Cardiovascular diseases represent the leading cause of death in the world. Stents are used to treat the complications that atherosclerosis causes at late stage of its progression. Made from different alloys such as stainless steel, nitinol and cobalt chromium alloys (L605), this latter has generated significant interest because it allows the fabrication of thinner devices, which have decreased post-implantation clinical complications. Nonetheless, L605 bare metal stents lacks integration with the host. Thus, enhanced biological properties, such as endothelialisation, low thrombosis activity and anti-inflammatory behaviour represent mandatory requirements for clinics. To confer these properties onto metallic devices, polymeric-based coatings, as an intermediate layer to further functionalize with bioactive molecules, are often deposited. Nonetheless, major techniques to deposit these polymeric coatings involve the use of wet-chemistry and do not ensure total resistance during the stent implantation procedure due to lack of cohesion and delamination of the polymeric layer. 

In this context, a novel approach that foregoes this previously mandatory coating step was developed. This novel approach involves the use of plasma-based techniques to create functional groups (reactive amine groups, -NH2), directly onto the metallic surface without modifying the bulk properties, that can be used as anchor points for the further grafting of bioactive molecules of interest. Finally, a bioactive peptide derived from the platelet endothelial cell adhesion molecule (PECAM-1 or CD31) was grafted, due to its potential pro-endothelialization, anti-inflammatory and anti-thrombotic behaviour. After full characterization, this pro-active coating was selected for an in vivo trial in porcine model. This strategy improved re-endothelialization after 7 days when compared to commercial drug eluting stents, with further, low adhesion of leukocytes and platelets when compared to bare metal stents. Overall, this research allowed the development and validation of a promising platform to directly immobilize bioactive molecules onto metallic cardiovascular implants, providing clear advantages of medical devices currently on the market.

References

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2. S. Diaz-Rodriguez, C. Loy, P. Chevallier, C. Noël, G. Caligiuri, L. Houssiau, D. Mantovani. Comparison of the linking arm effect on the biological performance of a CD31 agonist directly grafted on L605 CoCr alloy by a plasma-based multistep strategy. Biointerphases,  https://doi.org/10.1116/1.5120902, 2019.
3. S. Diaz-Rodriguez, P. Chevallier, C. Paternoster, V. Montaño-Machado, C. Noël, L. Houssiau, D. Mantovani. Surface modification and direct plasma amination of L605 CoCr alloys: on the optimization of the oxide layer for cardiovascular implants. RSC Advances, 9, 4, 2291-2301, 2019.
4. S. Diaz‐Rodriguez, P. Chevallier, D. Mantovani. Low‐pressure plasma treatment for direct amination of L605 CoCr alloy for the further covalent grafting of molecules. Plasma Processes and Polymers 15 (7), 1700214, 2018.