Zhen-Qiang Shi

Graphene oxide based heparin-mimicking and hemocompatible polymeric hydrogels for versatile biomedical applications

Studies on the design of heparin and heparin-mimicking polymer based hydrogels are of tremendous interest and are fuelled by diverse emerging biomedical applications, such as antithrombogenic materials, growth factor carriers, and scaffolds for tissue engineering and regeneration medicine. In this study, inspired by the recent developments of heparin-based hydrogels, graphene oxide (GO) based heparin-mimicking hydrogels with hemocompatibility and versatile properties were prepared via free radical copolymerization, and poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 2-hydroxyethyl methacrylate (HEMA) hydrogels were used as the control samples. The GO based heparin-mimicking polymeric hydrogels exhibited interconnected structures with thin pore walls and high porosity. Because of the increased ionization and electrostatic repulsion of sodium styrene sulfonate (SSNa) segments, the swelling ratios of the SSNa added hydrogels were dramatically increased; after incorporating flexible GO nanosheets, as the 3D skeleton of the hydrogels, the swelling ability was further increased. In addition, the GO based heparin-mimicking hydrogels showed superior red blood cell compatibility, anti-platelet adhesion ability and anticoagulant ability. Furthermore, drug release data indicated that the GO based heparin-mimicking hydrogels had high drug loading ability and prolonged drug releasing ability; the antibacterial tests showed coincident results with large inhibition zones and long effective periods. Due to the integration of blood compatibility, drug loading and releasing abilities, as well as an excellent ability for the removal of toxic molecules, the GO based heparin-mimicking hydrogels can be used for versatile biomedical applications.

Host–Guest Self-Assembly Toward Reversible Thermoresponsive Switching for Bacteria Killing and Detachment

A facile method to construct reversible thermoresponsive switching for bacteria killing and detachment was currently developed by host-guest self-assembly of β-cyclodextrin (β-CD) and adamantane (Ad). Ad-terminated poly(N-isopropylacrylamide) (Ad-PNIPAM) and Ad-terminated poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (Ad-PMT) were synthesized via atom transfer radical polymerization, and then assembled onto the surface of β-CD grafted silicon wafer (SW-CD) by simply immersing SW-CD into a mixed solution of Ad-PNIPAM and Ad-PMT, thus forming a thermoresponsive surface (SW-PNIPAM/PMT). Atomic force microscopy (AFM), X-ray photoelectron spectrometry (XPS), and water contact angle (WCA) analysis were used to characterize the surface of SW-PNIPAM/PMT. The thermoresponsive bacteria killing and detachment switch of the SW-PNIPAM/PMT was investigated against Staphyloccocus aureus. The microbiological experiments confirmed the efficient bacteria killing and detachment switch across the lower critical solution temperature (LCST) of PNIPAM. Above the LCST, the Ad-PNIPAM chains on the SW-PNIPAM/PMT surface were collapsed to expose Ad-PMT chains, and then the exposed Ad-PMT would kill the attached bacteria. While below the LCST, the previously collapsed Ad-PNIPAM chains became more hydrophilic and swelled to cover the Ad-PMT chains, leading to the detachment of bacterial debris. Besides, the proposed method to fabricate stimuli-responsive surfaces with reversible switches for bacteria killing and detachment is facile and efficient, which creates a new route to extend the application of such smart surfaces in the fields requiring long-term antimicrobial treatment.

Engineering polyethersulfone hollow fiber membrane with improved blood compatibility and antibacterial property

AbstractHollow fiber membranes with satisfied blood compatibility and antibacterial property are desired in blood purification. Herein, a series of heparin-like copolymers of poly(methyl methacrylate-vinyl pyrrolidone -sodium styrene sulfonate-sodium acrylate) (poly(MMA-VP-SSNa-SA)) were synthesized by free radical solution polymerization. The mixture was directly blended with polyethersulfone (PES) solution to prepare hollow fiber membranes. The membranes were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Blood compatibility of the hollow fiber membranes was evaluated via protein adsorption, platelet adhesion, clotting time, and hemolysis assay. Besides, Ag nanoparticles were immobilized onto the hollow fiber membranes efficiently by a simple and green method, and the antibacterial property and blood compatibility of the Ag-loaded membranes were then investigated. The results indicated that the approach towards blood compatible and antibacterial hollow fiber membrane is efficient and flexible for the modification for membrane materials. Graphical abstractᅟ

Robust, highly elastic and bioactive heparin-mimetic hydrogels

In this study, we report the rapid synthesis of robust, highly elastic and bioactive heparin-mimetic hydrogels by combining free radical polymerization with doped graphene oxide (GO) as the micro-crosslinker. In the hydrogel system, GO is covalently connected or bonded to the heparin-mimetic polymer networks since the initiated macromolecular radicals can attach to the double bonds of GO. As a result, the GO doped heparin-mimetic hydrogels reveal highly interpenetrating networks with increased small pores, thinner pore walls, and a narrow pore size distribution compared to pristine heparin-mimetic hydrogels. Meanwhile, the GO doped heparin-mimetic hydrogels can also sustain cyclic compressions with extremely high strain due to the reinforced mechanical strength and elastic properties. Furthermore, all of the heparin-mimetic hydrogels show excellent endothelial cell compatibility, and doping with GO can further improve the cell viability and promote the generation of actin filaments and extracellular matrix. Moreover, the heparin-mimetic hydrogels also show a high drug loading ability and a persistent releasing ability, thus exhibiting sustained antitumor cell activity; doping with GO can help achieve more slow doxorubicin (DOX) release and better anti-cancer efficiency than the pristine hydrogel. Combined with the excellent properties mentioned above, we believe that the synthesized GO doped heparin-mimetic hydrogels will have great potential for application in various biomedical fields, such as tissue engineering and implantable drug delivery systems.

A Water‐Processable and Bioactive Multivalent Graphene Nanoink for Highly Flexible Bioelectronic Films and Nanofibers

The capabilities of conductive nanomaterials to be produced in liquid form with well-defined chemical, physical, and biological properties are highly important for the construction of next-generation flexible bioelectronic devices. Although functional graphene nanomaterials can serve as attractive liquid nanoink platforms for the fabrication of bioelectronics, scalable synthesis of graphene nanoink with an integration of high colloidal stability, water processability, electrochemical activity, and especially bioactivity remains a major challenge. Here, a facile and scalable synthesis of supramolecular-functionalized multivalent graphene nanoink (mGN-ink) via [2+1] nitrene cycloaddition is reported. The mGN-ink unambiguously displays a well-defined and flat 2D morphology and shows good water processability and bioactivity. The uniquely chemical, physical, and biological properties of mGN-ink endow the constructed bioelectronic films and nanofibers with high flexibility and durability, suitable conductivity and electrochemical activity, and most importantly, good cellular compatibility and a highly efficient control of stem-cell spreading and orientation. Overall, for the first time, a water-processable and bioactive mGN-ink is developed for the design of flexible and electrochemically active bioelectronic composites and devices, which not only presents manifold possibilities for electronic-cellular applications but also establishes a new pathway for adapting macroscopic usages of graphene nanomaterials in bionic, biomedical, electronic, and even energy fields.

Multi-responsive, tough and reversible hydrogels with tunable swelling property

A novel family of multi-responsive, tough, and reversible hydrogels were prepared by the combination of dipole-dipole interaction, hydrogen bonding interaction and slightly chemical cross-linking, using monomers of acrylonitrile, sodium allylsulfonate and itaconic acid. Reversible gel-sol transition was achieved by the flexible conversion of the dipole-dipole interactions between acrylonitrile-acrylonitrile and acrylonitrile-sodium thiocyanate, and the hydrogels could freely form desired shapes. The dipole-dipole and hydrogen bonding interactions improved the mechanical strength of the hydrogels with a compressive stress of 2.38MPa. Meanwhile, the hydrogels sustained cyclic compressive tests with 60% strain, and exhibited excellent elastic property. The hydrogels were sensitive to pH and ionic strength, and could keep their perfect spherical structures without any obvious cracks even after immersing in strong ionic strength (or pH) solution for several reversible cycles. Furthermore, the hydrogels were recycled for environmental pollution remediation, and showed great potential to be applied in water treatments and other related fields.

Inflammation-responsive self-regulated drug release from ultrathin hydrogel coating

Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin. A porous structure of the attached hydrogel layer was observed by scanning electron microscopy, and the presence of drug molecules in the hydrogel layer was confirmed by X-ray photoelectron spectroscopy and UV-vis absorption spectra. The drug release could be triggered under the mimicking inflammation environment, and the release rate was responsive to the inflammation degree. In addition, after attaching the hydrogel coating, the substrate showed low cytotoxicity, and high promotion for cell adhesion and proliferation. The excellent hemocompatibility of the hydrogel coating was also demonstrated by prolonged clotting time and suppressed platelet adhesion. This work suggests that the inflammation-responsive indometacin conjugated hydrogel coating has great potential to be used for prophylaxis HO.

Highly swellable and biocompatible graphene/heparin-analogue hydrogels for implantable drug and protein delivery

Research on the design of heparin-analogue hydrogels is of tremendous importance and fuelled by diverse emerging biomedical applications, such as cancer inhibition, treatments of genetic diseases, growth factor carriers, and scaffolds for regeneration medicine, due to their specific biological and biocompatible properties. In this study, by taking inspiration from recent advancements of graphene nanomaterials and heparin-analogue polymers, we designed a kind of highly swellable, elastic, hemo- and cyto-compatible graphene oxide (GO) hybridized heparin-analogue hydrogels for potential drug and protein delivery. The fabricated GO/heparin-analogue hydrogels (GHHs) exhibited an inner-interpenetrated porous structure and robust mechanical properties compared to the GO absent heparin-analogue hydrogel (HH). Notably, the GHHs showed excellent results for in vitro biocompatibility, such as red blood cell compatibility, anti-platelet adhesion and activation, low inflammation potential, high endothelial cell compatibility. Furthermore, after adding GO, the hydrogels showed improved loading and persistent release abilities of doxorubicin hydrochloride (DOX); the GHHs also demonstrated their potential for efficient protein loading and long-term releasing. Due to the integration of elastic mechanical properties, hemo- and cyto-compatibility, as well as drug and protein delivery abilities, the GO hybridized heparin-analogue hydrogels open up a new potential protocol for implantable drug and protein delivery therapies, and bioactive scaffolds for tissue regeneration.