The effects of ECMO on neurological function recovery of critical patients: A double-edged sword.

Extracorporeal membrane oxygenation (ECMO) played an important role in the treatment of patients with critical care such as cardiac arrest (CA) and acute respiratory distress syndrome. ECMO is gradually showing its advantages in terms of speed and effectiveness of circulatory support, as it provides adequate cerebral blood flow (CBF) to the patient and ensures the perfusion of organs. ECMO enhances patient survival and improves their neurological prognosis. However, ECMO-related brain complications are also important because of the high risk of death and the associated poor outcomes. We summarized the reported complications related to ECMO for patients with CA, such as north-south syndrome, hypoxic-ischemic brain injury, cerebral ischemia-reperfusion injury, impaired intracranial vascular autoregulation, embolic stroke, intracranial hemorrhage, and brain death. The exact mechanism of ECMO on the role of brain function is unclear. Here we review the pathophysiological mechanisms associated with ECMO in the protection of neurologic function in recent years, as well as the ECMO-related complications in brain and the means to improve it, to provide ideas for the treatment of brain function protection in CA patients.

An Antibacterial and Antiadhesion In Situ Forming Hydrogel with Sol-Spray System for Noncompressible Hemostasis.

Noncompressible hemorrhage is a major cause of posttrauma death and occupies the leading position among potentially preventable trauma-associated deaths. Recently, multiple studies have shown that strongly adhesive materials can serve as hemostatic materials for noncompressible hemorrhage. However, the risk of severe tissue adhesion limits the use of adhesive hydrogels as hemostatic materials. Here, we report a promising material system comprising an injectable sol and liquid spray as a potential solution. Injectable sol is mainly composed of gelatin (GEL) and sodium alginate (SA), which possess hemostasis and adhesive properties. The liquid spray component, a mixture of tannic acid (TA) and calcium chloride (CaCl2), rapidly forms an antibacterial, antiadhesive and smooth film structure upon contact with the sol. In vitro and in vivo experiments demonstrated the bioabsorbable, biocompatible, antibacterial, and antiadhesion properties of the in situ forming hydrogel with a sol-spray system. Importantly, the addition of tranexamic acid (TXA) enhanced hemostatic performance in noncompressible areas and in deep wound hemorrhage. Our study offers a new multifunctional hydrogel system to achieve noncompressible hemostasis.

Sea Cucumber-Inspired Autolytic Hydrogels Exhibiting Tunable High Mechanical Performances, Repairability, and Reusability.

Inspired by stimuli-responsive remarkable changes in consistency (hardening, softening, autolysis) of sea cucumbers, we synthesized a supramolecular polymer(SP) hydrogel directly by photoinitiated aqueous polymerization of N-acryloyl 2-glycine monomer bearing one amide and one carboxyl group on the side chain. The SP hydrogels doped with Ca(2+) demonstrated excellent mechanical properties-high tensile strength (∼1.3 MPa), large stretchability (up to 2300%), high compressive strength (∼10.8 MPa), and good toughness (∼1000 J m(-2)) due to cooperative hydrogen bonding interactions from amide and carboxyl together with Ca(2+) cross-linking. Responding to the change in pH and Ca(2+) concentration, the hydrogels could modulate their network stability and mechanical properties: at pH3.0 and higher Ca(2+) content, the hydrogel formed low swelling network which was stiff and stable; in alkaline or neutral buffer with lower content of or without Ca(2+), the hydrogel formed a highly swollen transient network, which was soft and eventually autolyzed. The reversible multiple noncovalent bonds enabled the hydrogels to achieve thermoplasticity, self-healability, and reusability. Notably, distinct formulations of hydrogels could be welded together under heating to form a gradient hydrogel. In vitro cytotoxicity assay and subcutaneous implantation indicated that the SP hydrogels were biocompatible and autolytic in vivo. The SP hydrogels may find applications as temporary biodevices for intestinal drug delivery or for injectable filling in assisting suturing small vessels.

High Strength Multifunctional Multiwalled Hydrogel Tubes: Ion-Triggered Shape Memory, Antibacterial, and Anti-inflammatory Efficacies.

In this study, ion-responsive hydrogen bonding strengthened hydrogels (termed as PVV) were synthesized by one-pot copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), 1-vinylimidazole (VI), and polyethylene glycol diacrylate. The diaminotriazine-diaminotriazine (DAT-DAT) H-bonding interaction and copolymerization of VI contributed to a notable increase in comprehensive performances including tensile/compressive strength, elasticity, modulus, and fracture energy. In addition, introducing mM levels of zinc ions could further increase the mechanical properties of PVV hydrogels and fix a variety of temporary shapes due to the strong coordination of zinc with imidazole. The release of zinc ions from the hydrogel contributed to an antibacterial effect, without compromising the shape memory effect. Remarkably, a multiwalled hydrogel tube (MWHT) fixed with Zn(2+) demonstrated much higher flexural strengths and a more sustainable release of zinc ions than the solid hydrogel cylinder (SHC). A Zn(2+)-fixed MWHT was implanted subcutaneously in rats, and it was found that the Zn(2+)-fixed MWHT exhibited anti-inflammatory and wound healing efficacies. The reported high strength hydrogel with integrated functions holds potential as a tissue engineering scaffold.

Co-delivery of doxorubicin and tumor-suppressing p53 gene using a POSS-based star-shaped polymer for cancer therapy.

In this work, a star-shaped polymer consisting of a cationic poly[2-(dimethylamino) ethyl methacrylate] (PDMAEMA) shell and a zwitterionic poly[N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide] (PMPD) corona was grafted from a polyhedral oligomeric silsesquioxanes (POSS)-based initiator via atomic transfer radical polymerization (ATRP). The reported star-shaped polymer could form stable micelles in aqueous solutions even in the presence of serum. In addition, anti-cancer drug doxorubicin and tumor-suppressing p53 gene were loaded in the process of micelle formation. The formed polyplex was biocompatible and highly efficient for both drug and gene delivery. Furthermore, the polyplex was able to cause a high apoptotic rate of tumor cells both in vitro and in vivo. This combination delivery strategy offers a promising method for cancer therapy and can be used for further clinical applications.

Enhanced Therapeutic siRNA to Tumor Cells by a pH-Sensitive Agmatine-Chitosan Bioconjugate.

Charge-conversional naturally occurring chitosan-agmatine bioconjugates are prepared by dimethylmaleic anhydride (DMA) modification and the nucleophilic reaction between tosyl of tosylated chitosan and primary amine of agmatine. These bioconjugates (CS-DM-Agm) are shown to condense siRNA into nanocomplexes, which are stable in the presence of serum at physical pH values. Furthermore, the surface charge of complexes can tune from negative to positive while pH is changed to weak acid tumor micromilieu, thus facilitating the target cancer cell internalization in resisting serum adsorption. More importantly, this smart biogenic system shows remarkable gene silencing efficiency and a high apoptotic rate of tumor cells both in vitro and in vivo, indicating its great potential for cancer therapy.

Correction: Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling.

Correction for 'Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling' by Wei Wang et al., J. Mater. Chem. B, 2014, 2, 46-48.

Hydrogen bonded and ionically crosslinked high strength hydrogels exhibiting Ca2+-triggered shape memory properties and volume shrinkage for cell detachment.

A hydrogen bonded and calcium ion crosslinked hydrogel, termed PVDT-PAA, was synthesized by one-step photo-polymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), acrylic acid (AA), and polyethylene glycol diacrylate (PEGDA, Mn = 4000). Combined physical crosslinking from inter-diaminotriazine and coordination of Ca2+ with carboxyls contributed to a significant enhancement in the mechanical properties of the PVDT-PAA hydrogels. Furthermore, reversible Ca2+ crosslinking imparted shape memory properties to the hydrogel allowing it to firmly memorize multiform shapes and return to its initial state in response to Ca2+. Interestingly, PVDT-PAA hydrogels with weaker H-bonding interactions demonstrated a sharp volume change phenomenon induced by Ca2+. This volume change could be utilized to trigger unharmful cell detachment from the hydrogel surface, which was thought to be due to Ca2+-induced marked variation in mechanotransduction between the cells and the substrate interface. This H-bonding and ionic crosslinking strategy opens up a new opportunity for designing and constructing multifunctional high strength hydrogels for biomedical applications.

Polycation-b-polyzwitterion copolymer grafted luminescent carbon dots as a multifunctional platform for serum-resistant gene delivery and bioimaging.

Nanomaterials that integrate functions of imaging and gene delivery have been of great interest due to their potential use in simultaneous diagnosis and therapy. Herein, polycation-b-polysulfobetaine block copolymer, poly[2-(dimethylamino) ethyl methacrylate]-b-poly[N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide] (PDMAEMA-b-PMPDSAH) grafted luminescent carbon dots (CDs) were prepared via surface-initiated atom transfer radical polymerization (ATRP) and investigated as a multifunctional gene delivery system (denoted as CD-PDMA-PMPD) in which the CD cores acted as good multicolor cell imaging probes, the cationic PDMAEMA acted as a DNA condensing agent, and the outer shell of zwitterionic PMPDSAH block protected the vector against nonspecific interactions with serum components. As revealed by the fluorescent spectrum study, the photoluminescent attributes, especially the tunable emission property, were well inherited from the parent CDs. The CD-PDMA-PMPD could condense plasmid DNA into nanospheres with sizes of approximate 50 nm at a proper complex ratio, posing little cytotoxicity at higher ratios. It was shown that the hybrid vector exhibited significantly suppressed BSA protein adsorption and superior hemocompatibility compared to those of the widely used PEI25k. In the in vitro transfection assay, an increased serum concentration from 10 to 50% caused a dramatic drop in PEI25k transfection performance, whereas the transfection efficiency of CD-PDMA-PMPD was well maintained; CD-PDMA80-PMPD40 showed 13 and 28 times higher transfection efficiencies than PEI25k at 30 and 50% serum concentration, respectively. Intriguingly, the carbon dots in the transfected cells displayed excitation-dependent fluorescent emissions, portending that this polycation-polyzwitterion modified CD will be a promising theranostic vector with excellent stealth performance.

High-strength photoresponsive hydrogels enable surface-mediated gene delivery and light-induced reversible cell adhesion/detachment.

In the present study, high-strength photoresponsive hydrogels were prepared by the photoinitiated copolymerization of acrylamide (AAm, hydrophilic hydrogen bonding monomer), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT, hydrophobic hydrogen bonding monomer), and spiropyran-containing monomer (SPAA) in the presence of cross-linker poly(ethylene glycol) diacrylate (PEG575DA, Mn = 575). The double hydrogen bondings from AAm-AAm and diaminotriazine-diaminotriazine contributed to the considerable enhancement in tensile and compressive properties of the hydrogels, which showed an excellent ability to resist a variety of external forces. Fifteen minutes of UV (365 nm) irradiation led to the detachment of adhered cells due to the increased surface hydrophilicity caused by the isomerization of spiropyran moieties. Furthermore, repeated attachment/detachment of cells was realized by the alternate illumination of visible and UV light. Reverse gene transfection was carried out successfully by anchoring the PVDT/pDNA complex nanoparticles on the gel surface through hydrogen bonding between diaminotriazine motifs prior to cell seeding. Importantly, fibronectin (FN) modification combined with supplementing PVDT/pDNA complex nanoparticles after the first cycle of reverse gene transfection, so-called sandwich gene transfection, further increased the gene transfection level. A short time of UV light exposure could result in the nonharmful detachment of gene-modified cells from the gel surface. This high-strength photosensitive hydrogel holds potential as a reusable soft-wet platform for cell harvesting as well as gene transfection operation at higher efficiency.

Redox-triggered self-rolling robust hydrogel tubes for cell encapsulation.

In this study, mechanically strong hydrogels are synthesized by photopolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine, poly(ethylene glycol) methacrylate, and disulfide-containing cross-linker, N'N-bis(acryloyl)cystamine. The bilayer hydrogel with distinct cross-linking density is shown to self-roll into a 3D tube, which could still be well reinforced by hydrogen bondings, upon exposing reductants such as 1,4-dithio-DL-threitol (DTT) or L-glutathione (GSH), because the redox-induced cleavage of disulfide bonds results in the imbalanced internal shrinking stress between two layers. At an intracellular level of GSH, model L929 cells-seeded bilayer gel sheet could curl up into a 3D tubular scaffold where the cells maintained good viability.

Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling.

Water-soluble phosphorus-containing carbon dots (PCDs) with strong green fluorescence were synthesized through a facile one-step microwave assisted approach using phosphorus-rich phytic acid as a carbon source. Owing to their strong green fluorescence and low cytotoxicity, the PCDs are promising as bio-imaging agents.

UV light-triggered unpacking of DNA to enhance gene transfection of azobenzene-containing polycations.

This study demonstrates a strategy to enhance gene delivery via photoregulated gene unpacking from its vector. Photoresponsive polycationic vectors composed of a middle azobenzene moiety and two terminal blocks of poly[2-(dimethylamino)ethyl methacrylate], termed as Azo-PDMAEMA, are synthesized using a difunctional azobenzene-based initiator via atomic transfer radiator polymerization (ATRP). The Azo-PDMAEMA exhibits trans to cis isomerization under alternate Vis-UV irradiation, and is capable of condensing plasmid DNA into nanocomplexes. Hydrophobic azobenzene groups in the cationic polymers are shown to enhance the interaction of complexes with the cell membrane, thus improving cell uptake and transfection efficiency. Increased gene expression in COS-7 cells, HepG-2 cells and CHO-K1 cells is achieved after UV irradiation due to UV-triggered intracellular gene unpacking. Time-resolved fluorescence assays further indicate that the trans to cis photoisomerization of Azo-PDMAEMA induces less compacted complexes, contributing to more exposure of genes for transcription.

Combining magnetic field/temperature dual stimuli to significantly enhance gene transfection of nonviral vectors.

Monodisperse magnetic nanoparticles (MNPs) were prepared through an organic phase process, and the obtained MNPs were capped with poly[2-(2-methoxyethoxy)ethyl methacrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] synthesized by surface-initiated atom transfer radical polymerization (ATRP). The MNPs-polymer brushes exhibited both superparamagnetic and thermoresponsive behaviors, and could condense plasmid DNA into nanocomplexes with a size of 100-120 nm at appropriate complexing ratios. Enhanced gene expression in COS-7 cells and HepG-2 cells was achieved under a magnetic field and variable temperature conditions due to magnetic force-facilitated internalization of nanocomplexes, and temporary cooling-triggered intracellular gene unpacking. Amazingly, combining magnetic field and temperature dual stimuli contributed to a 50-100- and 25-45-fold increase of the transfection efficiency in HepG-2 cells compared to conventional protocol and PEI25k, respectively.

Monoclonal antibodies against NS3 and NS5 proteins of Japanese encephalitis virus.

Non-structural proteins NS3 and NS5 of Japanese encephalitis virus (JEV) were expressed in Escherichia coli and purified by dialysis. Two monoclonal antibodies (MAbs) named 1H7 and 2D4 against NS3 protein and three MAbs named 3C4, 3H7, and 3F10 against NS5 protein were generated by fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from NS3 or NS5 protein immunized mice. Then activity of MAbs was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunofluorescent assays (IFA). Our results demonstrated that all the MAbs showed high specificity and sensitivity in IFA at 1:100 dilution and in Western blot analysis at 1:500 dilution, which indicated that these MAbs against NS3 and NS5 proteins of JEV may be used as valuable tools for analysis of the protein functions and pathogenesis of JEV.