Improved blood compatibility of rotary blood pump Sputnik by new design and novel anticoagulant surface coatings

• Applicant: Professor Dr. Thomas Groth
• Subject Area: Cardiology, Angiology ; Biomaterials ; Medical Physics, Biomedical Technology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 426037012

• Final Report Year: 2024

Final Report Abstract

Acute and chronic heart failure are major challenges in modern medicine. While transplantation of donor hearts is the best solutions, but mostly not available for a specific patient, ventricular assist devices (VAD) made of titanium alloys as implantable axial pumps have provided solutions to keep patients alive. Because of the shortage of donor organs, VAD often become the only solution for patients and hence a destination therapy. Long-term application of VAD requires systemic anticoagulation, which decreases the risk of thrombosis but increases that of bleeding. Moreover, the design of VAD bears risk of shear-induced damage of blood components, but also indevice thrombosis due to insufficient blood compatibility of metallic pump components. Therefore, we studied here strategies to improve the blood compatibility of titanium by durable covalent or adsorptive binding of heparin. Since direct binding of heparin to titanium is not possible an activation of the metal by either amino-functionalized organosilanes (OS) or phosphonates was done showing that phosphonate coupling to titanium was not stable. Therefore, OS were used for surface activation providing amino groups for side-on or end-on immobilization of heparin with the latter most favorable regarding anticoagulant activity towards factor Xa. An additional sacrificial coating of heparin was achieved by adsorption of multilayers combining cations like chitosan with anti-bacterial properties and non-fractionated heparin. The coatings were stable over periods of 3 weeks when exposed to buffer solutions. It was also evident that multilayers containing adsorptive-bound heparin were superior regarding inhibition of blood coagulation measuring partial thromboplastin and thrombin time, but also in their anti-Xa activity. On the other hand, platelet adhesion and activation were significantly lower on covalent immobilized heparin in comparison to multilayers. Finally, macrophages as key players during implant associated inflammatory responses adhered to lesser extent and showed lesser signs of activation on heparin-containing multilayers when compared to plain titanium. Overall, both covalent and adsorptive immobilization of heparin on titanium enabled by the activation with organosilanes may provide VADs or specific parts of them with an excellent local anticoagulant activity that may reduce the risk of in-device thrombosis.

Publications

• Control of Blood Coagulation by Hemocompatible Material Surfaces—A Review. Bioengineering, 8(12), 215.
  Kuchinka, Janna; Willems, Christian; Telyshev, Dmitry V. & Groth, Thomas
  
• Hemolytic Performance in Two Generations of the Sputnik Left Ventricular Assist Device: A Combined Numerical and Experimental Study. Journal of Functional Biomaterials, 13(1), 7.
  Romanova, Alexandra N.; Pugovkin, Alexander A.; Denisov, Maxim V.; Ephimov, Ivan A.; Gusev, Dmitry V.; Walter, Marian; Groth, Thomas; Bockeria, Olga L.; Le, Tatyana G.; Satyukova, Anna S.; Selishchev, Sergey V. & Telyshev, Dmitry V.
  
• Wearable and implantable artificial kidney devices for end‐stage kidney disease treatment: Current status and review. Artificial Organs, 47(4), 649-666.
  Groth, Thomas; Stegmayr, Bernd G.; Ash, Stephen R.; Kuchinka, Janna; Wieringa, Fokko P.; Fissell, William H. & Roy, Shuvo