Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Camouflaging Endovascular Stents With an Endothelial Coat Using CD31 Domain 1 Mimetic Peptides

Version 1 : Received: 27 September 2023 / Approved: 28 September 2023 / Online: 28 September 2023 (11:20:18 CEST)

How to cite: Sénémaud, J.; Skarbek, C.; Hernandez, B.; Song, R.; Pan, Z.; Lefevre, I.; Elisabetta, B.; Castier, Y.; Nicoletti, A.; Bureau, C.; Caligiuri, G. Camouflaging Endovascular Stents With an Endothelial Coat Using CD31 Domain 1 Mimetic Peptides. Preprints 2023, 2023092003. https://doi.org/10.20944/preprints202309.2003.v1 Sénémaud, J.; Skarbek, C.; Hernandez, B.; Song, R.; Pan, Z.; Lefevre, I.; Elisabetta, B.; Castier, Y.; Nicoletti, A.; Bureau, C.; Caligiuri, G. Camouflaging Endovascular Stents With an Endothelial Coat Using CD31 Domain 1 Mimetic Peptides. Preprints 2023, 2023092003. https://doi.org/10.20944/preprints202309.2003.v1

Abstract

Background: Implantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells, platelets, and circulating leukocytes. The aim of this study was to mask endovascu-lar stents with peptides imitating CD31, to mimic the device's surface to resemble that of a healthy vascular endothelium. Methods: Peptide design relied on established trans-homophilic sequences found within domains 1 and 2 of CD31. Subsequently, synthetic peptides were immobilized onto flat CoCr and nitinol discs and their impact on the primary human arterial endothelial cell phenotype was evaluated in vitro. Following this, clinical-grade CoCr and nitinol endovascular devices were coated with one of the peptides that demonstrated the capability to induce a pro-physiologic endothelial phenotype, implanted in the arteries of rabbits, and compared to un-coated controls. Results: Membrane-distal CD31 domains 1 and 2 peptides exhibited a distinct capability to foster a healthy endothelial phenotype in vitro. By day 7 post-aortic implantation, CoCr stents were evenly covered by whole-some endothelial cells, devoid of thrombo-inflammatory signs, in contrast to both bare metal and drug-eluting stents. At day 60, nitinol-coated flow diverters demonstrated enhanced performance in comparison to the control groups for excluding experimental carotid aneurysms, facilitating the formation of a seamless "neo-arterial" wall. Conclusion: Membrane-distal CD31 biomimetic peptides effectively camouflage the device surface, prevent-ing local reactions and promoting rapid and seamless endovascular integration.

Keywords

CD31 interactions; Endovascular stents; camouflage strategy; circulatory homeostasis; device integration

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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