Biomaterials in Urology - Beyond Drug Eluting and Degradable - A Rational Approach to Ureteral Stent Design

Abstract

Ureteral stents are commonly used in urology to provide urinary drainage of the upper tracts, particularly following treatment of urolithiasis. Stents are commonly plagued with infections and encrustation, particularly in stone-forming patients (Denstedt and Cadieux 2009). This involves a multistep process outlined in Figure 1. The first step is formation of a conditioning film comprised of urinary proteins, ions, and crystals that are deposited at the stent surface (Tieszer, Reid et al. 1998). The conditioning film becomes an attractive surface for bacteria to adhere to and forms a biofilm which can lead to a urinary tract infection or encrustation (Wollin, Tieszer et al. 1998; Choong and Whitfield 2000; Choong, Wood et al. 2001; Shaw, Choong et al. 2005). Bacteria have been demonstrated to adhere to the stent surface in up to 90% of indwelling stents, which in 27% of cases leads to a positive urine culture (Reid, Denstedt et al. 1992). Ideally, ureteral stent biomaterials would be able to limit or completely prevent the processes shown in Figure 1. Various attempts have been made to reduce the deposition of crystals, bacteria, and protein on stent surfaces including using low surface energy biomaterials (Tieszer, Reid et al. 1998), heparin coating (Cauda, Cauda et al. 2008), antimicrobial eluting biomaterials (Cadieux, Chew et al. 2006; Chew, Cadieux et al. 2006; Wignall, Goneau et al. 2008; Cadieux, Chew et al. 2009), diamond-like carbon coatings (Laube, Kleinen et al. 2007), polyethylene glycol and marine mussel adhesive proteins (Pechey, Elwood et al. 2009) to name just a few. Most have limited effectiveness and some have even shown increased bacterial adhesion compared to controls in the case of heparin coating (Lange, Elwood et al. 2009). While drug-eluting technology of biomaterials is both readily available and used clinically in other fields, its role in urology has been limited. Triclosan was used recently in ureteral stents. It held promise in in vitro (Chew, Cadieux et al. 2006) and animal infection models (Cadieux, Chew et al. 2006) but it fared poorly in those patients requiring chronic ureteral stents (Cadieux, Chew et al. 2009). The current methodology of technological implementation surrounding ureteral stent coating and design have come from trial and error or are borrowed technologies from coronary and vascular stenting. The time has come for the urological world to apply the same types of scientific discovery and development to problems specific to urinary devices rather than just applying the end product from other areas of medicine. What works in vascular stenting may not be directly applicable to the urinary environment.