Biomimetic modification of metallic cardiovascular biomaterials: from function mimicking to endothelialization in vivo

Abstract

Biosystem-surface interactions play an important role in various biological events and determine the ultimate functionality of implanted devices. Endothelialization or mimicking of endothelium on the surface of cardiovascular materials is a promising way to solve the problems of material-induced thrombosis and restenosis. Meanwhile, a multifunctional surface design is needed as antithrombotic properties should be considered in the period when the implants are not yet completely endothelialized. In this article, we summarize some successful approaches used in our laboratory for constructing multifunctional endothelium-like surfaces on metallic cardiovascular biomaterials through chemical modification of the surface or by the introduction of specific biological molecules to induce self-endothelialization in vivo. Some directions on future research in these areas are also presented.

Keywords: biomimetic modification; endothelial cell; endothelialization; nitric oxide.

Figure 1.

Schematic figure of NO–cGMP pathway in the inhibition of platelet activation and SMC proliferation.

Figure 2.

Intimal and neointimal thickness analysis showing selenocystamine-immobilized stents (Se, striped bars) reduces the incidence of neointimal hyperplasia compared with that of stainless steel stents (SS, open bars).

Figure 3.

Representative scanning electron photomicrographs showing endothelial cell-like cells covered the surface of the selenocystamine stents. (a) Lower magnification of 100×; (b) higher magnification of the region showing cobblestone-shaped cells on the surface of stent.

Figure 4.

Production of NO by ECs cultured on the control and ECM-modified Ti. *p < 0.001 compared with the control Ti. Dotted bars, 1 day; striped bars, 3 days.

Figure 5.

Micrographs of neointima growing on the surfaces of Ti and ECM-Ti exhibited by (a) Masson's Trichrome Stains and (b) immunohistochemical stains for α-SMA and (c) vWF; scale bar, 400×.

Figure 6.

Schematic figure of oriented immobilization of anti-CD34 Ab on Ti surface.

Figure 7.

Representative scanning electron photomicrographs showing EPCs captured in vivo at 2 h after implantation (a) and (b) untreated Ti (bare Ti); (c,d) anti-CD34-coated Ti; (a,c) SEM photograph (the inset is the high magnification). (b,d) FITC-fluorescent stain for EPCs/ECs marker of VEGFR-2 showing anti-CD34 antibody-coated surface was almost fully covered with EPCs/CEs marker positive cells.

Figure 8.

A schematic figure showing biotinylated peptide aptamer conjugated to titanium. The surface of titanium was first deposited on layers of polydopamine and then reacted with avidin, which binds to BSA. The final reaction between avidin and biotinylated peptide aptamer linked the biotinylated peptide aptamer to the substrate.

Figure 9.

(a,b) Digital images and (c,d) SEM images of (a,c) Ti-O and (b,d) SS at five months post implantation. It shows a thin and transparent tissue adherent on Ti-O (a), while SS is embedded in a thick fibrin tissue capsule (b). SEM image shows typical cobblestone-shaped endothelial cells on the surface of Ti-O (c) and fibrous tissue on the surface of SS (d).