**7. Stent coatings**

One of the most common stent coatings is hydrogel, which consists of hydrophilic polymers that absorb water and increase lubricity and elasticity.(Marmieri, Pettenati et al. 1996; John, Rajpurkar et al. 2007) These properties facilitate stent placement, making the device rigid and easily maneuverable in its dry state, but once exposed to urine, the hydrogel begins to absorb and trap water in its polyanionic structure, causing it to soften and theoretically increase patient comfort. Data on encrustation and infection are less convincing, as hydrogel has been shown to both reduce (Gorman, Tunney et al. 1998) and increase encrustation and biofilm formation (Desgrandchamps, Moulinier et al. 1997). Hydrogels have been used in an attempt to soak and retain antibiotics but an *in vitro* study did not show increased efficacy of bacterial killing compared to non-antibiotic soaked hydrogel coated stents (John, Rajpurkar et al. 2007).

Glycosaminoglycan (GAG), a normal constituent of urine, is a natural inhibitor of crystallization. Other novel stent coatings include pentosan polysulfate (Zupkas, Parsons et al. 2000) (a member of the Glycosaminoglycan family a normal constituent of urine and a natural inhibitor of crystallization), phosphorylcholine (Stickler, Evans et al. 2002) (a constituent of human erythrocytes that mimics a natural lipid membrane), and polyvinyl pyrrolidone (Tunney and Gorman 2002) (a hydrophilic coating, similar to hydrogel, that absorbs water).

Attempts to reduce encrustation have included other stent coatings, such as the bacterial enzyme, oxalate decarboxylase, which has been shown to decrease encrustation in silicone discs placed in rabbit bladders.(Watterson, Cadieux et al. 2003) A novel coating of mPEG-DOPA3, a natural constituent produced by mussels that produces strong adhesive properties, also has the ability to avoid biofouling in the environment. The polyethyelene (PEG) component provides the antifouling property while the DOPA3 provides the adherence that PEG lacks on its own. Adherence of these combined compounds on silicone disks has resulted in a strong ability to resist bacterial adherence and growth in vitro.(Ko 2007) Further development of this type of coating was studied *in vivo* using a rabbit *E. coli* cystitis model (Pechey, Elwood et al. 2009). This study showed that the anti-adhesive coating was successful at inhibiting bacterial adhesion and decreased the incidence of infection, however it was unable to prevent non-bacterial mediated encrustation.

Plasma deposited diamond like carbon coatings have been used to coat stents in an attempt to prevent encrustation (Laube, Kleinen et al. 2007). *In vitro* experiments have shown a 30% decrease in encrustation of these stents in artificial urine compared to the non-coated controls. Ongoing clinical trials appear to indicate a further enhancement of these results *in vivo*, however a mechanism for this needs to be elucidated. Encrustation of ureteral stents remains one of the most common problems associated with ureteral stenting and more research will need to be done for an optimal stent design which resists the deposition of bacteria, minerals and proteins.

In vascular medicine, the anticoagulant heparin has been shown to inhibit bacterial attachment to venuous catheters (Ruggieri, Hanno et al. 1987; Appelgren, Ransjo et al. 1996), which has been attributed to its highly negative charge. Similarly, effects of heparin have

also been observed for ureteral stents. Riedl *et al*. (Riedl, Witkowski et al. 2002) used heaprin-coated and uncoated polyurethane ureteral stents and inserted them into obstructed ureters with indwelling times between 2 and 6 weeks. Electron microscopy showed that the uncoated control stents were covered with amorphous anorganic deposits and bacterial biofilms as early as 2 weeks following stent insertion, while the heparin-coated stents remeined unaffected by encrustation following 6 weeks of indwelling time. Cauda *et al*. (Cauda, Cauda et al. 2008) performed a long term study involving patients with bilateral ureteral obstructions treated via the insertion of a heparin-coated stent into one ureter, and an uncoated control stent into the other ureter. Overall, the uncoated control stents were found to be encrusted with amorphous, crystalline inorganic deposits and bacterial biofilm as early as 1 month post-insertion, while the heparin-coated stents remained visibly free of encrustation as long as 10 months post-insertion. Biofilm encrustation was evident only on the external surface of the coated stent after 1 year of being in place. Heparin coated ureteral stents (Radiance Stent, Cook Urological) were tested in an *in vitro* model of infected urine and did not display any reduction in bacterial adherence compared to control stents (Lange, Elwood et al. 2009). These preliminary results are somewhat promising, but clinical trials involving a larger number of patients are needed to ensure that heparin coating of stents is effective across a broader patient range.
