Plasma‐deposited tetraglyme surfaces greatly reduce total blood protein adsorption, contact activation, platelet adhesion, platelet procoagulant activity, and in vitro thrombus deposition

Abstract

The ability of tetraethylene glycol dimethyl ether (tetraglyme) plasma deposited coatings exhibiting ultralow fibrinogen adsorption to reduce blood activation was studied with six in vitro methods, namely fibrinogen and von Willebrand's factor adsorption, total protein adsorption, clotting time in recalcified plasma, platelet adhesion and procoagulant activity, and whole blood thrombosis in a disturbed flow catheter model. Surface plasmon resonance results showed that tetraglyme surfaces strongly resisted the adsorption of all proteins from human plasma. The clotting time in the presence of tetraglyme surfaces was lengthened compared with controls, indicating a lower activation of the intrinsic coagulation cascade. Platelet adhesion and thrombin generation by adherent platelets were greatly reduced on tetraglyme-coated materials, compared with uncoated and Biospan-coated glass slides. In the in vitro disturbed blood flow model, tetraglyme plasma coated catheters had 50% less thrombus than did the uncoated catheters. Tetraglyme-coated materials thus had greatly reduced blood interactions as measured with all six methods. The improved blood compatibility of plasma-deposited tetraglyme is thus not only due to their reduced platelet adhesion and activation, but also to a generalized reduction in blood interactions.

Quantifying the Performance of Protein‐Resisting Surfaces at Ultra‐Low Protein Coverages using Kinesin Motor Proteins as Probes

“…3). Precoating (EG) 3 OH-terminated SAM surfaces with casein followed by exposure to 17.5 nM of kinesin for 5 min reduced the observed microtubule landing rate from ∼31 mm -2 s -1 to ∼2 mm -2 s -1 , corresponding to a 15-fold reduction in kinesin surface density (data not shown).…”

“…As a result, the performance of highly non-fouling surfaces can be determined and optimized. For example, the adsorption of kinesin to PEGMA surfaces is twenty-fold reduced compared to (EG) 3 OH-terminated SAM surfaces. We hope that the low technical requirements (fluorescence microscope with camera) and the commercial availability of a kinesin motility kit (Cytoskeleton Inc.) make this method widely accessible.…”

“…With the principle of the kinesin/microtubule based assay established, we shifted our focus to two types of highly non-fouling surfaces, (EG) 3 OH-terminated SAMs and polyethylene Figure 1. Sketch of principle: Adsorption of kinesin motor proteins to a non-fouling surface can be quantified by measuring initial microtubule landing rates.…”

“…Initial efforts to create adsorption-resistant surfaces succeeded in reducing the adsorption by 80% compared to untreated surfaces to 100 ng cm -2 by employing poly(ethylene glycol) coatings.[1]Recently, optimization of brush density and morphology has reduced adsorption to 1 ng cm -2 or less.[2] These coverages, equal to about one tenth of a percent of a monolayer, represent the detection limit for several characterization techniques, including SPR [2,3] and radiolabeling.[4] However, biological effects can be observed for protein coverages below this detection limit. For example, adsorption of blood proteins can initiate the intrinsic coagulation cascade at low coverage.…”

A Random Sequential Adsorption Model for Protein Adsorption to Surfaces Functionalized with Poly(ethylene oxide)

“…[15] An application of the RSA model may also benefit a number of newly developed coating system, including ''bottle'' brushes of poly(oligo(ethylene glycol)methyl methacrylate), [32] PEOgrafted poly-(4-benzoyl-p-xylylene-co-p-xylylene) coatings, [33] and plasma-deposited tetraglyme surfaces. [34] The application of the RSA model may be limited in systems which permit the reorganization of PEO chains into ordered arrangements after the initial adsorption, because the model assumes a random placement. In principle, exchange reactions could lead to such ordering in self-assembled monolayers of alkanethiols, and interactions between PEO chains could drive ordering in physisorbed coatings.…”