms to attach to the biomaterial and form biofilms, a process dependent on the deposition of urinary components (especially calcium oxalate, calcium apatite and struvite) onto the biomaterial. Epidemiological studies have indicated urolithiasis as the major risk factor for stent encrustation, apparently due to the supersaturation of urolithiasis patients' urine with lithogenic components. As oxalate concentration of urine is the most important parameter for calcium oxalate saturation and metastable urinary supersaturation, reduction of oxalate from the urinary environment in which stents and catheters are placed should prevent or reduce encrustation. The long-term goal of this grant application is to develop an encrustation-resistant coating for urological devices. In the current Phase I SBIR grant application, we propose to evaluate the three known oxalate-degrading enzyme systems for a) efficacy in coating silicon- latex biomaterial surfaces, b) stability of enzymatic activity following coating plus its survival in a urinary environment, c) ability to reduce oxalate levels in a urinary environment, and d) prevention of calcium oxalate encrustation and bacterial deposition. Data from these experiments will verify the feasibility of this approach to develop an encrustation-resistant coating for urological stents. An encrustation- resistant coating, together with advances in new biomaterials, would benefit an increasingly large patient population.
Encrustation is a serious complication of the use of urinary catheters and urethral stents that can lead to renal impairment in the absence of endourological intervention. Coating biomaterial surfaces of the urinary devices with oxalate degrading enzymes alone or in conjunction with bactericidal coatings will be a major breakthrough in the urinary device industry. Such devices could benefit urological patients, a population where >10% of hospitalizations require catheterization and stenting.