**1. Introduction**

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.

Biomaterials in Urology - Beyond Drug Eluting

**3. Current stent biomaterials** 

patient discomfort.

**4. New materials** 

**5. Metal ureteral stents** 

and Degradable - A Rational Approach to Ureteral Stent Design 461

removal involves multiple surgical procedures (Rana and Sabooh 2007) and may result in

The synthetic polymer, polyethylene, was previously used in stent construction, but was abandoned due to its stiffness, brittleness, and tendency to fragment. Blends of polyethylene and other polymers, such as polyurethane, have been shown to resist encrustation (Gorman, Tunney et al. 1998; Gomha, Sheir et al. 2004). Silicone is currently the most biocompatible stent material as it is the most resistant to biofilm formation, infection and encrustation (Watterson, Cadieux et al. 2003), and is one of the most lubricious materials available (Jones, Garvin et al. 2004); however, its softness and elasticity make it difficult to handle, particularly through tortuous or tight ureters. In addition, the low tensile strength of silicone makes it susceptible to extrinsic compression. The development of new stent materials aimed to meld the flexible and elastic properties of silicone with the rigidity of polyethylene which resulted in the development of polyurethane, the most common class of polymer currently used in stents. Polyurethane, however, is a stiff material that causes patient discomfort and significant ureteral ulceration and erosion have been reported in an animal model (Marx, Bettmann et al. 1988). New proprietary materials and combinations are softer, more comfortable, and easier to maneuver within the urinary tract. Examples of commonly used materials in stents include Percuflex® (Boston Scientific Corporation, Natick, MA), Silitek® (Surgitek, Medical Engineering Corporation, Racine, WI, USA), C-Flex® (Consolidated Polymer Technologies, Clearwater, FL, USA), Tecoflex® (Thermedics, Wilmington, MA, USA), and ethylene-vinyl-acetate (from the polyefin family of which polyethylene is a member). They have been designed to provide rigidity to facilitate handling by the surgeon and to provide adequate drainage while being soft enough to limit

New materials include metal stents that are designed to keep the ureter open despite extrinsic ureteral compression secondary to lymphadenopathy due to malignancy. Ureteric obstruction may result in decreased renal function, pain, or infection requiring urinary diversion (Chitale, Scott-Barrett et al. 2002; Allen, Longhorn et al. 2010). As these stents must remain in place for long periods of time, they require frequent exchanges because they are susceptible to infection and encrustation with increased indwelling time. The goal in this patient population is to develop a stent that maintains ureteral patency during extrinsic compression, is soft to minimize discomfort, and is resistant to encrustation and infection.

Metal ureteral stents were introduced by Pauer in 1992 (Pauer and Lugmayr 1992) and have been utilized in the treatment of malignant ureteric obstruction (Kulkarni and Bellamy 2001; Liatsikos, Karnabatidis et al. 2009; Masood, Papatsoris et al. 2010; Papatsoris and Buchholz 2010; Sountoulides, Kaplan et al. 2010), ureteral strictures (Daskalopoulos, Hatzidakis et al. 2001; Papatsoris and Buchholz 2010), and ureteropelvic junction obstruction (Barbalias, Liatsikos et al. 2002; Masood, Papatsoris et al. 2010; Benson, Taylor et al. 2011). Current

loss of the renal unit or potentially even death (Singh, Srinivastava et al. 2005).

Fig. 1. The processes following stent insertion that lead to bacterial adhesion, infection, and encrustation. Following stent insertion, urinary components deposit on the surface, forming anchor points for both bacteria as well as ions/minerals. Subsequent bacterial colonization and proliferation leads to the formation of a resistant biofilm that leads to subsequent infection. In addition the interaction of ions/minerals with conditioning film components and bacterial induced crystallization will facilitate encrustation of the device. Inhibition of the common step of conditioning film deposition is a potential step in preventing patient symptoms associated with indwelling ureteral stents.
