Zhaoqiang Wu

Dual-function antibacterial surfaces for biomedical applications.

Bacterial attachment and the subsequent formation of biofilm on surfaces of synthetic materials pose a serious problem in both human healthcare and industrial applications. In recent decades, considerable attention has been paid to developing antibacterial surfaces to reduce the extent of initial bacterial attachment and thereby to prevent subsequent biofilm formation. Briefly, there are three main types of antibacterial surfaces: bactericidal surfaces, bacteria-resistant surfaces, and bacteria-release surfaces. The strategy adopted to develop each type of surface has inherent advantages and disadvantages; many efforts have been focused on the development of novel antibacterial surfaces with dual functionality. In this review, we highlight the recent progress made in the development of dual-function antibacterial surfaces for biomedical applications. These surfaces are based on the combination of two strategies into one system, which can kill attached bacteria as well as resisting or releasing bacteria. Perspectives on future research directions for the design of dual-function antibacterial surfaces are also provided.

Protein adsorption on poly(N-vinylpyrrolidone)-modified silicon surfaces prepared by surface-initiated atom transfer radical polymerization.

Well-controlled poly(N-vinylpyrrolidone) (PVP)-grafted silicon surfaces were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP) with 1,4-dioxane/water mixtures as solvents and CuCl/5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane (Me6TATD) as a catalyst. The thickness of the PVP layer on the surface increased with reaction time, suggesting that the ATRP grafting of N-vinylpyrrolidone (NVP) from the silicon surfaces was a well-controlled process. The water contact angle and X-ray photoelectron spectroscopy (XPS) were used to characterize the modified surfaces. The protein adsorption property of the PVP-grafted surfaces was evaluated using a radiolabeling method. Compared with unmodified silicon surfaces, a Si-PVP60 surface with a PVP thickness of 15.06 nm reduced the level of adsorption of fibrinogen, human serum albumin (HSA), and lysozyme by 75, 93, and 81%, respectively. Moreover, the level of fibrinogen adsorption decreases gradually with an increase in PVP thickness. However, no significant difference in fibrinogen adsorption was found when the PVP layer was thicker than the critical thickness of 13.45 nm.

Protein adsorption on poly(N-isopropylacrylamide)-modified silicon surfaces: Effects of grafted layer thickness and protein size

In this work, we investigated the protein adsorption on the end-tethered thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes with varying grafted layer thickness prepared via surface-initiated atom transfer radical polymerization (SI-ATRP) on initiator-immobilized silicon surfaces. The thickness of a grafted layer was modulated by adjusting reaction time and/or solvent composition. The surface properties as a function of thickness were investigated by water contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscope (AFM). The influence of PNIPAAm-grafted layer thickness on human serum albumin (HSA) adsorption in phosphate-buffered saline (PBS) (pH 7.4) at different temperature was evaluated using a radiolabeling method. In a lower thickness range (<15 nm), protein adsorption on PNIPAAm-grafted layer shows a thermoresponsive change in a certain extent, but the variation is not remarkable. However, it is interesting to observe that these surfaces exhibit good protein-resistant property. For the surface with a PNIPAAm thickness of 13.4 nm, the HSA adsorption level measured at room temperature was approximately 7 ng/cm2, corresponding to a reduction of 97% compared to the unmodified silicon surface. For thicker PNIPAAm-grafted surface with thickness of 38.1 nm, the adsorption results of three proteins (HSA, fibrinogen, and lysozyme) with different sizes and charges indicate that the PNIPAAm-modified surface exhibits a size-sensitive property of protein adsorption.

Poly(N-vinylpyrrolidone)-Modified Surfaces for Biomedical Applications

Poly(N-vinylpyrrolidone) (PVP), an important water soluble synthetic polymer, has many desirable properties including low toxicity, chemical stability, and good biocompatibility. Since PVP is hemocompatible and physiologically inactive, it has been used as a blood plasma substitute. Surface modification with PVP has been investigated extensively over the past few years as a means of preventing nonspecific protein adsorption. PVP may therefore be seen as a promising antifouling surface modifier comparable to poly(ethylene glycol) (PEG). In this review, various approaches for the design and preparation of PVP-modified surfaces are summarized and potential biomedical applications of these PVP-modified materials are indicated. Finally, some perspectives on future research on PVP for surface modification are discussed.

Sensitive sandwich ELISA based on a gold nanoparticle layer for cancer detection

The availability of techniques for the sensitive detection of early stage cancer is crucial for patient survival. Our previous research (Langmuir, 2011, 27, 2155-2158) showed that gold nanoparticle layers (GNPL) used in indirect format ELISA amplified the signal, and gave a lower limit of detection (LOD) compared with commercial ELISA plates. However, due to its intrinsic limitations, indirect ELISA is not suitable for samples of complex composition, such as serum, plasma, etc., thus limiting the clinical performance of this kind of ELISA. In the work reported here, a GNPL-based sandwich format ELISA was developed, which showed superiority in terms of detection limit and sensitivity in the determination of rabbit IgG in buffer. More importantly, experiments using plasma spiked with carcinoembryonic antigen (CEA) as a representative biomarker showed that our GNPL-based ELISA assay amplified the signal and lowered the LOD compared to other assays, including commercialized CEA ELISA kits. This simple and cost-effective GNPL-based sandwich ELISA holds promise in clinical applications.

Lysine–poly(2-hydroxyethyl methacrylate) modified polyurethane surface with high lysine density and fibrinolytic activity

We have developed a potentially fibrinolytic surface in which a bioinert polymer is used as a spacer to immobilize lysine such that the ε-amino group is free to capture plasminogen when in contact with blood. Adsorbed plasminogen can be activated to plasmin and potentially dissolve nascent clots formed on the surface. In previous work lysine was immobilized through a poly(ethylene glycol) (PEG) spacer; however, the graft density of PEG was limited and the resulting adsorbed quantity of plasminogen was insufficient to dissolve clots efficiently. The aim of the present work was to optimize the surface using graft-polymerized poly(2-hydroxyethyl methacrylate) (poly(HEMA)) as a spacer to increase the grafting density of lysine. Such a poly(HEMA)-lysine modified polyurethane (PU) surface is expected to have increased plasminogen binding capacity and clot lysing efficiency compared with PEG-lysine modified PU. A lysine density of 2.81 nmol cm(-2) was measured on the PU-poly(HEMA)-Lys surface vs. 0.76 nmol cm(-2) on a comparable PU-PEG-Lys surface reported previously. The poly(HEMA)-lysine-modified surface was shown to reduce non-specific (fibrinogen) adsorption while binding plasminogen from plasma with high affinity. With increased plasminogen binding capacity these surfaces showed more rapid clot lysis (20 min) in a standard in vitro assay than the corresponding PEG-lysine system (40 min). The data suggest that poly(HEMA) is superior to PEG when used as a spacer in the immobilization of bioactive molecules at high density. This method of modification may also provide a generic approach for preparing bioactive PU surfaces of high activity and low non-specific adsorption of proteins.

A Facile Approach to Modify Polyurethane Surfaces for Biomaterial Applications

In this communication, we introduce a facile and highly efficient approach for surface modification of polyurethane (PU). Double bonds were incorporated onto the PU surface using a unique monomer, methacryloyl isothiocyanate (MI). Several monomers, such as N-isopropyl acrylamide (NIPAAm) and 2-hydroxyethyl methacrylate (HEMA), were used to prove that the polymerization process can be carried out on a vinyl-functionalized surface. The protein-adsorption property of the grafted surfaces shows that protein adsorption was significantly reduced after grafting each polymer onto the PU surface. Moreover, this method can be applied to polyurethane materials with any shape, including tubes and scaffolds, for which plasma treatment and photoinitiation at the inner surface are difficult to perform.

Poly(N-vinylpyrrolidone)-modified poly(dimethylsiloxane) elastomers as anti-biofouling materials.

A new method for the modification of poly(dimethylsiloxane) (PDMS) elastomer surfaces with hydrophilic poly(N-vinylpyrrolidone) (PVP) has been developed. PVP chains were grafted from the PDMS surface by surface-initiated atom transfer radical polymerization (SI-ATRP). The resulting surfaces were characterized by X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM) and water contact angle measurements. It was shown that the modified surfaces were strongly hydrophilic, indicating that the PVP grafts dominate the surface and define its properties. The anti-fouling properties of the grafted surfaces were demonstrated in protein adsorption and cell adhesion experiments. Both protein adsorption and cell adhesion were inhibited significantly on the PVP-modified PDMS surfaces compared to unmodified controls. It is concluded that modification by SI-ATRP grafting of PVP is an effective method for the preparation of anti-biofouling PDMS materials.

Facile synthesis of thermally stable poly(N-vinylpyrrolidone)-modified gold surfaces by surface-initiated atom transfer radical polymerization.

Well-controlled polymerization of N-vinylpyrrolidone (NVP) on Au surfaces by surface-initiated atom transfer radical polymerization (SI-ATRP) was carried out at room temperature by a silanization method. Initial attempts to graft poly(N-vinylpyrrolidone) (PVP) layers from initiators attached to alkanethiol monolayers yielded PVP films with thicknesses less than 5 nm. The combined factors of the difficulty in the controllable polymerization of NVP and the instability of alkanethiol monolayers led to the difficulty in the controlled polymerization of NVP on Au surfaces. Therefore, the silanization method was employed to form an adhesion layer for initiator attachment. This method allowed well-defined ATRP polymerization to occur on Au surfaces. Water contact angle, X-ray photoelectron spectroscopy (XPS), and reflectance Fourier transform infrared (reflectance FTIR) spectroscopy were used to characterize the modified surfaces. The PVP-modified gold surface remained stable at 130 °C for 3 h, showing excellent thermal stability. Thus, postfunctionalization of polymer brushes at elevated temperatures is made possible. The silanization method was also applied to modify SPR chips and showed potential applications in biosensors and biochips.

Inhibition of protein adsorption and cell adhesion on PNIPAAm-grafted polyurethane surface: Effect of graft molecular weight

In this work, the effect of molecular weight (MW) of surface grafted poly(N-isopropylacrylamide) (PNIPAAm) on protein adsorption and cell adhesion was investigated systematically. PNIPAAm-grafted polyurethane (PU) surfaces of varying graft MW were prepared via conventional radical polymerization. The MW was controlled by adjusting the monomer concentration. Fibrinogen (Fg) and human serum albumin (HSA) were selected as model proteins and their adsorption from phosphate-buffered saline (PBS, pH 7.4) and blood plasma at 37°C was measured using a radiolabeling method and immunoblot analysis respectively. It was found that in both media, as the MW increased, the adsorption of these two proteins decreased gradually reaching a plateau value at MW above 7.9×10(4). Compared to the unmodified PU, the surface grafted with PNIPAAm of MW 14.6×10(4) reduced the adsorption of Fg and HSA in PBS by 91% and 86%, respectively. Moreover, the surfaces with higher MW PNIPAAm showed minimal adhesion of L929 cells presumably due to the absence of cell-adhesive proteins on the surfaces.