Chong Cheng

Biopolymer functionalized reduced graphene oxide with enhanced biocompatibility via mussel inspired coatings/anchors

A green and facile method for preparing biopolymer functionalized reduced graphene oxide (RGO) by using mussel inspired dopamine (DA) as the reducing reagent and the functionalized molecule is proposed. In the study, GO is reduced by DA and DA is adhered to RGO by one-step pH-induced polymerization of DA (polydopamine, PDA), and then heparin or protein is grafted onto the PDA adhered RGO (pRGO) through catechol chemistry. The obtained pRGO, heparin grafted pRGO (Hep-g-pRGO), and BSA grafted pRGO (BSA-g-pRGO) exhibit fine 2D morphology and excellent stability in water and PBS solution. Furthermore, the biocompatibility of the biopolymer functionalized RGO are investigated using human blood cells and human umbilical vein endothelial cells (HUVECs). The biopolymer functionalized RGO exhibits an ultralow hemolysis ratio (lower than 1.8%), and the cellular toxicity assay suggests that the biopolymer functionalized RGO has good cytocompatibility for HUVEC cells, even at a high concentration of 100 μg mL-1. Moreover, the high anticoagulant ability of Hep-g-pRGO indicates that the grafted biopolymer could maintain its biological activity after immobilization onto the surface of pRGO. Therefore, the proposed safe and green biomimetic method confers the biopolymer functionalized RGO with great potential for various biological and biomedical applications.

Preparation of silver nanoparticles with antimicrobial activities and the researches of their biocompatibilities.

Silver nanoparticles were prepared by chemical reduction method using chitosan as stabilizer and ascorbic acid as reducing agent in this work. The silver/chitosan nanocomposites were characterized in terms of their particle sizes and morphology by using UV spectrophotometer, nano-grainsize analyzer, and transmission electron microscopy. Antibacterial activities of these nanocomposites were carried out for Staphylococcus aureus and Escherichia coli. The silver nanoparticles exhibited significantly inhibition capacity towards these bacteria. Detailed studies on the biocompatibility of the silver/chitosan nanocomposites were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell adhesion test. The results indicated that these silver/chitosan nanocomposites were benefit for the proliferation and adhesion of L-929 cells, and the biocompatibilities between the nanocomposites and the cells would become better with the culturing days. We anticipated that these silver/chitosan nanocomposites could be a promising candidate as coating material in biomedical engineering and food packing fields wherein antibacterial properties and biocompatibilities are crucial.

Mussel-inspired self-coating at macro-interface with improved biocompatibility and bioactivity via dopamine grafted heparin-like polymers and heparin

In this study, multifunctional mussel-inspired self-coated membranes with remarkable blood and cell compatibilities are prepared by a facile and green approach. A highly sulfonated linear heparin-like polymer (HepLP, poly(sodium 4-vinylbenzenesulfonate)-co-poly(sodium methacrylate)) and heparin are chosen for the mussel-inspired heparin-mimicking coating, respectively. Firstly, DA is grafted onto the backbone of HepLP or heparin to obtain DA grafted HepLP (DA-g-HepLP) or DA grafted heparin (DA-g-Hep) by means of the carbodiimide chemistry method. Then, the DA-g-HepLP and DA-g-Hep are used to prepare surface coated heparin-mimicking substrates; the polyethersulfone (PES) dialysis membrane is chosen as the model substrate. The coated surface composition, surface morphology, water contact angle, surface zeta-potential, blood compatibility and cell compatibility are systematically investigated. The results of surface spectra, scanning electron microscopy (SEM) and atomic force microscopy (AFM) indicated that the DA-g-HepLP and DA-g-Hep were successfully coated onto the membranes. The coated membranes showed increased hydrophilicity and electronegativity, decreased plasma protein adsorption, and suppressed platelet adhesion compared to the pristine membrane. The cell morphology observation and cytotoxicity assays demonstrated that the surface coated heparin-mimicking membranes showed superior performance in endothelial cell proliferation and morphology differentiation. In addition, the excellent anticoagulant bioactivities indicated that the adhered DA-g-HepLP (or DA-g-Hep) could function or maintain its biological activity after the immobilization. In general, the mussel-inspired protocol of surface self-coating conferred the modified membranes with integrated blood compatibility, cell proliferation and biological activity for multi-biomedical applications, like hemodialysis, blood purification, organ implantation, and cell and tissue cultures.

General and Biomimetic Approach to Biopolymer-Functionalized Graphene Oxide Nanosheet through Adhesive Dopamine

Graphene oxide (GO), reduced graphene oxide (rGO), and their derivatives are investigated for various biomedical applications explosively. However, the defective biocompatibility was also recognized, which restricted their potential applications as biomaterials. In this study, a facile biomimetic approach for preparation of biopolymer adhered GO (rGO) with controllable 2D morphology and excellent biocompatibility was proposed. Mussel-inspired adhesive molecule dopamine (DA) was grafted onto heparin backbone to obtain DA grafted heparin (DA-g-Hep) by carbodiimide chemistry method; then, DA-g-Hep was used to prepare heparin-adhered GO (Hep-a-GO) and heparin-adhered rGO (Hep-a-rGO). The obtained heparin-adhered GO (rGO) showed controllable 2D morphology, ultrastable property in aqueous solution, and high drug and dye loading capacity. Furthermore, the biocompatibility of the heparin-adhered GO (rGO) was investigated using human blood cells and human umbilical vein endothelial cells, which indicated that the as-prepared heparin-adhered GO (rGO) exhibited ultralow hemolysis ratio (lower than 1.2%) and high cell viability. Moreover, the highly anticoagulant bioactivity indicated that the adhered heparin could maintain its biological activity after immobilization onto the surface of GO (rGO). The excellent biocompatibility and high bioactivity of the heparin-adhered GO (rGO) might confer its great potentials for various biomedical applications.

Toward 3D graphene oxide gels based adsorbents for high-efficient water treatment via the promotion of biopolymers.

Recent studies showed that graphene oxide (GO) presented high adsorption capacities to various water contaminants. However, the needed centrifugation after adsorption and the potential biological toxicity of GO restricted its applications in wastewater treatment. In this study, a facile method is provided by using biopolymers to mediate and synthesize 3D GO based gels. The obtained hybrid gels present well-defined and interconnected 3D porous network, which allows the adsorbate molecules to diffuse easily into the adsorbent. The adsorption experiments indicate that the obtained porous GO-biopolymer gels can efficiently remove cationic dyes and heavy metal ions from wastewater. Methylene blue (MB) and methyl violet (MV), two cationic dyes, are chosen as model adsorbates to investigate the adsorption capability and desorption ratio; meanwhile, the influence of contacting time, initial concentration, and pH value on the adsorption capacity of the prepared GO-biopolymer gels are also studied. The GO-biopolymer gels displayed an adsorption capacity as high as 1100 mg/g for MB dye and 1350 mg/g for MV dye, respectively. Furthermore, the adsorption kinetics and isotherms of the MB were studied in details. The experimental data of MB adsorption fitted well with the pseudo-second-order kinetic model and the Langmuir isotherm, and the results indicated that the adsorption process was controlled by the intraparticle diffusion. Moreover, the adsorption data revealed that the porous GO-biopolymer gels showed good selective adsorbability to cationic dyes and metal ions.

Polyaniline‐Coupled Multifunctional 2D Metal Oxide/Hydroxide Graphene Nanohybrids

Owing to their unique properties compared with conventional bulk analogues, two-dimensional (2D) nanomaterials, having nano-scale thickness and infinite length, are attracting increasing attention for their potential application in the fields of electronics, sensing, energy storage, and conversion. In particular, transition-metal chalcogenides and metal oxide nanosheets are highly promising functional 2D nanomaterials, however, their synthesis in a large scale remains a great challenge. Graphene, a 2D “aromatic” monolayer of carbon material having an ultralight weight, high surface area, and electric conductivity, has emerged as an ideal substrate for the growth and anchoring of functional nanomaterials, such as metal oxide/hydroxide nanoparticles (MO/MH NPs). 17–19] The strong coupling between MO/MH NPs and graphene in a confined 2D manner gives nanohybrids with unique structural features and synergistic physical and electrochemical properties derived from both counterparts. Along this line, numerous 2D functional nanohybrids comprising MO/MH NPs and graphene have been successfully constructed. Nevertheless, owing to the general incompatibility between graphene and inorganic NPs under synthetic conditions, the growth of MO/MH NPs on a graphene substrate with uniform morphology, controllable particle size, and enhanced coupling effects constitutes a highly desirable synthetic target. Polyaniline (PANI) is a typical low-cost conducting polymer that can be readily shaped into multiform morphologies, such as fibers/tubes, dots/shells, and other oriented nanostructures. Hydrothermal treatment has proven to be an excellent strategy for fabricating PANI NPs. Therefore, given that the protonated nitrogen atoms in PANI can bind with metal ions and mediate their hydrolysis process during hydrothermal treatment, we imagined that graphene-supported PANI nanosheets can facilitate the growth of MO and MH nanocrystals, and thus give rise to ternary nanohybrid sheets with a uniform distribution of hybrid NPs. Herein, we demonstrate an efficient and universal strategy for the controlled growth of MO/MH (such as Co3O4, Fe2O3, and Ni(OH)2) NPs on graphene to construct unique 2D nanohybrids employing PANI as the coupling linker between the two components. These nanohybrids have a welldefined 2D morphology, confined MO/MH NPs within the PANI nanostructures, controllable particle size, and high specific surface areas. The fabricated ternary hybrids of graphene, PANI, and Co3O4 (G-PANI-Co3O4) with a particle size of 6 to 10 nm deliver excellent rate capability and cycle performance when used as electrode materials for supercapacitors. Further, thermal treatment of G-PANI-MOs/MHs under inert gas yields nitrogen-doped carbon nanosheets integrated with size-controlled metal NPs (GNC-M). For example, N-doped carbon nanosheets supported by 3 to 5 nm sized cobalt NPs (GNC-Co) are synthesized by pyrolysis of GPANI-Co3O4. The GNC-Co nanohybrids exhibit outstanding catalytic behavior for the oxygen-reduction reaction (ORR). The overall synthetic strategy of 2D ternary graphene, PANI, and MO/MH (G-PANI-MOs/MHs)-coupled nanohybrids is illustrated in Figure 1a. First, graphene oxide (GO) nanosheets were functionalized with polyaniline by in situ polymerization of aniline in a GO suspension, which led to the formation of GO-based polyaniline (GO-PANI) nanosheets after centrifugation. Second, at pH 7 the GO-PANI nanosheets were mixed with the corresponding metal salts as the precursors of MO/MH followed by hydrothermal treatment. During this process, PANI particles formed on the graphene surface, while MO/MH NPs grew simultaneously and were confined within the PANI nanostructures. Specifically, G-PANI-Co3O4 (1:3), G-PANI-Co3O4 (1:10), and GPANI-Co3O4 (1:20) were fabricated using GO-PANI with different GO to aniline weight ratios of 1:3, 1:10, and 1:20 respectively, in the first step of the synthesis. By the similar means, graphene decorated with PANI-Fe2O3 hybrid NPs (GPANI-Fe2O3 (1:10)) and PANI-Ni(OH)2 hybrid NPs (GPANI-Ni(OH)2 (1:10)) were also synthesized. For comparison, GO-PANI nanosheets were directly treated under the same conditions with no addition of metal salts, the composites obtained were named G-PANI. The morphology and microstructures of as-prepared GOPANI, G-PANI, G-PANI-Co3O4 (1:3), G-PANI-Co3O4 (1:10), [*] S. Li, Dr. Y. Su School of Aeronautics and Astronautics Shanghai Jiao Tong University 800 Dongchuan Road, Shanghai 200240 (P.R. China) E-mail: yzsu@sjtu.edu.cn

Functional Graphene Nanomaterials Based Architectures: Biointeractions, Fabrications, and Emerging Biological Applications

Functional graphene nanomaterials (FGNs) are fast emerging materials with extremely unique physical and chemical properties and physiological ability to interfere and/or interact with bioorganisms; as a result, FGNs present manifold possibilities for diverse biological applications. Beyond their use in drug/gene delivery, phototherapy, and bioimaging, recent studies have revealed that FGNs can significantly promote interfacial biointeractions, in particular, with proteins, mammalian cells/stem cells, and microbials. FGNs can adsorb and concentrate nutrition factors including proteins from physiological media. This accelerates the formation of extracellular matrix, which eventually promotes cell colonization by providing a more beneficial microenvironment for cell adhesion and growth. Furthermore, FGNs can also interact with cocultured cells by physical or chemical stimulation, which significantly mediate their cellular signaling and biological performance. In this review, we elucidate FGNs-bioorganism interactions and summarize recent advancements on designing FGN-based two-dimensional and three-dimensional architectures as multifunctional biological platforms. We have also discussed the representative biological applications regarding these FGN-based bioactive architectures. Furthermore, the future perspectives and emerging challenges will also be highlighted. Due to the lack of comprehensive reviews in this emerging field, this review may catch great interest and inspire many new opportunities across a broad range of disciplines.

Progress in heparin and heparin-like/mimicking polymer-functionalized biomedical membranes

Research into the design of heparin and heparin-like/mimicking polymer-functionalized biomedical membranes is of tremendous interest to the biomedical sector in particular and is driven by potential diverse biomedical applications such as blood purification, artificial organs and other clinical medical devices. In this review, we highlight the progress of the recent research and propose potential biomedical applications in the fields of surface heparinization and the heparin-inspired modification of polymeric membranes. We summarize various surface heparinization strategies such as blending, surface coating, grafting, layer-by-layer assembly and mussel-inspired coating. Then, we classify the heparin-like/mimicking polymers and their applications in the design of heparin-mimicking biomedical membranes and draw some conclusions. The general concept of heparin-like/mimicking polymers is usually defined as heparan sulfates or synthetic sulfated/carboxylated polymers with comparable biologically mimicking functionalities as heparin, especially anticoagulant activity. Moreover, the potential biomedical applications and benefits of heparin and heparin-like/mimicking polymer-functionalized membranes in blood purification, artificial organs and tissue engineering are also discussed in each section. The heparin and heparin-like/mimicking polymer-functionalized membranes presented are exceptional candidates for the treatment of organ failure and many other blood-contacting fields. Finally, we conclude with the challenges and future perspectives for the strategies toward the heparinization and heparin-like/mimicking modification of membrane surfaces. It is believed that this review will evoke more attention towards the design of heparinized and heparin-like/mimicking membranes and encourage future advancements of this emerging research field.

Biologically inspired membrane design with a heparin-like interface: prolonged blood coagulation, inhibited complement activation, and bio-artificial liver related cell proliferation

In the present work, inspired by the chemical structure of heparin molecules, we designed a polyethersulfone (PES) membrane with a heparin-like surface for the first time by physically blending sulfonated polyethersulfone (SPES), carboxylic polyethersulfone (CPES), and PES at rational ratios. Evaporation and phase-inversion membranes of PES/CPES/SPES were prepared by evaporating the solvent in a vacuum oven, and by a liquid-liquid phase separation technique, respectively. Scanning electron microscopy (SEM) images revealed that the structures of the PES/CPES/SPES membranes were dependent on the proportions of the additives and no obvious phase separation was detected. The blood compatibility of the modified membrane surfaces was characterized in terms of bovine serum fibrinogen (BFG) adsorption, platelet adhesion, thrombin-antithrombin (TAT) generation, percentage of platelets positive for CD62p expression, clotting times (activated partial thromboplastin time (APTT) and prothrombin time (PT)), and complement activation on C3a and C5a levels. The results indicated that the blood compatibility of PES matrix was improved due to the biologically inspired membrane design with a heparin-like interface by introducing functional sulfonic acid and carboxylic acid groups. Furthermore, cell morphology observation and cell culture assays demonstrated that the modified membranes showed better performance in bio-artificial liver related cell proliferation than the pristine PES membrane. In general, the intriguing PES/CPES/SPES membranes, especially the phase-inversion one, showed improved blood and cell compatibility, which might have great potential application in the blood purification field.

Surface-engineered nanogel assemblies with integrated blood compatibility, cell proliferation and antibacterial property: towards multifunctional biomedical membranes

In this study, novel 3D multifunctional nanolayers are fabricated on biomedical membrane surfaces via layer-by-layer (LBL) self-assembly of nanogels and heparin-like polymers. To integrate long-term antibacterial activity, Ag nanoparticles embedded in nanogels were first prepared. Then, the Ag nanogels were assembled onto membrane surfaces by electrostatic interaction. To obtain a heparin-mimicking surface, the as-prepared nanogel-coated membranes were further assembled with heparin-like polymers by two different processes. The results indicated that the obtained nanogel and heparin-mimicking polymer assembled membranes exhibited 3D surface morphologies. Systematical blood compatibility and antithrombotic evaluations revealed that the functionalized membranes showed increased hydrophilicity, decreased protein adsorption, and prolonged clotting times and greatly suppressed platelet adhesion compared to pristine membrane. The cell culture observations demonstrated that the pristine, nanogel-assembled, and heparin-mimicking membranes showed different performances in terms of endothelial cell proliferation and adhesion morphology. The results of the antibacterial study indicated that the functionalized membranes exhibited significant inhibition capability for Escherichia coli and Staphylococcus aureus. In general, the surface coassembly of nanogels and heparin-mimicking polymers produced functionalized membranes with integrated blood compatibility, cell proliferation and antibacterial properties for multiple applications, which may advance the fabrication of biomedical devices by surface assembly of functional nanogels.