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.
Original language | English (US) |
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Article number | 121011 |
Journal | Biomaterials |
Volume | 276 |
DOIs | |
State | Published - Sep 2021 |
Externally published | Yes |
Keywords
- Anti-thrombogenic coating
- Bioactive surface
- Blood-contacting devices
- Site-specific bioconjugation
- Ultralow molecular weight heparin
- Vascular graft
ASJC Scopus subject areas
- Mechanics of Materials
- Ceramics and Composites
- Bioengineering
- Biophysics
- Biomaterials