Design Optimization of Perfluorinated Liquid‐Infused Surfaces for Blood‐Contacting Applications

Abstract

Tethered‐liquid perfluorocarbon (TLP) coatings show promise for blood‐contacting medical device applications to reduce blood adhesion and delay thrombosis. However, their fabrication and longevity under external fluid flow is not well characterized. A vapor phase silanization reaction leading to the formation of tethered‐perfluorocarbon (TP) layers containing large bumpy aggregates, 300 ± 200 nm thick, on top of an underlying 35 ± 15 nm thick uniform coating is reported. The vapor phase method compares favorably to the well‐established liquid phase deposition to reproducibly create slippery coatings on silicon and polystyrene with very low water sliding angles (2° ± 1°), without the need to control humidity conditions. The TP layer retains perfluorinated lubricants up to 20 000 s–1, using a cone‐and‐plate rheometer, with the higher viscosity lubricant perfluoroperhydrophenanthrene being more resistant to depletion than perfluorodecalin. TLP infused with either of the lubricants effectively reduces adhesion of fibrin from human whole blood relative to TP and control hydrophilic and hydrophobic surfaces. The combination of highly fluorinated TP coatings grafted from the vapor phase to create nanoscale structured surfaces infused with higher viscosity lubricant may be the most suitable combination for clinical applications of liquid‐infused surfaces to reduce thrombosis in blood‐contacting medical devices under flow.

Mechanisms for Reduced Fibrin Clot Formation on Liquid‐Infused Surfaces

“…[1,6,30,32] Liquid-infused surfaces (LIS) are made of a polymer network or microstructure infused with a highly repellent liquid lubricant layer, [33] and in recent years, have emerged as excellent candidates to reduce material thrombosis. [34][35][36][37] Tethered-liquid perfluorocarbons (TLP) are a type of LIS, consisting of a layer of tethered-perfluorocarbons (TP) covalently bound to an oxidized surface which is subsequently infused with a bioinert liquidperfluorocarbon (LP) lubricant. [35,36] The chemistry and structure of the fluorinated TP layers is designed to immobilize the fluorinated liquid lubricant, via favorable van der Waals interactions and, on molecular-structured or nanostructured surfaces, by capillary adhesion.…”

“…[33] The infused surfaces are water repellent and anti-adhesive to most liquids and solids, as characterized by a value of sliding angle of water droplets around 2°. [37] These low sliding angle values are retained as long as the lubricant is present, and retention of the lubricant occurs only on treated (perfluorinated) substrates. On untreated hydrophilic substrates, the lubricant tends to dewet under an aqueous phase, so the anti-adhesive properties are lost.…”

“…On untreated hydrophilic substrates, the lubricant tends to dewet under an aqueous phase, so the anti-adhesive properties are lost. [34,37] Numerous studies have shown that TLP coatings effectively reduced protein adhesion and thrombus formation, in vitro, compared to untreated materials. [34,38] Pronounced reductions in platelet adhesion, activation, and adhesion of polymerized fibrin from human whole blood were found on TLP compared to TP and untreated controls.…”

“…[34,38] Pronounced reductions in platelet adhesion, activation, and adhesion of polymerized fibrin from human whole blood were found on TLP compared to TP and untreated controls. [34,[37][38][39] Additionally, promising results from in vivo studies under blood flow suggested the ability of TLP to reduce thrombosis using animal models (for 6 and 8 h). [34,40] However, extended 72-h studies of TLP-coated extracorporeal systems were unable to prevent occlusion due to thrombosis.…”

Robust and durable liquid-repellent surfaces

“…Recently, Hong et al investigated the optimization of perfluorinated SLISs for blood-contacting applications. 540 The authors prepared tethered-perfluorocarbon layers containing large bumpy aggregates (300 AE 200 nm thick) on top of an underlying uniform coating (35 AE 15 nm thick) by a vapor phase silanization reaction, which were then infused with perfluoroperhydrophenanthrene or perfluorodecalin to create SLISs. Although the two lubricants were similar in preventing fibrin adhesion from human whole blood, the higher viscosity of perfluoroperhydrophenanthrene than perfluorodecalin (28.2 mPa s vs. 5.1 mPa s) made it the preferred lubricant for reducing thrombosis in medical applications under blood flow condition due to its greater resistance towards shear-flow induced depletion.…”