Biomedical Engineering Reference
In-Depth Information
11. Seeking novel targets in the pursuit of rational stent design.
Given the fact that the urinary conditioning film has been directly implicated in causing
both bacterial adhesion and associated/non-associated encrustation, it becomes important
to switch our focus from designing a biomaterial that inhibits direct bacterial and
ion/mineral deposition to one that inhibits conditioning film components. It is important to
focus on understanding this biological target further and the first step is to identify
components of the conditioning film. Santin et al have previously identified human serum
albumin as well as Tamm-Horsfall Protein (THP) as major conditioning film components
found on four stents removed from patients (Santin, Motta et al. 1999). More recently,
Canales et al have studied the conditioning films of stents removed from 27 patients,
identifying hemoglobin alpha and beta chain, albumin, calgranulin B, fibrinogen beta chain,
vitronectin, annexin A1, calgranulin A, fibrinogen gamma chain, and THP as the ten most
common adherent components (Canales, Higgins et al. 2009). In addition, this group also
hypothesized that the presence of histones likely contribute to stent encrustation given their
unique net positive charge. Despite the fact that these papers have contributed to a large
extent to the identification of conditioning film components, it still needs to be determined
whether urinary conditioning films differ between stent types or patients, as the molecules
targeted in stent design should be “universal” and need to be common between patients and
stent types.
Our group has recently compared the composition of conditioning films found on certain
stents from Boston Scientific (Polaris) to those on Bard stents (Inlay) after they have been
removed from patients (Lange et al, unpublished data). Both of these stents differ in their
biomaterials, as the Polaris stent is made of an olefinic copolymer, while the InLay stent is
made of polyurethane. To date, there does not appear to be a significant difference in the
conditioning film composition from patients with the same stent type or between the two
different stent types, indicating that conditioning film deposition is not affected by different
stent biomaterials or patients. Similar results have also been obtained by Tieszer et al, who
showed via X-ray photoelectron spectroscopy that the elemental composition of
conditioning film components was unaffected by stent biomaterial or patient characteristics
(Tieszer, Reid et al. 1998). Our study found that the fifteen most common proteins include
cytokeratins, serum albumin, hemoglobin subunits alpha and beta, THP, fibrinogen gamma
chain, protein S100A9, vitronectin and apolipoprotein. Interestingly, the majority of the
fifteen most commonly found proteins are binding sites for bacteria and thus facilitate
bacterial adhesion and biofilm formation. In addition to this, the presence of calcium
binding proteins such as the S100 proteins or THP may act as a nidus for encrustation. We
found that significantly less Polaris stents contained THP and fibrinogen gamma chain
compared to the InLay stent, eliminating these two proteins as potential targets. Overall
these results validate specific conditioning film components as targets for future stent
biomaterial design as they appear to play a role in stent associated infection and
encrustation. Further analysis will have to be performed to determine whether
commonalities exist between the physical characteristics of these components and whether
they can be targeted to inhibit their deposition.
Our current experiments are aimed at studying the temporal deposition of urinary
components onto the surface of stent pieces, as some proteins such as serum albumin are
known to bind to other proteins rather than the surfaces themselves. In the context of
urinary component deposition, it is possible that certain proteins with a higher affinity to
