Covalent deposition of zwitterionic polymer and citric acid by click chemistry-enabled layer-by-layer assembly for improving the blood compatibility of polysulfone membrane.

Development of blood compatible membranes is critical for biomedical applications. Zwitterionic polymers have been proved to be resistant to nonspecific protein adsorption and platelet adhesion. In this work, two kinds of zwitterionic copolymers bearing alkynyl and azide groups are synthesized by atom transfer radical polymerization (ATRP) and subsequent reactions, namely alkynyl-poly(sulfobetaine methacrylate) (alkynyl-PSBMA) and azide-poly(sulfobetaine methacrylate) (azide-PSBMA). The copolymers are directly used to modify azido-functionalized polysulfone (PSf-N3) membrane via click chemistry-enabled layer-by-layer (LBL) assembly. Alkynyl-citric acid is then clicked onto the membrane when the outermost layer was azide-PSBMA. The chemical compositions, surface morphologies, and hydrophilicity of the zwitterionic polymer and citric acid multilayer modified membranes are characterized. The composite multilayer is resistant to protein adsorption and platelet adhesion and also prolongs clotting times, indicating that the blood compatibility is improved. Moreover, after clicking the small molecule anticoagulant alkynyl-citric acid onto the outermost of the zwitterionic multilayer, the membrane shows further improved anticoagulant property. The deposition of zwitterionic polymer and citric acid via click chemistry-enabled LBL assembly can improve the blood compatibility of the PSf membrane.

Zwitterionic polymer functionalization of polysulfone membrane with improved antifouling property and blood compatibility by combination of ATRP and click chemistry.

The chemical compositions are very important for designing blood-contacting membranes with good antifouling property and blood compatibility. In this study, we propose a method combining ATRP and click chemistry to introduce zwitterionic polymer of poly(sulfobetaine methacrylate) (PSBMA), negatively charged polymers of poly(sodium methacrylate) (PNaMAA) and/or poly(sodium p-styrene sulfonate) (PNaSS), to improve the antifouling property and blood compatibility of polysulfone (PSf) membranes. Attenuated total reflectance-Fourier transform infrared spectra, X-ray photoelectron spectroscopy and water contact angle results confirmed the successful grafting of the functional polymers. The antifouling property and blood compatibility of the modified membranes were systematically investigated. The zwitterionic polymer (PSBMA) grafted membranes showed good resistance to protein adsorption and bacterial adhesion; the negatively charged polymer (PNaSS or PNaMAA) grafted membranes showed improved blood compatibility, especially the anticoagulant property. Moreover, the PSBMA/PNaMAA modified membrane showed both antifouling property and anticoagulant property, and exhibited a synergistic effect in inhibiting blood coagulation. The functionalization of membrane surfaces by a combination of ATRP and click chemistry is demonstrated as an effective route to improve the antifouling property and blood compatibility of membranes in blood-contact.

Graphene oxide linked sulfonate-based polyanionic nanogels as biocompatible, robust and versatile modifiers of ultrafiltration membranes.

Aiming to enhance the current biological performances of ultrafiltration membranes, in this study, a new kind of graphene oxide linked sulfonate-based polyanionic nanogel (GO-SPN) was fabricated by free radical cross-linked copolymerization. Then, GO-SPN embedded polyethersulfone (PES/GO-SPN) ultrafiltration (UF) membranes were achieved through one-pot PES dissolution and interpenetration, followed by a liquid-liquid phase inversion method. The GO-SPN modified UF membranes exhibited increased porous cross-section structures with a pH-dependent water flux. Notably, the modified UF membranes showed excellent in vitro hemocompatibility and cytocompatibility performances, such as good anti-coagulant activity, red blood cell compatibility (with very low hemolysis ratios below 0.2%), anti-platelet adhesion and activation, low inflammation potential, and high endothelial cell compatibility. Moreover, to confirm the actual application potential of the GO-SPN embedded membranes in diverse fields, we also examined the performances of PES/GO-SPN composite hollow fiber UF membranes. It was validated that the mechanical properties of the hollow fiber UF membranes (tensile strength higher than 1.2 MPa) could satisfy the demands of industrial or clinical applications. Furthermore, the modified membranes exhibited versatile ability, i.e. they could load Ag-nanoparticles which bestowed them with excellent bactericidal capability (about 97%) against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Due to the integration of hemo- and cyto-compatibility, good mechanical strength as well as bactericidal capability, the GO-SPN embedded membranes offer a new protocol to greatly extend the application potential of UF membranes in fields ranging from clinical hemodialysis to water purification.

Graphene oxide and sulfonated polyanion co-doped hydrogel films for dual-layered membranes with superior hemocompatibility and antibacterial activity.

In this study, a new kind of hemocompatible and antibacterial dual-layered polymeric membrane was fabricated by coating a top layer of graphene oxide and a sulfonated polyanion co-doped hydrogel thin film (GO-SPHF) on a bottom membrane substrate. After a two-step spin-coating of casting solutions on glass plates, dual-layered membranes were obtained by a liquid-liquid phase inversion method. The GO-SPHF composite polyethersulfone (PES) membranes (PES/GO-SPHF) showed top layers with obviously large porous structures. The chemical composition tests indicated that there were abundant hydrophilic groups enriched on the membrane surface. The examination of membrane mechanical properties indicated that the composite membranes exhibited only slightly decreased performance compared to pristine PES membranes. Moreover, to validate the potential applications of this novel dual-layered membrane in diverse fields, we tested the hemocompatibility and antibacterial activity of the membranes, respectively. Notably, the PES/GO-SPHF membranes showed highly improved in vitro hemocompatibility, such as good anti-coagulant activity, suppressed platelet adhesion and activation, low inflammation potential, and good red blood cell compatibility. Furthermore, the dual-layered membranes exhibited robust antibacterial ability after in situ loading of Ag-nanoparticles with excellent bactericidal capability to both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Due to the integration of the porous membrane structure, good mechanical strength, excellent hemocompatibility, as well as robust bactericidal capability, the GO and sulfonated polyanion co-doped dual-layered membranes may open up a new protocol to greatly demonstrate the potential application of polymeric membranes for clinical hemodialysis and many other biomedical therapies.

[Effect of blood purification materials and anticoagulants on the contact activity of factor XI].

OBJECTIVE: This study was conducted to examine the degree of contact activation of five blood purification materials sulfonated polyethersulfone (PES-SO3Na), polyethersulfone (PES), polysulfone (PS), polymethylmethacrylate (PMMA) and cellulose acetate (CA) after they were incubated in anticoagulant-containing human plasma for 10 minutes at 37 degrees C. METHODS: Three anticoagulants Heparin, Trisodium citrate and Disodium EDTA were used. The time course for generation of FXII activity by the materials after incubation in anticoagulant-containing human plasma was evaluated. The degree of contact activation was determined by measuring membrane-bound alpha-FXIIa activity level. RESULTS: (1) The five materials caused different increase at different rate in the generation of alpha-FXIIa after they were separately incubated with each of the three anticoagulants. (2) PES-SO3Na activated the least FXII no matter which anticoagulant the plasma contained. CONCLUSION: Contact activation can be mediated by antithrombotic agent. PES-SO3Na has the best blood compatibility with respect to contact activation considering intrinsic coagulation.

Surface hydrophilic modification of polyethersulfone membranes by surface-initiated ATRP with enhanced blood compatibility.

Surface-initiated atom transfer radical polymerization (SI-ATRP) was used to tailor the functionality of polyethersulfone (PES) membranes. A two-step method including nitration reaction and amination reaction was used to synthesize aminated polyethersulfone (PES-NH2) for the preparation of PES/PES-NH2 membranes. Covalently tethered hydrophilic polymer brushes of poly(N-vinylpyrrolidone) (PVP) were prepared via SI-ATRP at low temperature in an aqueous solvent. Attenuated total reflection-Fourier transform infrared (ATR-FTIR), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), and water contact angle were used to characterize the modified membranes surfaces. The PVP-grafted PES membranes showed lower protein adsorption and suppressed platelet adhesion compared with the pristine PES membrane. Moreover, the activated partial thromboplastin time (APTT) for the PVP-grafted PES membranes was increased. These results indicated that the surface hydrophilic modification by grafting PVP brushes provided practical application for the PES membranes with good blood compatibility.

[The comparisive study of the clinical effect of rotary self-locking intramedullary nail and intramedullary interlocking nail for the treatment of femur fracture].

OBJECTIVE: To compare the clinical effect of rotary self-locking intramedullary nail (RSIN) and intramedullary interlocking nail (IIN) for the treatment of fresh femoral shaft fracture. METHODS: The radiological records of 60 fresh femoral shaft fractures (41 stable fractures and 19 unstable fractures) were retrospectively analyzed. Among them, 49 were male and 11 were female. The average age was 33.5 years old (range from 12 to 68 years old). All cases were fresh fracture with no important blood vessel or nerve injury, which were taken operation with RSIN on IIN respectively in 2 h-7 d after injury. The patients in IIN group began functional movements at postoperative 4 to 5 days and could bear the weight of 10-15 kg. The patients in RSIN group could began functional exercises after the wound healed and bear partly weight after 6 weeks. Both groups were contrasted on the biomechanics, operation procedure, fracture healing time, functional recovery and operative indication. RESULTS: Both groups were followed-up for average 13 months. IIN group: the average healing time of closed femur fracture was 16 weeks while that of open fracture was 20 weeks. The healing rate was 100% and the malunion rate was 7.9%. The excellent and good rate of functional recovery was 93.3% including excellent in 27 cases, good in 1, fair in 1 and bad in 1. RSIN group: the average healing time of closed femur fracture was 16 weeks while open fracture was 23 weeks. The healing rate was 87% and the malunion rate was 18.2%. The excellent and good rate of functional recovery was 83.3% including excellent in 23 cases, good in 2, fair in 3 and bad in 2. No implant break and nonunion happened. The differences between two groups in healing time, deformity-union rate and the rate of the twice operation were statistically significant. CONCLUSION: IIN provides a reliable and practical alternative method for the treatment of all kinds of femoral shaft fracture and its important complication is fewer than RSIN group. RSIN also has a good curative effect in its own indication.