Thromboresistance of Silicones Modified with PEO-Silane Amphiphiles.

The antifouling properties of poly(ethylene oxide) (PEO)-silane amphiphiles as surface-modifying additives (SMAs) in a condensation cure silicone have been previously demonstrated against simple protein solutions. Comprising an oligo(dimethylsiloxane) tether (m = 13 or 30) and PEO segment (n = 8), sustained protein resistance was achieved even in the absence of a cross-linkable triethoxysilane group, particularly when comprising the longer tether. To probe their potential for thromboresistance, PEO-silane amphiphile SMAs were used to bulk-modify silicones and evaluated for adhesion resistance against whole human blood under both static and dynamic conditions. Both a cross-linkable (XL diblock, m = 13) and a non-cross-linkable (Diblock, m = 30) SMA were evaluated at various concentrations (5-50 µmol SMA/g silicone) in a condensation cure silicone. Under static conditions, silicones modified with either SMA at concentrations of 10 µmol/g or greater were effective in reducing adhesion of human fibrinogen and platelets. Dynamic testing further showed that modified silicones were able to reduce protein adsorption and thrombus formation. This occurred at 5 and 10 µmol/g for silicones modified with XL diblock, m = 13 and Diblock, m = 30 SMAs, respectively. Combined, these results indicate the effectiveness of PEO-silane amphiphiles as SMAs in silicone for improved thromboresistance.

Thrombosis-on-a-chip: Prospective impact of microphysiological models of vascular thrombosis.

The most common pathology of the blood-vessel organ system is thrombosis or undesirable clotting of the blood. Thrombosis is life threatening as more than 25% of such cases lead to sudden death from stroke and myocardial infarction. Even though the process of thrombosis has been extensively investigated with animal models, its exact pathobiology in different blood vessels is not yet fully understood and drug assessment remains unpredictable. This is primarily because the cause for thrombus formation is multifactorial and depends on the interplay of flow patterns within the blood vessel, the vessel wall or endothelium, extracellular matrix, parenchymal tissue, and the cellular and plasma components of the blood. Current in vitro and animal models do not mimic or dissect this organ-level complexity faithfully. However, microfluidic technology has recently been deployed to effectively recapitulate blood-endothelial-epithelial interactions in the onset of thrombosis in blood vessels. This technology is promising because it permits inclusion of primary human cells and blood obtained from patients, which is currently lacking in other in vitro models of thrombosis. In this review, we summarize the current state-of-the-art and practices in microfluidics and expected improvements in this field that will impact basic understanding of thrombosis, drug discovery and personalized medicine.