Stability and Thrombogenicity Analysis of Collagen/Carbon Nanotube Nanocomposite Coatings Using a Reversible Microfluidic Device

Kristina D Popovich; Sergey A Vagner; Denis T Murashko; Galina N Ten; Dmitry I Ryabkin; Mikhail S Savelyev; Evgeny P Kitsyuk; Ekaterina A Gerasimenko; Polina Edelbekova; Anton N Konovalov; Dmitry V Telyshev; Sergey V Selishchev; Alexander Yu Gerasimenko

doi:10.3390/membranes13040403

Stability and Thrombogenicity Analysis of Collagen/Carbon Nanotube Nanocomposite Coatings Using a Reversible Microfluidic Device

Membranes (Basel). 2023 Apr 1;13(4):403. doi: 10.3390/membranes13040403.

Authors

Kristina D Popovich^{1

2}, Sergey A Vagner¹, Denis T Murashko², Galina N Ten³, Dmitry I Ryabkin^{1

2}, Mikhail S Savelyev^{1

2}, Evgeny P Kitsyuk⁴, Ekaterina A Gerasimenko^{2

5}, Polina Edelbekova⁶, Anton N Konovalov⁷, Dmitry V Telyshev^{1

2}, Sergey V Selishchev², Alexander Yu Gerasimenko^{1

2}

Affiliations

¹ Institute for Bionic Technologies and Engineering, I.M. Sechenov First Moscow State Medical University, Bolshaya Pirogovskaya Street 2-4, 119435 Moscow, Russia.
² Institute of Biomedical Systems, National Research University of Electronic Technology, Shokin Square 1, Zelenograd, 124498 Moscow, Russia.
³ Department of Physics, Saratov State University, Astrakhanskaya Street 83, 410012 Saratov, Russia.
⁴ Scientific-Manufacturing Complex "Technological Centre", Shokin Square 1, bld. 7 off. 7237, 124498 Moscow, Russia.
⁵ Orthopedic Department, State Autonomous Institution of Health of the City of Moscow, Dental Clinic No.35, Building 1638, Zelenograd, 124365 Moscow, Russia.
⁶ Insitute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32a Leninsky Av., 119991 Moscow, Russia.
⁷ Burdenko Neurosurgical Center, 125047 Moscow, Russia.

Abstract

Currently, the development of stable and antithrombogenic coatings for cardiovascular implants is socially important. This is especially important for coatings exposed to high shear stress from flowing blood, such as those on ventricular assist devices. A method of layer-by-layer formation of nanocomposite coatings based on multi-walled carbon nanotubes (MWCNT) in a collagen matrix is proposed. A reversible microfluidic device with a wide range of flow shear stresses has been developed for hemodynamic experiments. The dependence of the resistance on the presence of a cross-linking agent for collagen chains in the composition of the coating was demonstrated. Optical profilometry determined that collagen/c-MWCNT and collagen/c-MWCNT/glutaraldehyde coatings obtained sufficiently high resistance to high shear stress flow. However, the collagen/c-MWCNT/glutaraldehyde coating was almost twice as resistant to a phosphate-buffered solution flow. A reversible microfluidic device made it possible to assess the level of thrombogenicity of the coatings by the level of blood albumin protein adhesion to the coatings. Raman spectroscopy demonstrated that the adhesion of albumin to collagen/c-MWCNT and collagen/c-MWCNT/glutaraldehyde coatings is 1.7 and 1.4 times lower than the adhesion of protein to a titanium surface, widely used for ventricular assist devices. Scanning electron microscopy and energy dispersive spectroscopy determined that blood protein was least detected on the collagen/c-MWCNT coating, which contained no cross-linking agent, including in comparison with the titanium surface. Thus, a reversible microfluidic device is suitable for preliminary testing of the resistance and thrombogenicity of various coatings and membranes, and nanocomposite coatings based on collagen and c-MWCNT are suitable candidates for the development of cardiovascular devices.

Keywords: adhesion; blood; bovine serum albumin; carbon nanotubes; coating; collagen; glutaraldehyde; hemocompatible membranes; microfluidic device; nanocomposite; protein; thrombogenicity.

Grants and funding

The research of hemodynamic parameters, as well as the stability and thrombogenicity of nanocomposite materials using Raman spectroscopy, was supported by the grant of the Russian Science Foundation No. 22-75-00089, https://rscf.ru/project/22-75-00089/. The research coating formation by spray deposition, electron microscopy and energy-dispersive X-ray spectroscopy was funded by the Ministry of Science and Higher Education of the Russian Federation under grant agreement No. 075-15-2021-596 (Sechenov University).