In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications

Abstract

Introduction: Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. Methods: The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. Results: Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. Conclusions: A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

Visualizing a Nanoscale Lubricant Layer under Blood Flow

“…Significantly, we demonstrated that these thin TLP layers prevent the adhesion of human whole blood (platelets and fibrinogen), both under static conditions (seen previously) and shear flow. These results are consistent with previous findings in the literature that reported the repellence of fibrinogen and platelets on TLP coatings. ,,, …”

“…These results are consistent with previous findings in the literature that reported the repellence of fibrinogen and platelets on TLP coatings. 8,15,38,39 TLP coatings could find clinical application in devices and components intended for short-term or transient usage and/or in devices with lower flow or stagnant flow regions. The method described here allows us to relate the performance of TLP in near-clinical flow conditions to the presence and distribution of lubricants, in settings that are challenging to characterize otherwise.…”

“…In previous studies, fibrinogen and platelet adhesion was found to be significantly reduced on TLP surfaces relative to control surfaces in a static system both in buffer 37,38 and in human whole blood. 8,39 This evidence suggests an inherent ability of the TLP surfaces to prevent the adhesion of fibrinogen and platelets under both static and flow conditions.…”

Bioinspired Approaches to Engineer Antithrombogenic Medical Devices for Vascular Intervention

“…100 In extracorporeal circuits, in vivo studies for 6 and 8 hours demonstrated the antithrombogenic properties of LIS. 103,105,108 However, on extracorporeal circuits exposed to blood for 72 hours, the coatings were reported to have failed. 109 The authors have attributed blood flow for extended durations as a possible reason, leading to the loss of lubricant, resulting in thrombus deposition.…”

A Clinical‐Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks

“…[23][24][25][26] Beyond systemic anticoagulation, most efforts to further address these complications are directed toward mitigating surface-induced activation of the blood, via application of anti-thrombotic surface treatments applied to the HFMO cartridge and to associated tubing and other circuit elements. [27][28][29] However, another major cause of hemocompatibility issues in ECMO stems from the presence of non-physiologic blood flows in the circuit [30][31][32][33] : regions of excessive shear stress, zones of blood stasis, and transition regions, all serving as a nidus for clot formation. The fundamental geometry of HFMO cartridges, in which blood flows through large bore plastic tubes and over oxygen-carrying fiber mats within a large housing, limits the ability to precisely control blood flow circulation patterns or shear rates on a local level.…”