Yajun Weng

Immobilization of selenocystamine on TiO2 surfaces for in situ catalytic generation of nitric oxide and potential application in intravascular stents

Immobilization of selenocystamine on TiO(2) film deposited on silicon wafer and 316 stainless steel stents for catalytic generation of nitric oxide was described. Polydopamine was used as the linker for immobilization of selenocystamine to the TiO(2) surface. In vitro stability of the immobilized selenocystamine was investigated and the result shows surface selenium loss occurs mostly in the first four weeks. The selenocystamine immobilized surface possesses glutathione peroxidase (GPx) activity, and the activity increases with the amount of grafted polydopamine. Such selenocystamine immobilized surfaces show the ability of catalytically decomposing endogenous S-nitrosothiols (RSNO), generating NO; thus the surface displays the ability to inhibit collagen-induced platelet acitivation and aggregation. Additionally, smooth muscle cells are inhibited from adhering to the selenocystamine immobilized sample when RSNO is added to the culture media. ELISA analysis reveals that cGMP in both platelets and smooth muscle cells significantly increases with NO release on selenocystamine immobilized samples. Two months in vivo results show that selenocystamine immobilized stents are endothelialized, and show significant anti-proliferation properties, indicating that this is a favorable method for potential application in vascular stents.

In Vitro Investigation of Enhanced Hemocompatibility and Endothelial Cell Proliferation Associated with Quinone-Rich Polydopamine Coating

Recent investigations have demonstrated that polydopamine (PDA)-modified surfaces were beneficial to the proliferation of endothelial cells (ECs). In this work, PDA coated 316L stainless steels (316L SS) were thermally treated at 50, 100, and 150 °C respectively (hereafter designated as Th50, Th100, and Th150) and consequently produced diverse surface chemical components. In vitro hemocompatibility and vascular cell-material interactions with ECs and smooth muscle cells (SMCs) affected by surface characteristics have been investigated. The Th150, rich in quinone, showed the best hemocompatibility and could effectively inhibit platelet adhesion, activation, and fibrinogen conformation transition. The polydopamine-modified surfaces were found to induce dramatic cell-material interaction with enhanced ECs proliferation, viability and migration, release of nitric oxide (NO), and reduced SMCs proliferation. The inhibitory effect of SMCs proliferation might be associated with the surface catechol content. The coating on Th150 showed a good resistance to the deformation of compression and expansion of vascular stents. These results effectively suggested that the Th150 coating might be promising when served as a stent coating platform.

Improved immobilization of biomolecules to quinone-rich polydopamine for efficient surface functionalization

Polydopamine (PDA), a bio-inspired polymer, has been very attractive for diverse functional applications by immobilizing biomolecules. In this work, a novel approach of using PDA for improved biomolecule immobilization was developed. A thin PDA layer was strategically coated onto 316L stainless steel and thermally treated at 150°C (PDA-Th150). Subsequently, amino-terminated polyethylene glycol (mPEG-NH2) or vascular endothelial growth factor (VEGF) was immobilized onto PDA and PDA-Th150 surface. The results of attenuated total reflection-Fourier transform-infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) showed higher coverage of quinine on PDA-Th150 surface. The functionalized PDA-Th150 significantly improved its ability of immobilizing mPEG-NH2 or VEGF, as shown by platelet adhesion test and endothelial cell proliferation experiments. This novel approach may also be used for efficient immobilization of biomolecules on different metal devices.

Preparation and in vitro release profiles of drug-eluting controlled biodegradable polymer coating stents.

In the present study, the different drug-eluting controlled biodegradable polymer coatings were fabricated on stainless steel stents. The coatings were not only uniform and smooth but also had excellent mechanical property. The drug release profiles of drug-eluting stents were studied in detail in this study. Depending on the drug type, different drug-eluting stents exhibited different drug release profile. There were two basic release profiles for different drug-eluting stents, i.e., two-phase release profile with burst release or linear release profile without burst release. Incorporating heparin in the rapamycin or curcumin eluting stents can improve the average drug release rate of both and the burst release of rapamycin. The average drug release rate increased with the increase of drug loading but was not proportional to increase of the ratio of drug/polymer. Fabricating the control release layer on rapamycin-eluting stent surface can prevent the burst release of rapamycin and prolong the release period of rapamycin. All results showed that the drug release profile of drug-eluting stents depends on many parameters including drug type, ratio of drug/polymer, and drug carrier properties.

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

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.

New strategies for developing cardiovascular stent surfaces with novel functions (Review)

In this review, the authors summarize the developments in surface modification of cardiovascular materials especially in authors laboratory. The authors focus on three different strategies to construct multifunctional surfaces including coimmobilization of various biomolecules on stent surfaces, stem cell based therapy systems, and a single-molecule multipurpose modification strategy in vascular interventional therapy. The roles of various molecules like heparin, gallic acid, various aptamers, and nitric oxide are highlighted in the new strategies for developing cardiovascular stent surfaces with novel functions including excellent hemocompatibility, inhibiting smooth muscle cells proliferation, and native endothelium regeneration. The success of these multifunctional surfaces provides the tremendous potential in designing the next generation of vascular stents.

Chirality-mediated enhancement of nitric oxide release and regulation of endothelial cells behaviors by cystine immobilization on Ti–O films

Endogenous nitric oxide (NO), generated by endothelial cells (ECs), plays a critical role in the cardiovascular system. However, the effect of biomaterial-induced NO release on ECs is not clear. In this study, cystine with different chirality was immobilized on Ti–O films to catalyze endogenous S-nitrosothiol decomposition to generate NO. Chemiluminescence analysis showed that a stable, sustained release of NO at a speed similar to that in healthy ECs was achieved on both enantiomer immobilized surfaces. However, L-cystine-immobilized surfaces induced higher NO release than D-cystine-immobilized surfaces. Although BSA adsorption was enhanced on L-surfaces, according to QCM analysis, preadsorption of BSA on L-surface still had a significantly higher NO release than that on the D-surface, indicating that the adsorption of BSA on L-surfaces was reversible. Platelet activation on the L-surfaces was obviously inhibited because of induction of more NO release. The growth, migration, and NO secretion behaviors of ECs were promoted by increased NO release on the L-surfaces. These results show that L-cystine-immobilized surfaces are beneficial for the induction of NO release and regulation of the behaviors of ECs, providing a promising method for the endothelialization of vascular biomaterials.