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An engineered micropattern to reduce bacterial colonization, platelet adhesion and fibrin sheath formation for improved biocompatibility of central venous catheters.

May RM, Magin CM, Mann EE, Drinker MC, Fraser JC, Siedlecki CA, Brennan AB, Reddy ST - Clin Transl Med (2015)

Bottom Line: Antimicrobial and antithrombotic drugs can prevent infections and thrombosis-related complications, but have associated resistance and safety risks.Blood and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S. epidermidis colonization by 70% (p ≤ 0.05) and 71% (p < 0.01), respectively, when compared to preconditioned unpatterned controls.These results suggest that the incorporation of the Sharklet micropattern on the surface of a CVC may inhibit the initial events that lead to CRBSI and CRT.

View Article: PubMed Central - PubMed

Affiliation: Sharklet Technologies, Inc, 12635 E. Montview Blvd. Suite 155, Aurora, CO 80045, CO USA.

ABSTRACT

Background: Catheter-related bloodstream infections (CRBSIs) and catheter-related thrombosis (CRT) are common complications of central venous catheters (CVC), which are used to monitor patient health and deliver medications. CVCs are subject to protein adsorption and platelet adhesion as well as colonization by the natural skin flora (i.e. Staphylococcus aureus and Staphylococcus epidermidis). Antimicrobial and antithrombotic drugs can prevent infections and thrombosis-related complications, but have associated resistance and safety risks. Surface topographies have shown promise in limiting platelet and bacterial adhesion, so it was hypothesized that an engineered Sharklet micropattern, inspired by shark-skin, may provide a combined approach as it has wide reaching anti-fouling capabilities. To assess the feasibility for this micropattern to improve CVC-related healthcare outcomes, bacterial colonization and platelet interactions were analyzed in vitro on a material common for vascular access devices.

Methods: To evaluate bacterial inhibition after simulated vascular exposure, micropatterned thermoplastic polyurethane surfaces were preconditioned with blood proteins in vitro then subjected to a bacterial challenge for 1 and 18 h. Platelet adhesion was assessed with fluorescent microscopy after incubation of the surfaces with platelet-rich plasma (PRP) supplemented with calcium. Platelet activation was further assessed by monitoring fibrin formation with fluorescent microscopy after exposure of the surfaces to platelet-rich plasma (PRP) supplemented with calcium in a flow-cell. Results are reported as percent reductions and significance is based on t-tests and ANOVA models of log reductions. All experiments were replicated at least three times.

Results: Blood and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S. epidermidis colonization by 70% (p ≤ 0.05) and 71% (p < 0.01), respectively, when compared to preconditioned unpatterned controls. Additionally, platelet adhesion and fibrin sheath formation were reduced by 86% and 80% (p < 0.05), respectively, on the micropattern, when compared to controls.

Conclusions: The Sharklet micropattern, in a CVC-relevant thermoplastic polyurethane, significantly reduced bacterial colonization and relevant platelet interactions after simulated vascular exposure. These results suggest that the incorporation of the Sharklet micropattern on the surface of a CVC may inhibit the initial events that lead to CRBSI and CRT.

No MeSH data available.


Related in: MedlinePlus

The Sharklet micropattern reduces fibrin sheath formation resulting from platelet activation. Representative images of immunostained fibrinogen on (a) unpatterned, (b) +3SK2x2 and (c) -3SK2x2 TPU surfaces. Quantification of fluorescent images revealed that both Sharklet micropatterns significantly reduce fibrinogen area coverage compared to unpatterned controls. Scale bar, 50 μm.
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Fig4: The Sharklet micropattern reduces fibrin sheath formation resulting from platelet activation. Representative images of immunostained fibrinogen on (a) unpatterned, (b) +3SK2x2 and (c) -3SK2x2 TPU surfaces. Quantification of fluorescent images revealed that both Sharklet micropatterns significantly reduce fibrinogen area coverage compared to unpatterned controls. Scale bar, 50 μm.

Mentions: An ideal blood contacting biomaterial would reduce both platelet adhesion and activation to inhibit thrombotic activity. To determine whether the Sharklet micropattern would influence platelet activation in addition to attachment, fibrin sheath formation was measured as a clinically relevant end-point. The-3SK2×2 and +3SK2×2 micropatterns in TPU were evaluated and compared to unpatterned TPU controls. Results show 70% and 80% reductions (p < 0.05) in fibrinogen coverage, respectively (Figure 4). The representative images highlight the differences in fibrin strand formation and coverage on the unpatterned TPU surface compared to the distribution of globular fibrinogen on the micropatterned surfaces (Figure 4). The +3SK2×2 micropattern showed significantly lower fibrin sheath coverage than the-3SK2×2 micropattern across experiments (Tukey test p = 0.05, Figure 4d).Figure 4


An engineered micropattern to reduce bacterial colonization, platelet adhesion and fibrin sheath formation for improved biocompatibility of central venous catheters.

May RM, Magin CM, Mann EE, Drinker MC, Fraser JC, Siedlecki CA, Brennan AB, Reddy ST - Clin Transl Med (2015)

The Sharklet micropattern reduces fibrin sheath formation resulting from platelet activation. Representative images of immunostained fibrinogen on (a) unpatterned, (b) +3SK2x2 and (c) -3SK2x2 TPU surfaces. Quantification of fluorescent images revealed that both Sharklet micropatterns significantly reduce fibrinogen area coverage compared to unpatterned controls. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385044&req=5

Fig4: The Sharklet micropattern reduces fibrin sheath formation resulting from platelet activation. Representative images of immunostained fibrinogen on (a) unpatterned, (b) +3SK2x2 and (c) -3SK2x2 TPU surfaces. Quantification of fluorescent images revealed that both Sharklet micropatterns significantly reduce fibrinogen area coverage compared to unpatterned controls. Scale bar, 50 μm.
Mentions: An ideal blood contacting biomaterial would reduce both platelet adhesion and activation to inhibit thrombotic activity. To determine whether the Sharklet micropattern would influence platelet activation in addition to attachment, fibrin sheath formation was measured as a clinically relevant end-point. The-3SK2×2 and +3SK2×2 micropatterns in TPU were evaluated and compared to unpatterned TPU controls. Results show 70% and 80% reductions (p < 0.05) in fibrinogen coverage, respectively (Figure 4). The representative images highlight the differences in fibrin strand formation and coverage on the unpatterned TPU surface compared to the distribution of globular fibrinogen on the micropatterned surfaces (Figure 4). The +3SK2×2 micropattern showed significantly lower fibrin sheath coverage than the-3SK2×2 micropattern across experiments (Tukey test p = 0.05, Figure 4d).Figure 4

Bottom Line: Antimicrobial and antithrombotic drugs can prevent infections and thrombosis-related complications, but have associated resistance and safety risks.Blood and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S. epidermidis colonization by 70% (p ≤ 0.05) and 71% (p < 0.01), respectively, when compared to preconditioned unpatterned controls.These results suggest that the incorporation of the Sharklet micropattern on the surface of a CVC may inhibit the initial events that lead to CRBSI and CRT.

View Article: PubMed Central - PubMed

Affiliation: Sharklet Technologies, Inc, 12635 E. Montview Blvd. Suite 155, Aurora, CO 80045, CO USA.

ABSTRACT

Background: Catheter-related bloodstream infections (CRBSIs) and catheter-related thrombosis (CRT) are common complications of central venous catheters (CVC), which are used to monitor patient health and deliver medications. CVCs are subject to protein adsorption and platelet adhesion as well as colonization by the natural skin flora (i.e. Staphylococcus aureus and Staphylococcus epidermidis). Antimicrobial and antithrombotic drugs can prevent infections and thrombosis-related complications, but have associated resistance and safety risks. Surface topographies have shown promise in limiting platelet and bacterial adhesion, so it was hypothesized that an engineered Sharklet micropattern, inspired by shark-skin, may provide a combined approach as it has wide reaching anti-fouling capabilities. To assess the feasibility for this micropattern to improve CVC-related healthcare outcomes, bacterial colonization and platelet interactions were analyzed in vitro on a material common for vascular access devices.

Methods: To evaluate bacterial inhibition after simulated vascular exposure, micropatterned thermoplastic polyurethane surfaces were preconditioned with blood proteins in vitro then subjected to a bacterial challenge for 1 and 18 h. Platelet adhesion was assessed with fluorescent microscopy after incubation of the surfaces with platelet-rich plasma (PRP) supplemented with calcium. Platelet activation was further assessed by monitoring fibrin formation with fluorescent microscopy after exposure of the surfaces to platelet-rich plasma (PRP) supplemented with calcium in a flow-cell. Results are reported as percent reductions and significance is based on t-tests and ANOVA models of log reductions. All experiments were replicated at least three times.

Results: Blood and serum conditioned micropatterned surfaces reduced 18 h S. aureus and S. epidermidis colonization by 70% (p ≤ 0.05) and 71% (p < 0.01), respectively, when compared to preconditioned unpatterned controls. Additionally, platelet adhesion and fibrin sheath formation were reduced by 86% and 80% (p < 0.05), respectively, on the micropattern, when compared to controls.

Conclusions: The Sharklet micropattern, in a CVC-relevant thermoplastic polyurethane, significantly reduced bacterial colonization and relevant platelet interactions after simulated vascular exposure. These results suggest that the incorporation of the Sharklet micropattern on the surface of a CVC may inhibit the initial events that lead to CRBSI and CRT.

No MeSH data available.


Related in: MedlinePlus