Yanwei Wang

Combining surface topography with polymer chemistry: exploring new interfacial biological phenomena

The review focuses on the combination of surface topography and surface chemical modification with the grafting of polymer chains to develop optimal material interfaces for biological and biomedical applications. Understanding how surface chemistry and topography correlate with the interfacial properties and biological functions of a material is important for the development of biomaterials. Synergies between these two properties are known to exist, but have not been exploited extensively for biomaterial design. Preliminary studies suggest that the combination of surface topography and chemistry may not only enhance surface properties, but may also give biological properties that are opposite to those of the corresponding smooth surface, and even other unexpected biological properties. This review summarizes some recent studies in this area, mostly carried out in our own laboratory, as examples to illustrate how synergistic properties and functions may be obtained by combining surface topography with polymer chemistry. It is hoped that this review will stimulate a more thorough exploration of the topography–chemistry synergy as a means of injecting “new life” into efforts to develop novel bio-functional surfaces.

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.

Control the wettability of poly(n-isopropylacrylamide-co-1-adamantan-1-ylmethyl acrylate) modified surfaces : the more ada, the bigger impact?

Surface-initiated SET-LRP was used to synthesize polymer brush containing N-isopropylacrylamide and adamantyl acrylate using Cu(I)Cl/Me6-TREN as precursor catalyst and isopropanol/H2O as solvent. Different reaction conditions were explored to investigate the influence of different parameters (reaction time, catalyst concentration, monomer concentration) on the polymerization. Copolymers with variable 1-adamantan-1-ylmethyl acrylate (Ada) content and comparable thickness were synthesized onto silicon surfaces. Furthermore, the hydrophilic and bioactive molecule β-cyclodextrin-(mannose)7 (CDm) was synthesized and complexed with adamantane via host-guest interaction. The effect of adamantane alone and the effect of CDm together with adamantane on the wettability and thermoresponsive property of surface were investigated in detail. Experimental and molecular structure analysis showed that Ada at certain content together with CDm has the greatest impact on surface wettability. When Ada content was high (20%), copolymer-CDm surfaces showed almost no CDm complexed with Ada as the result of steric hindrance.

Aptamer-Modified Micro/Nanostructured Surfaces: Efficient Capture of Ramos Cells in Serum Environment

For potential applications in the isolation and enrichment of circulating tumor cells (CTCs), we have developed gold nanoparticle layers (GNPLs) of different roughness modified with TD05 aptamers (GNPL-APT). In serum-free binary cell mixtures containing Ramos cancer cells and CEM cells, the density of Ramos cells adherent to highly rough GNPL-APT was 19 times that of CEM cells. However, in serum-containing conditions, the specificity of GNPL-APT for Ramos cells was much reduced. To improve Ramos specificity in the presence of serum, we attached the TD05 aptamer to the layers via poly(oligo(ethylene glycol) methacrylate) (POEGMA) as an antifouling spacer (GNPL-POEGMA-APT). In serum-containing environment GNPL-POEGMA-APT showed an enhanced selectivity for Ramos cells, which increased with increasing surface roughness. The results of this study indicate that surfaces combining appropriate chemical composition and micro/nano roughness structures may be useful for cell separation, including the isolation of cancer cells for diagnosis.

Catalase-like and Peroxidase-like Catalytic Activities of Silicon Nanowire Arrays

Silicon nanowire arrays (SiNWAs) were found to have catalytic activities similar to those of biological enzymes catalase and peroxidase. Thus not only can these materials catalyze the decomposition reaction of H(2)O(2) into water and oxygen, but they can also catalyze the oxidation of o-phenylenediamine (OPD), a common substrate for peroxidases, by H(2)O(2). The presence of Si-H bonds and the morphology of the SiNWAs are found to be crucial to the occurrence of such catalytic activity. When the SiNWAs are reacted with H(2)O(2), the data from Raman spectroscopy suggests the formation of (Si-H)(2)···(O species) ((Si-H)(2)···Os), which is presumably responsible for the catalytic activity. These findings suggest the potential use of SiNWAs as enzyme mimics in medicine, biotechnology, and environmental chemistry.

Thermally responsive silicon nanowire arrays for native/denatured-protein separation

We present our findings of the selective adsorption of native and denatured proteins onto thermally responsive, native-protein resistant poly(N-isopropylacrylamide) (PNIPAAm) decorated silicon nanowire arrays (SiNWAs). The PNIPAAm-SiNWAs surface, which shows very low levels of native-protein adsorption, favors the adsorption of denatured proteins. The amount of denatured-protein adsorption is higher at temperatures above the lower critical solution temperature (LCST) of PNIPAAm. Temperature cycling surrounding the LCST, which ensures against thermal denaturation of native proteins, further increases the amount of denatured-protein adsorption. Moreover, the PNIPAAm-SiNWAs surface is able to selectively adsorb denatured protein even from mixtures of different protein species; meanwhile, the amount of native proteins in solution is kept nearly at its original level. It is believed that these results will not only enrich current understanding of protein interactions with PNIPAAm-modified SiNWAs surfaces, but may also stimulate applications of PNIPAAm-SiNWAs surfaces for native/denatured protein separation.

Improvement of Site-Directed Protein–Polymer Conjugates: High Bioactivity and Stability Using a Soft Chain-Transfer Agent

Protein has been widely applied in biotechnology and biomedicine thanks to its unique properties of high catalytic activity, outstanding receptor-ligand specificity, and controllable sequence mutability. Owing to the easily induced structural variation and thus the inactivation of protein, there has been much effort to improve the structural stability and biological activity of proteins by the use of polymers to modify protein to construct protein-polymer conjugates. However, during the conjugation of polymer to protein active center, the great loss in the original biological activity of the protein is still a serious and so far unsolved question. Here, for the purpose of preparing site-directed and highly structurally stable protein-polymer conjugate, which would possess at least a substantially similar level of biological activity as the original unmodified protein, we proposed a new strategy by using a pyridine chain-transfer agent (CTA-Py) with a soft pyridine-terminated chain for visible-light-induced reversible addition-fragmentation chain transfer (RAFT) polymerization specifically on a number of sites close to the protein active center. The results showed that all the intermediate conjugates PPa-CTA-Py at different modification sites could retain full enzymatic activities (about 110-130% of the unmodified PPa). It was demonstrated by dynamic computer simulation that introducing of CTA-Py had little interference to the protein spatial structure as compared to the popular maleimide chain-transfer agent (CTA-Ma) with rigid maleimide-terminated. Moreover, intermediate conjugates PPa-CTA-Py is facile and ready for further light polymerization under mild conditions. Final PPa-PNIPAAm conjugate produced from CTA-Py exhibited excellent temperature responsiveness and maintained its enzymatic activity even at high temperature. These highly stable and responsive protein-polymer conjugates have great potential and could be widely used in various industrial, chemical, biological, and pharmaceutical applications.

A simple, rapid one-step ELISA using antibody–antibody complex

The enzyme‐linked immunosorbent assay (ELISA) is one of the most frequently employed assays for clinical diagnostic testing and biological research. However, its time‐consuming operation is a major drawback. The present work aims to establish a one‐step ELISA method through the preparation of a primary antibody (Ab)–secondary Ab complex (Ab–Ab complex) in hopes of realizing more sensitive and faster detection of the trace amount of antigen (Ag). By controlling the mole ratio of the primary Ab to the secondary Ab, one‐step ELISA can be successfully achieved. Compared with the traditional ELISA, the one‐step ELISA could not only improve the detection sensitivity to 1 ng mL−1, but also reduce the operating time by 30%. Moreover, the signal intensity can be controlled by adjusting the ratio of the secondary Ab in the complex or by changing the color development time. This technique is further optimized to detect trace amounts of proteins adsorbed onto poly(N‐vinylpyrrolidone) (PVP)‐modified silicon surfaces (Si‐PVP), and the results are close to the radiolabeling method. It is concluded that the simple one‐step ELISA can be used for the rapid detection of trace amount of protein. The method holds promise for the clinical detection of trace Ag in solution and on low‐adsorption material surfaces.