engleski

Development of Bioactive Metal Surfaces: Towards Enhancement of Biocompatibility of Coronary Stents

Angioplasty procedures followed by metallic stent implantation is currently the gold standard for minimally invasive therapy to alleviate the symptoms of coronary artery diseases. A stent is a rigid structure that prevents a vein or artery from collapsing and is typically made of 316L stainless steel. Although stenting decreases mortality and morbidity in patients suffering from vascular diseases, there are deficiencies with this implant in vivo. Namely, stent implantation causes trauma to the blood exposed vascular wall, thereby denuding the endothelial monolayer. This event can initiate the inward proliferation of smooth muscle cells (SMCs), which eventually leads to restenosis and the need for revascularization. We are going to present some recent approaches developed in our laboratories on modifying stent surfaces to improve their biocompatibility and decrease the occurrence of restenosis. It has been shown, that rapid reendothelization of the stent and surrounding vasculature after injury can significantly minimize the chances of restenosis. Thus, we hypothesize that by covalently attaching a cell adhesion protein fibronectin (FN) to the stent surface and controlling its conformation, we will be able to promote endothelial cell (EC) adhesion and proliferation on the surface, while minimizing SMC cellular activities. Initially, we used 11mercaptoundecanoic acid to irreversibly immobilize FN onto a model metallic surface (gold). By modulating the surface charge and wettability with mixed self assembled monolayers (SAMs) of various terminal functional groups at various ratios (COOH, CH3, OH and NH2), we were able to modulate the surface conformation of immobilized FN, and thus the subsequent cell/material interactions. We found that the presence of covalently bound FN on the surface significantly enhanced EC attachment and proliferation in vitro. The EC/surface interactions were found to be highly dependant on the SAM composition and the corresponding surface wettability and charge. The optimum surfaces were found to be the NH2/COOHterminated SAMs. The interactions of ECs with these surfaces were found to be enhanced relative to the SMC/surface interactions, thus indicating that FN/NH2/COOH modified stent surfaces would offer better biocompabitility (lower restenosis rate) then currently used barestent surfaces. We are presently transferring these findings on to commercial 316L stent surfaces. The principal challenge has been to form a stable SAM on the 316L surface. We have employed electrochemistrybased methods for binding COOH and NH2terminated alkanethiols on the 316L surface, and have found that these SAMs are highly stable and can be further chemically modified to bind FN. We are currently performing cell/316LFN experiments to evaluate the response of ECs and SMCs to this surface followed by in-vivo experiments in animal models.

Angioplasty; stent; implantation; 316L stainless steel; self-assembled monolayers

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