Simultaneous Rosiglitazone Release and Low-Density Lipoprotein Removal by Chondroitin Sodium Sulfate/Cyclodextrin/Poly(acrylic acid) Composite Adsorbents for Atherosclerosis Therapy.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

Porous Microspheres as Pathogen Traps for Sepsis Therapy: Capturing Active Pathogens and Alleviating Inflammatory Reactions.

Sepsis is a systemic inflammatory response syndrome caused by pathogen infection, while the current antibiotics mainly utilized in clinical practice to combat infection result in the release of pathogen-associated molecular patterns (PAMPs) in the body. Herein, we provide an innovative strategy for controlling sepsis, namely, capturing active pathogens by means of extracorporeal blood purification. Carbon nanotubes (CNTs) were modified with dimethyldiallylammonium chloride (DDA) through γ-ray irradiation-induced graft polymerization to confer a positive charge. Then, CNT-DDAs are blended with polyurethane (PU) to prepare porous microspheres using the electro-spraying method. The obtained microspheres with a pore diameter of 2 µm served as pathogen traps and are termed as PU-CNT-DDA microspheres. Even at a high flow rate of 50 mL·min-1, the capture efficiencies of the PU-CNT-DDAs for Escherichia coli and Staphylococcus aureus remained 94.7% and 98.8%, respectively. This approach circumvents pathogen lysis and mortality, significantly curtails the release of PAMPs, and hampers the production of pro-inflammatory cytokines. Therefore, hemoperfusion using porous PU-CNT-DDAs as pathogen traps to capture active pathogens and alleviate inflammation opens a new route for sepsis therapy.

Self-anticoagulant sponge for whole blood auto-transfusion and its mechanism of coagulation factor inactivation.

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

Ultraporous Polyquaternium-Carboxylated Chitosan Composite Hydrogel Spheres with Anticoagulant, Antibacterial, and Rapid Endotoxin Removal Profiles for Sepsis Treatment.

Hemoperfusion is an important method to remove endotoxins and save the lives of patients with sepsis. However, the current adsorbents for hemoperfusion have disadvantages of insufficient endotoxin adsorption capacity, poor blood compatibility, and so on. Herein, we proposed a novel emulsion templating (ET) method to prepare ultraporous and double-network carboxylated chitosan (CCS)-poly(diallyl dimethylammonium chloride) (PDDA) hydrogel spheres (ET-CCSPD), bearing both negative and positive charges. CCS was introduced to balance the strong positive charges of PDDA to improve hemocompatibility, and emulsion templates endowed the adsorbent with an ultraporous structure for enhanced adsorption efficacy. The ET-CCSPDs neither damaged blood cells nor activated complement responses. In addition, the activated partial thromboplastin time (APTT) was prolonged to 8.5 times, which was beneficial for reducing the injection of anticoagulant in patients. The ET-CCSPDs had excellent scavenging performance against bacteria and endotoxin, with removal ratios of 96.7% for E. coli and 99.8% for S. aureus, respectively, and the static removal ratio of endotoxin in plasma was as high as 99.1% (C0 = 5.50 EU/mL, critical illness level). An adsorption cartridge filled with the ET-CCSPDs could remove 84.7% of endotoxin within 1 h (C0 = 100 EU/mL in PBS). Interestingly, the ET-CCSPDs had a good inhibitory effect on the cytokines produced by endotoxin-mediated septic blood. By developing the ET method to prepare ultraporous and double-network adsorbents, the problems of low adsorption efficiency and poor blood compatibility of traditional endotoxin adsorbents have been solved, thus opening a new route to fabricate absorbents for blood purification.

A Copper Coordination Polymer with Matching Energy Level for Modifying Hole Transport Layers to Improve the Performance of Perovskite Solar Cells.

Spiro-OMeTAD is currently the most widely used hole transport material for the preparation of high-performance perovskite solar cells (PSCs), usually requiring the addition of additives to achieve the desired electronic conductivity. However, the quality of the film is degraded owing to the addition of additives. Holes and defects can be observed, and the dispersion of the additives are uneven inside. Here, a copper coordination polymer, Cu-bix, with matching energy level and fluorescent properties was screened for use as an additional additive to dope Spiro-OMeTAD. The doping of Cu-bix effectively improved the dispersion state of the additives in the hole transport layers and alleviated the aggregation of LiTFSI (lithium bis(trifluoromethanesulfonyl)imide) or/and lithium salt complexes in the film. Owing to better dispersion of the additives, Spiro-OMeTAD was more fully and uniformly oxidized whereas the possibility of charge recombination was reduced in the devices. Furthermore, the flat and tightly bonded film layer obtained by optimization of the doping amount can efficiently transfer holes from the perovskite layers to the hole transport layers. Possible interaction mechanisms between additives and the copper coordination polymer are proposed and discussed. The resulting power conversion efficiency (PCE) for Cu-bix-doped PSCs was improved from 16.52 % to 18.47 % compared to the pristine devices, and this type of PSCs also showed a long stability in air owing to the increased hydrophobicity of the Cu-bix-based hole transport layers.