Persulfated flavonoids accelerated re-endothelialization and improved blood compatibility for vascular medical implants

Bedair, Tarek M.,Bedair, Hanan M.,Ko, Kyoung-Won,Park, Wooram,Joung, Yoon Ki,Han, Dong Keun Elsevier 2019 Colloids and Surfaces B Vol.181 No.-

<P><B>Abstract</B></P> <P>Drug-eluting stents (DESs) have been used for the treatment of cardiovascular diseases including stenosis. However, in-stent restenosis, thrombosis, and delayed re-endothelialization represent challenges for their clinical applications. Here, we demonstrate a novel work to overcome these limitations through surface modification technology. The cobalt-chromium (Co-Cr) surface was modified with antioxidants such as gallic acid (GA) and rutin (Ru) and the corresponding persulfates derivatives (<I>i.e</I>., GAS, and RuS) through a simple conjugation procedure. Various analyses tools such as ATR-FTIR, XPS, water contact angle, SEM, and AFM characterized the functionalized surface. The surface characterization confirmed that the antioxidant and the additional persulfates were successfully bonded to the Co-Cr surface. The results of <I>in vitro</I> endothelial cells proved that the persulfates derivatives showed the highest tendency to get rapid re-endothelialization especially RuS. In addition, it showed inhibition to smooth muscle cells (SMCs) as compared to control Co-Cr substrate. The persulfates modified substrates reduced the amount of adsorbed fibrinogen and albumin with higher stability to fetal bovine serum. Moreover, platelet study also demonstrated that Ru and RuS presented lower platelet adhesion with round shape morphology, whereas the control Co-Cr adhere and activate many platelets with pseudopodium morphology. Moreover, these modification processes did not cause any inflammatory responses. In conclusion, it is believed that the persulfates flavonoids have a great potential in the field of drug-eluting stents and blood contacting medical implants to improve blood compatibility, suppress SMCs, and get rapid re-endothelialization.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Antioxidants/persulfates were successfully and covalently grafted on Co-Cr substrate. </LI> <LI> The persulfated-engineered substrates present rapid re-endothelialization. </LI> <LI> Gallic acid persulfate and rutin persulfate exhibit low protein adsorption. </LI> <LI> Rutin and rutin persulfate demonstrate reduced platelet adhesion and activation. </LI> <LI> These modification processes does not cause any inflammatory responses. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Stability limit state design of box sections supporting mining and process facilities

Bedair, Osama Techno-Press 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.39 No.5

The design of box girders requires the determinations the buckling stress of the flange and the webs. Existing design equations available in codes of practice ignore the interactions between the box girder components. The paper illustrates the influence of the geometric interaction on the buckling stress of box girders. Generalized equations are first derived in terms of the web the flange geometric properties. Industrial examples are then presented showing the variation of the flange buckling stress for various stiffening configurations. The influence of the flange/web proportions on the buckling stress of box girder components is also highlighted. It is shown that buckling strength of the flange is largely affected by the restraints imposed by the webs or attached diaphragms. Graphs are presented showing various limiting states of box girders. These graphs are useful to use in practice in order to achieve economical and efficient design of box girders and rationally predict local buckling stress.

Coating defects in polymer-coated drug-eluting stents

Bedair, Tarek M.,Cho, Youngjin,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun Techno-Press 2014 Biomaterials and biomedical engineering Vol.1 No.3

Vascular stenting has a great attention as a treatment for coronary arteries diseases as compared with percutaneous balloon angioplasty. In-stent restenosis and thrombosis are side effects resulting from using bare metal stent (BMS). Employing platelet therapy allowed to reduce the rate of thrombosis, however, the rate of restenosis remains a major problem. In 2002, drug-eluting stents (DESs) were introduced as an effort to reduce the restenosis. The commercially available DESs continue to suffer from coating defects that might lead to a series of adverse effects. Most importantly, multiple concerns remain regarding the polymer coating integrity on metal surfaces or the relation of polymer irregularities to longterm adverse events.

On the post-buckling behaviour of plates under stress gradient

Bedair, Osama K. Techno-Press 1996 Structural Engineering and Mechanics, An Int'l Jou Vol.4 No.4

In this paper the elastic post-buckling behaviour of plates under non-uniform compressive edge stress is investigated. The compatibility differential equations is first solved analytically and then an approximate solution of the equilibrium equation is obtained using the Galerkin method. Explicit expressions are derived for the load-deflection, ultimate strength and membrane stress distributions. Analytical effective width formulations, based on the characteristics of the stress field of the buckled plate, are proposed for this general loading condition. The predicted load-deflection expression is compared with independent test results. Results are also presented detailing the load-deflection behaviour and stress distribution for various aspect ratios.

Buckling behaviour of plates partially restrained against rotation under stress gradient

Bedair, Osama K. Techno-Press 1996 Structural Engineering and Mechanics, An Int'l Jou Vol.4 No.4

In this paper, the behavior of plates partially restrained against rotation under stress gradient is investigated. As a first stage, an energy formulation is presented to model this boundary condition and a general expression is derived for the prediction of the elastic buckling of the plate under this general loading condition. The accuracy of the derived expression is compared numerically using the Galerkin method with other available data for the two limiting conditions of rotationally free and clamped boundaries. Results show that the prediction is within a 5% difference. The influence of rotational restraint and stress gradient upon the buckling load and the associated buckling mode is investigated. Numerical results show sensitivity of the buckling mode to the degree of rotational restraint and the variation of the buckling load with the stress gradient.

Biodegradable polymer brush as nanocoupled interface for improving the durability of polymer coating on metal surface

Bedair, T.M.,Cho, Y.,Joung, Y.K.,Han, D.K. Elsevier 2014 Colloids and Surfaces B Vol.122 No.-

Metal-based drug-eluting stents (DESs) have severe drawbacks such as peeling-off and cracking of the coated polymer. To prevent the fracture of polymer-coated layer and improve the durability of DES, poly(l-lactide) (PLLA) brushes were synthesized onto cobalt-chromium (Co-Cr or CC) surface through atom transfer radical polymerization (ATRP) of 2-hydroxyethylmethacrylate (HEMA) followed by surface-initiated ring opening polymerization (SI-ROP) of l-lactide. The polymer brushes were then characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR), water contact angle, ellipsometry, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). All of the unmodified and modified Co-Cr surfaces were coated with a matrix of poly(d,l-lactide) (PDLLA) and sirolimus (SRL). The in vitro drug release profile was measured for 70 days. The PLLA-modified Co-Cr showed a biphasic release pattern in the initial burst followed by a slow release. On the other hand, the unmodified Co-Cr showed fast drug release and detachment of the coated polymer layer due to the instability of the polymer layer on Co-Cr surface. In comparison, the PLLA-modified Co-Cr preserved a uniform coating without detachment even after 6 weeks of degradation test. The platelet morphology and low density of platelet adhered on the modified layer and the SRL-in-PDLLA coated Co-Cr surfaces demonstrated that these samples would be blood compatible. Therefore, the introduction of PLLA brush onto Co-Cr surface is proved to dramatically improve the durability of the coating layer, and it is a promising strategy to prevent the coating defects found in DESs.

Effect of lateral restraint on the buckling behaviour of plates under non-uniform edge compression

Bedair, Osama K. Techno-Press 1997 Structural Engineering and Mechanics, An Int'l Jou Vol.5 No.1

The paper investigates the influence of lateral restraint on the buckling behaviour of plate under non-uniform compression. The unloaded edges are assumed to be partially restrained against translation in the plane of the plate and the distributions of the resulting forces acting on the plate are shown. The stability analysis is done numerically using the Galerkin method and various strategies the economize the numerical implementation are presented. Results are obtained showing the variation of the buckling load, from free edge translation to fully restrained, with unloaded edges simply supported, clamped and partially restrained against rotation for various plate aspect ratios and stress gradient coefficients. An apparent decrease in the buckling load is observed due to these destabilizing forces acting in the plate and changes in the buckling modes are observed by increasing the intensity of the lateral restraint. A comparison is made between the budding loads predicted from various formulas in stability standards based on free edge translation and the values derived from the present investigation. A difference of about 34% in the predicted buckling load and different buckling mode were found.

Coating defects in polymer-coated drug-eluting stents

Bedair, Tarek M.,Cho, Youngjin,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun Techno-Press 2014 Biomaterials and Biomechanics in Bioengineering Vol.1 No.3

Vascular stenting has a great attention as a treatment for coronary arteries diseases as compared with percutaneous balloon angioplasty. In-stent restenosis and thrombosis are side effects resulting from using bare metal stent (BMS). Employing platelet therapy allowed to reduce the rate of thrombosis, however, the rate of restenosis remains a major problem. In 2002, drug-eluting stents (DESs) were introduced as an effort to reduce the restenosis. The commercially available DESs continue to suffer from coating defects that might lead to a series of adverse effects. Most importantly, multiple concerns remain regarding the polymer coating integrity on metal surfaces or the relation of polymer irregularities to longterm adverse events.

Reinforcement of Interfacial Adhesion of a Coated Polymer Layer on a Cobalt–Chromium Surface for Drug-Eluting Stents

Bedair, Tarek M.,Cho, Youngjin,Kim, Tae Jung,Kim, Young Dong,Park, Bang Ju,Joung, Yoon Ki,Han, Dong Keun American Chemical Society 2014 Langmuir Vol.30 No.27

<P>During the balloon expansion of several commercially available drug-eluting stents, various types of defects in the polymer layer have been observed. The aim of this study is to prevent these defects by increasing the interfacial adhesion between the metal substrate and the drug-in-polymer matrix using poly(caprolactone) (PCL) brushes onto a cobalt–chromium (Co–Cr or CC) alloy surface. The chemical modification of the Co–Cr surface was accomplished by grafting ricinoleic acid (RA) onto the metal substrate followed by surface-initiated ring opening polymerization of ε-caprolactone. The unmodified, RA-grafted (CC-RA), and PCL-grafted Co–Cr substrates (CC-RA-PCL3D and CC-RA-PCL6D) were characterized by various surface analyses. Poly(<SMALL>d</SMALL>,<SMALL>l</SMALL>-lactide) containing sirolimus was spray coated onto the unmodified and modified substrates. The adhesion property of the polymer coating on the PCL-grafted surfaces was improved compared to those of other samples. Among all of the drug-in-polymer coated samples, both CC-RA-PCL3D and CC-RA-PCL6D exhibited a stabilized drug release profile over 49 days. It was also revealed that CC-RA-PCL6D showed the slowest drug release of all the samples. On the basis of these results, the proposed nanocoupling method has shown not only improved adhesion of the drug-in-polymer matrix to the Co–Cr substrate but also controlled drug release.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2014/langd5.2014.30.issue-27/la501990p/production/images/medium/la-2014-01990p_0009.gif'></P>

Dual-Layer Coated Drug-Eluting Stents with Improved Degradation Morphology and Controlled Drug Release

Bedair, Tarek M.,Park, Wooram,Park, Bang-Ju,Moon, Myoung-Woon,Lee, Kwang-Ryeol,Joung, Yoon Ki,Han, Dong Keun The Polymer Society of Korea 2018 Macromolecular Research Vol.26 No.7

Drug-eluting stents (DESs) are used to treat cardiovascular diseases such as atherosclerosis. The anti-proliferative drug released from the DES suppress the proliferation of smooth muscle cells and reduced in-stent restenosis. However, a burst release of the drug in the early stages and degradation morphology of the polymer coating represent major disadvantages, which might increase the incidence of in-stent restenosis and/or thrombosis under in vivo clinical studies. To solve these problems, in this study, a double-layer coating system composed of poly(lactide) (PLLA) bottom layer and poly(lactide-co-glycolide) (PLGA) top layer are used for the fabrication of DES. PLLA bottom layer was firstly coated on the metal surface followed by oxygen ion beam treatment. It was found that increasing the ion beam exposure time, increased the roughness of PLLA surface with a nanoscale pocket (or hole)-like structure. The top layer coating represented a mixture of PLGA and paclitaxel (PTX) with 5, 10, and 20% PTX contents. The coating was performed through ultrasonic spray technique, and the morphology showed not only a smooth and uniform surface but also no irregularities were observed at zero day. The drug release and degradation morphology for single-layer (PLGA/PTX) and double-layer (PLLA/PLGA/PTX) coatings were compared. The drug release from the double-layer stainless steel (SS) group showed a slower and controlled drug release for all PTX content samples as compared to single-layer SS group. Moreover, the degradation morphology of double-layer SS group presented a smoother and uniform surface after 12 weeks of degradation under physiological conditions. Therefore, an oxygen ion beam technique with double-layer coating system could effectively control the drug release, i.e., prevent initial burst drug release, and improve the degradation morphology of biodegradable polymer-based DESs.