A rechargeable anti-thrombotic coating for blood-contacting devices

Biomaterials. 2021 Sep;276:121011. doi: 10.1016/j.biomaterials.2021.121011. Epub 2021 Jul 9.

Abstract

Despite the potential of anti-thrombogenic coatings, including heparinized surfaces, to improve the performance of blood-contacting devices, the inevitable deterioration of bioactivity remains an important factor in device failure and related thrombotic complications. As a consequence, the ability to restore the bioactivity of a surface coating after implantation of a blood-contacting device provides a potentially important strategy to enhance its clinical performance. Here, we report the regeneration of a multicomponent anti-thrombogenic coating through use of an evolved sortase A to mediate reversible transpeptidation. Both recombinant thrombomodulin and a chemoenzymatically synthesized ultra-low molecular weight heparin were repeatedly and selectively immobilized or removed in a sequential, alternating, or simultaneous manner. The generation of activated protein C (aPC) and inhibition of activated factor X (FXa) was consistent with the molecular composition of the surface. The fabrication of a rechargeable anti-thrombogenic surface was demonstrated on an expanded polytetrafluoroethylene (ePTFE) vascular graft with reconstitution of the surface bound coating 4 weeks after in vivo implantation in a rat model.

Keywords: Anti-thrombogenic coating; Bioactive surface; Blood-contacting devices; Site-specific bioconjugation; Ultralow molecular weight heparin; Vascular graft.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessel Prosthesis
  • Coated Materials, Biocompatible
  • Heparin*
  • Polytetrafluoroethylene
  • Rats
  • Thrombosis* / prevention & control

Substances

  • Coated Materials, Biocompatible
  • Polytetrafluoroethylene
  • Heparin