Abstract
Background: Clot formation on foreign surfaces of extracorporeal membrane oxygenation systems is a frequent event. Herein, we show an approach that mimics the enzymatic process of endogenous nitric oxide (NO) release on the oxygenator membrane via a biomimetic, non-fouling microgel coating to spatiotemporally inhibit the platelet (PLT) activation and improve antithrombotic properties. This study aims to evaluate the potential of this biomimetic coating towards NO-mediated PLT inhibition and thereby the reduction of clot formation under flow conditions. Methods: Microgel-coated (NOrel) or bare (Control) poly(4-methyl pentene) (PMP) fibers were inserted into a test channel and exposed to a short-term continuous flow of human blood. The analysis included high-resolution PLT count, pooled PLT activation via β-Thromboglobulin (β-TG) and the visualization of remnants and clots on the fibers using scanning electron microscopy (SEM). Results: In the Control group, PLT count was significantly decreased, and β-TG concentration was significantly elevated in comparison to the NOrel group. Macroscopic and microscopic visualization showed dense layers of stable clots on the bare PMP fibers, in contrast to minimal deposition of fibrin networks on the coated fibers. Conclusion: Endogenously NO-releasing microgel coating inhibits the PLT activation and reduces the clot formation on PMP fibers under dynamic flow.
Highlights
(VA-Extracorporeal membrane oxygenation (ECMO)) primarily provides circulatory support in cardiogenic shock [2], while venovenous ECMO (VV-ECMO) is mainly used in patients suffering from isolated pulmonary conditions, such as acute respiratory distress syndrome (ARDS) [3]
Microgel-coated poly(4-methyl pentene) (PMP) fibers were inserted into a test channel and exposed to a continuous flow of heparinized (2.5 IU mL−1 ) human blood for 48 min
We show that the integration of hydrophilicity and nitric oxide (NO)-release functions of the microgel coating could prevent clot formation in the flow condition, with minimally heparinized blood
Summary
Extracorporeal membrane oxygenation (ECMO) is the last therapeutic option for patients with isolated or combined acute cardiopulmonary failure [1]. The oxygenator, mainly consisting of hollow fibers, which represent the ECCs largest blood-contacting foreign surface, is the core component of an ECMO system. Hollow fibers are commonly made of hydrophobic polymers, including poly(4-methyl-1-pentene) (PMP). Clot formation on foreign surfaces of extracorporeal membrane oxygenation systems is a frequent event. We show an approach that mimics the enzymatic process of endogenous nitric oxide (NO) release on the oxygenator membrane via a biomimetic, non-fouling microgel coating to spatiotemporally inhibit the platelet (PLT) activation and improve antithrombotic properties. Methods: Microgelcoated (NOrel) or bare (Control) poly(4-methyl pentene) (PMP) fibers were inserted into a test channel and exposed to a short-term continuous flow of human blood. Macroscopic and microscopic visualization showed dense layers of stable clots on the bare PMP fibers, in contrast to minimal deposition of fibrin networks on the coated fibers
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