Bioactive Nanogels Mimicking the Antithrombogenic Nitric Oxide‐Release Function of the Endothelium

Small, vol. 19, pp. e2205185

Abstract

Nitric oxide (NO) plays a significant role in controlling the physiology and pathophysiology of the body, including the endothelial antiplatelet function and therefore, antithrombogenic property of the blood vessels. This property of NO can be exploited to prevent thrombus formation on artificial surfaces like extracorporeal membrane oxygenators, which when come into contact with blood lead to protein adsorption and thereby platelet activation causing thrombus formation. However, NO is extremely reactive and has a very short biological half-life in blood, so only endogenous generation of NO from the blood contacting material can result into a stable and kinetically controllable local delivery of NO. In this regards, highly hydrophilic bioactive nanogels are presented which can endogenously generate NO in blood plasma from endogenous NO-donors thereby maintaining a physiological NO flux. It is shown that NO releasing nanogels could initiate cGMP-dependent protein kinase signaling followed by phosphorylation of vasodilator-stimulated phosphoprotein in platelets. This prevents platelet activation and aggregation even in presence of highly potent platelet activators like thrombin, adenosine 5'-diphosphate, and U46619 (thromboxane A2 mimetic).

Authors 8

1. Aisa Hosseinnejad Aachen

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI—Leibniz‐Institute for Interactive Materials e.V. Forckenbeckstr. 50 52056 Aachen Germany

2. Nadine Ludwig

   University of Münster · University Hospital Münster

   Affiliation as printed

   Department of Anesthesiology Intensive Care and Pain Medicine University Hospital Münster Albert‐Schweitzer‐Campus 1, Bldg. A1 48149 Münster Germany

3. Sina Mersmann

   University of Münster · University Hospital Münster

   Affiliation as printed

   Department of Anesthesiology Intensive Care and Pain Medicine University Hospital Münster Albert‐Schweitzer‐Campus 1, Bldg. A1 48149 Münster Germany

4. Patrick Winnerbach Aachen Department of Anesthesiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anesthesiology University Hospital RWTH Aachen Pauwelsstraße 30 52074 Aachen Germany

5. Christian Bleilevens Aachen Department of Anesthesiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anesthesiology University Hospital RWTH Aachen Pauwelsstraße 30 52074 Aachen Germany

6. Rolf Rossaint Aachen Department of Anesthesiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Anesthesiology University Hospital RWTH Aachen Pauwelsstraße 30 52074 Aachen Germany

7. Jan Rossaint

   University of Münster · University Hospital Münster

   Affiliation as printed

   Department of Anesthesiology Intensive Care and Pain Medicine University Hospital Münster Albert‐Schweitzer‐Campus 1, Bldg. A1 48149 Münster Germany

8. Smriti Singh corresponding Aachen

   Max Planck Institute for Medical Research · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI—Leibniz‐Institute for Interactive Materials e.V. Forckenbeckstr. 50 52056 Aachen Germany

   Max‐Planck‐Institut für medizinische Forschung Jahnstraße 29 69120 Heidelberg Germany