Shengqiang Nie

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.

Biocompatibility of modified polyethersulfone membranes by blending an amphiphilic triblock co-polymer of poly(vinyl pyrrolidone)-b-poly(methyl methacrylate)-b-poly(vinyl pyrrolidone).

An amphiphilic triblock co-polymer of poly(vinyl pyrrolidone)-b-poly(methyl methacrylate)-b-poly(vinyl pyrrolidone) (PVP-b-PMMA-b-PVP) was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The block co-polymer can be directly blended with polyethersulfone (PES) using dimethylacetamide (DMAC) as the solvent to prepare flat sheet and hollow fiber membranes using a liquid-liquid phase separation technique. The PVP block formed a brush on the surface of the blended membrane, while the PMMA block mingled with the PES macromolecules, which endowed the membrane with permanent hydrophilicity. After adding the as-prepared block co-polymer the modified membranes showed lower protein (bovine serum albumin) adsorption, suppressed platelet adhesion, and a prolonged blood coagulation time, and thereby the blood compatibility was improved. Furthermore, the modified PES membranes showed good cytocompatibility, ultrafiltration and protein anti-fouling properties. These results suggest that surface modification of PES membranes by blending with the amphiphilic triblock co-polymer PVP-b-PMMA-b-PVP allows practical application of these membranes with good biocompatibility in the field of blood purification, such as hemodialysis and bioartificial liver support.

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.

Improved blood compatibility of polyethersulfone membrane with a hydrophilic and anionic surface

In this study, a novel triblock copolymer of poly (styrene-co-acrylic acid)-b-poly (vinyl pyrrolidone)-b-poly(styrene-co-acrylic acid) (P(St-co-AA)-b-PVP-b-P(St-co-AA)) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and used for the modification of blood contacting surface of polyethersulfone (PES) membrane to improve blood compatibility. The synthesized block copolymer can be directly blended with PES to prepare PES membranes by a liquid-liquid phase separation technique. The compositions and structure of the PES membranes are characterized by thermogravimetric analysis (TGA), ATR-FTIR, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM); the surface charge density of the modified PES membrane was measured by Zeta-potential; the blood compatibility of the PES membranes was assessed by detecting bovine serum albumin (BSA) and bovine serum fibrinogen (BFG) adsorption, platelet adhesion, activated partial thromboplastin time (APTT), platelet activation, and thrombin-antithrombin III (TAT) generation. The results indicated that the blood compatibility of the modified PES membrane was improved due to the membrane surface modification by blending the amphiphilic block copolymer and the surface segregation of the block copolymer.

Heparin‐Like Macromolecules for the Modification of Anticoagulant Biomaterials

A heparin-like structured macromolecule (HLSM) is synthesized by RAFT polymerization using carboxyl-terminated trithiocarbonate as the RAFT agent. The HLSM can be directly blended with PES in DMAC to prepare flat-sheet membrane by means of a liquid-liquid phase separation technique. The synthesized polymeric material retard blood clotting and the modified membrane exhibits good anticoagulant ability due to the existence of the important functional groups SO(3) H, COOH and OH. The anionic groups on the membrane surface may bind coagulation factors and thus improve anticoagulant ability. The results indicate that the HLSM has potential to improve the anticoagulant properties of biomaterials and to be applied in blood purification including hemodialysis and bioartificial liver supports.

Direct synthesis of heparin-like poly(ether sulfone) polymer and its blood compatibility.

In this study, heparin-like poly(ethersulfone) (HLPES) was synthesized by a combination of polycondensation and post-carboxylation methods, and was characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance hydrogen spectrum and gel permeation chromatography. Owing to the similar backbone structure, the synthesized HLPES could be directly blended with pristine PES at any ratios to prepare PES/HLPES membranes. After the introduction of HLPES, the microscopic structure of the modified PES membranes was changed, while the hydrophilicity was significantly enhanced. Bovine serum albumin and bovine serum fibrinogen adsorption, activated partial thromboplastin time, thromb time and platelet adhesion for the modified PES membranes were investigated. The results indicated that the blood compatibility of the PES/HLPES membranes was significantly improved compared with that of pristine PES membrane. For the PES/HLPES membranes, obvious decreases in platelet activation on PF-4 level, in complement activation on C3a and C5a levels, and in leukocytes activation on CD11b levels were observed compared with those for the pristine PES membrane. The improved blood compatibility of the PES/HLPES membrane might due to the existence of the hydrophilic groups (-SO3Na, -COONa). Furthermore, the modified PES membranes showed good cytocompatibility. Hepatocytes cultured on the PES/HLPES membranes presented improved growth in terms of SEM observation, MTT assay and confocal laser scanning microscope observation compared with those on the pristine PES membrane. These results indicate that the PES/HLPES membranes present great potential in blood-contact fields such as hemodialysis and bio-artificial liver supports.

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.

Layer by layer assembly of sulfonic poly(ether sulfone) as heparin-mimicking coatings: scalable fabrication of super-hemocompatible and antibacterial membranes

In this study, to approach the scalable fabrication of super-hemocompatible and antibacterial membranes, surface engineered 3D heparin-mimicking coatings were designed by layer by layer (LBL) assembly of water-soluble heparin-mimicking polymer (WHP) and quaternized chitosan (QC). The low cost and scalable WHP was synthesized by a combination of polycondensation and post-carboxylation method, and the antibacterial QC was prepared by a two-step quaternization reaction. Then, the as-prepared negatively charged WHP and positively charged QC were used to conduct the LBL assembly on the widely used poly(ether sulfone) (PES) membrane surface to prepare heparin-mimicking modified membrane. The results indicated that the assembled heparin-mimicking coating nanofilms exhibited 3D porous morphology. The systematic blood compatibility and antithrombotic evaluation revealed that the functionalized membrane owned prolonged clotting times and greatly suppressed platelet adhesion and activation; further contacting activation detection (TAT and PF-4) and complement activation (C3a and C5a) experiments indicated that the heparin-mimicking membranes had lower blood activation compared to the pristine membrane. The cell observations demonstrated that the surface assembled heparin-mimicking nanofilms showed superior performances in endothelial cells adhesion and growth than the pure PES membrane. The results of the antibacterial study indicated that the QC contained coating exhibited significant inhibition ability for both Escherichia coli and Staphlococcus aureus. In general, the LBL assembled heparin-mimicking coatings conferred the functionalized PES membranes with integrated blood compatibility, cytocompatibility and antibacterial property for multi-applications, which may forward the fabrication and application of heparin-mimicking biomedical devices.

Blood activation and compatibility on single-molecular-layer biointerfaces

Research on the interactions between living systems and materials is fuelled by diverse biomedical needs, for example, drug encapsulation and stimulated release, stem cell proliferation and differentiation, cell and tissue cultures, as well as artificial organs. Specific single-molecular-layer biointerface design is one of the most important processes to reveal the interactions or biological responses between synthetic biomaterials and living systems. However, until now, there is limited literature on comprehensively revealing biomaterials induced blood component activation and hemocompatibility based on the single-molecular-layer interface approach. In this study, the effects of different groups on blood compatibility are presented using single-molecular-layer silicon (Si) interfaces. Typical hydrophilic groups (hydroxyl, carboxyl, sulfonic, and amino groups) and hydrophobic groups (alkyl, benzene, and fluorinated chains) are introduced onto single-molecular-layer Si interfaces and confirmed by atomic force microscopy, X-ray photoelectron spectroscopy, and water contact angle. The blood activation and compatibility for the prepared biointerfaces are systematically investigated by protein adsorption, clotting time, Factor XII detection, platelet adhesion, contacting activation, and complement activation experiments. The results indicate that the blood activation and hemocompatibility for the biointerfaces are complex and highly related to the chemical groups and hydrophilicity of the surfaces. Our results further indicate the vital importance of carefully designed biointerfaces for specific biomedical applications. The carboxyl group, sulfonic group, and hydroxyl group may be more suitable for the interface designs of antifouling materials. The results also reveal that the sulfonic group and fluorinated surface possess great potential for applications of blood contacting devices due to their low contacting blood activation.

Blood compatibility of polyethersulfone membrane by blending a sulfated derivative of chitosan

In this study, a novel sulfated derivative of chitosan, which could be dissolved in many common organic solvents, is conveniently synthesized for the modification of polyethersulfone (PES) membrane. Elemental analysis, FTIR, (1)H NMR and X-ray diffraction diagrams (XRD) are used to demonstrate the introduction of functional groups. Owing to the solubility in organic solvents, the sulfated derivative of chitosan could be directly blended with PES in organic solvent to prepare membrane by means of a liquid-liquid phase separation technique. The modified membrane showed lower protein (bovine serum albumin (BSA) and bovine serum fibrinogen (BFG)) adsorption and suppressed platelet adhesion. Moreover, the activated partial thromboplastin time (APTT) for the modified membrane was enhanced as high as 60% compared to pure PES membrane. The lower protein adsorption, suppressed platelet adhesion and increased APTT confirmed that the blood compatibility of the modified PES membrane by the sulfated derivative of chitosan was significantly improved.