Citric acid functionalized nitinol stent surface promotes endothelial cell healing

Abstract

While drug‐eluting stents containing anti‐proliferative agents inhibit proliferation of smooth muscle cells (SMCs), they also delay the regrowth of the endothelial cells which can result in subsequent development of restenosis. Acidic extracellular environments promote cell anchorage and migration by inducing conformational change in integrins, the main cell adhesion proteins. This study addresses the feasibility of a citric acid (CA) functionalized nitinol stent for improving vascular biocompatibility, specifically enhancing endothelialization. CA functionalized nitinol vascular stents are compared to commercial bare metal (Zilver Flex) and paclitaxel eluting stents (Zilver PTX) in terms of re‐endothelialization. To study the effect of stent coatings, a stent conditioned media methodology was developed in an attempt to represent in vivo conditions. Overall, distinct advantages of the CA functionalized nitinol stent over commercial Zilver PTX DES and Zilver Flex BMS stents in terms of endothelial cell adhesion, migration, and proliferation are reported. These novel findings indicate the potential of a CA functionalized stent to serve as a bioactive and therapeutic surface for re‐endothelialization, perhaps in combination with a SMC proliferation inhibitor coating, to prevent restenosis.

Titanium Dioxide Covalently Immobilized Citric Acid (TiO2‐CA) Nanohybrid Coating of Neurovascular Flow Diverter to Improve Antithrombogenic and Pro‐Endothelialization Properties

“…First, the CA molecule can mimic the RGD sequence, in particular the acidic Asp residue which plays a key role in binding integrin for endothelial adhesion and proliferation. [ 42 ] Previous studies have demonstrated that CA molecules can upregulate CD31 and VEGF in HUVECs to promote the migration and tube‐formation of ECs; [ 43 ] additionally, it can suppress the release of lactate dehydrogenase (LDH) in HUVECs to inhibit their apoptosis as well as promote their proliferation. [ 33 ] Likewise, TiO 2 is also reportedly biocompatible with ECs and facilitates re‐endothelialization.…”