Biomedical Engineering Reference
In-Depth Information
These components are believed to facilitate bacterial adhesion leading to bacterial
colonization, proliferation, and biofilm formation with subsequent infection. Once a biofilm
has formed, this environment facilitates recurrent infection and eradication of bacteria is
difficult. Bacteria embedded within the biofilm change to a low metabolic state and undergo
a low replication rate, thus rendering antibiotics (which are most effective against bacteria in
high metabolic states and undergoing replication) ineffective. In many cases, embedded
bacteria are also protected since antibiotics cannot penetrate the biofilm and the protecting
exopolysaccharide layer excreted by the bacteria onto its surface. Thirdly, bacteria can
upregulate resistance genes once inside the biofilm (Lewis 2005).
Aside from biofilm formation and infection, another symptom associated with patient
morbidity caused by indwelling ureteral stents is device encrustation. Stent encrustation can
be idiopathic and caused by calcium oxalate crystals. In other instances, stent encrustation
can be attributed to the presence of urease producing bacteria, which break down urinary
ammonia into ammonium (thus effectively taking a hydrogen ion), which results in a rise in
urinary pH and crystallization of magnesium, ammonium and phosphate ions. These
crystals then adhere to the surface of the stent via the interaction with components of the
conditioning film. The conditioning film on the stent surface is considered to be a great
contributor to bacterial associated encrustation because it facilitates bacterial adhesion and
crystal adhesion to the stent surface. In addition to this, the conditioning film has also been
implicated in idiopathic encrustation (in the absence of bacteria) of the stent with calcium
oxalate crystals. As such, certain conditioning film components have been proposed to be
able to bind minerals from the urine, forming a nidus for crystal growth and device
encrustation. To date, we have identified 3 potential targets to interrupt the sequence of
events involved in the evolution of stent encrustation and infection: 1) preventing
conditioning film formation, 2) preventing initial adherence and encrustation and 3)
inhibition of further bacterial proliferation.
10. Current stent biomaterial design
Over the years, attempts have been made at preventing stent associated symptoms by
targeting either bacterial adhesion and encrustation or inhibition of bacterial proliferation.
Drug eluting technology to prevent bacterial adhesion has previously been used in a
triclosan-eluting ureteral stent. Triclosan is an antimicrobial found in over 800 commercially
available products such as soaps, hand scrubs, and toothpaste. This stent proved to be
successful at eliminating bacterial loads
in vitro
(Chew, Cadieux et al. 2006)
as well as a
Proteus mirabilis
urinary tract infection in a rabbit model (Cadieux, Chew et al. 2006), but did
not show any significant differences in long term clinical trials (Cadieux, Chew et al. 2009).
Similarly a heparin- coated stent was designed to prevent bacterial adhesion given the
material's highly negative charge. This stent was shown to decrease encrustation in patients
(Hildebrandt, Sayyad et al. 2001; Riedl, Witkowski et al. 2002; Cauda, Cauda et al. 2008),
however was unable to prevent bacterial adhesion (Lange, Elwood et al. 2009). The use of
diamond-like amorphous carbon as a coating on stents is a new technology that has shown
some promise in terms of inhibiting encrustation (Laube, Bradenahl et al. 2006; Laube,
Kleinen et al. 2007), however experiments aimed at determining its ability to inhibit bacterial
adhesion is lacking. One of the drawbacks of these new technologies is the fact that they are
susceptible to blockage by the deposition of the urinary conditioning film, which covers any
coating and blocks elution of drugs from the stent, rendering it ineffective and promoting
bacterial adhesion and encrustation via mechanisms discussed above.
