Tailoring Drug Release Kinetics by the Design and Optimization of Substituents in Azobenzene Molecules in the Photosensitive Liposomal System.

A light-sensitive moiety, e.g., azobenzene, for the light-sensitive liposomal drug carrier has shown advantages as an advanced drug delivery system in site-specific smart therapy due to its reversible photoisomerization characteristics. In this work, a series of 4-position-cholesterol-functionalized azobenzene derivatives with 4'-position substituted pyridine, quinoline, isoquinoline, triethylamine, or ethylenediamine were synthesized, and the relationship between the molecular structure and drug release behaviors was clarified. We found that the charge and electrophilicity of substituents were two important factors (expressed as the characteristic time) that can precisely regulate the isomerization ratio in the liposomal system. There was an approximately linear correlation between the characteristic time of photoisomerization and the fitted first-order constant of photoinduced drug release rate. The photoinduced drug release could be achieved at the desired time and in an appropriate amount by tailoring the substituents at the 4'-position of azobenzene-cholesterol derivatives.

4D printed tri-segment nerve conduit using zein gel as the ink for repair of rat sciatic nerve large defect.

Zein has enormous potential for application in biomedical field due to biodegradation and biocompatibility, we have recently prepared zein gel as a possible 3D printing ink. Our previous studies found that the pore structure in zein material can reduce early inflammation, promote the polarization of macrophages toward the M2 phenotype, and accelerate nerve regeneration. To further explore the role of zein in nerve repair, we used 4D printing technique to create nerve conduits with zein protein gel, and designed 2 types of tri-segment conduits with different degradation rates. Structural parts printed in support baths with higher water content show faster degradation rates than those printed in support baths with lower water content. The conduits that degraded quickly at both ends and slowly in the middle (CB75-CB40-CB75) and the conduits that degraded slowly at both ends and quickly in the middle (CB40-CB75-CB40) were 4D printed, respectively. Animal experiments suggest that the CB75-CB40-CB75 conduit is better for nerve repair, which may be because its degradation pattern can match to the pattern of nerve regeneration better. Our new strategy through 4D printing indicated that fine modulation in conduit degradation can affect efficacy of nerve repair significantly.

Injectable zein gel with in situ self-assembly as hemostatic material.

Zein is a biocompatible and biodegradable corn protein with promising properties for biomedical applications. It is hydrophobic with the ability to self-assemble in an aqueous medium. It can also form a gel in hydroalcoholic solvents at higher concentrations. Few studies have investigated the biomedical significance of zein gels. Herein, we exploited the injectability and water-responsive increase in stiffness of zein gel to achieve hemostasis by physical blockage of the wound and clot formation. The release of components from the gel further aided blood clotting and gave a higher clot strength than a natural clot, which can prevent rebleeding. Rabbit aortic injury and swine femoral artery injury models were used to evaluate the hemostatic efficacy of the zein gel. Zein gel was effective in both hemostatic models without applying external compression due to an in situ increase in stiffness, while the control (Celox™ Gauze) required external compression at the wound site. The zein gel was easily removed after hemostasis due to hydrophobic self-assembly. Overall, zein gel is proposed as an effective hemostatic product for any wound shape owing to its good shape adaptability and rapid in situ blood-responsive stiffness increase.

Water-responsive 4D printing based on self-assembly of hydrophobic protein "Zein" for the control of degradation rate and drug release.

Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.

Microstructure Evolution and Performance Improvement of Silicon Carbide Ceramics via Impregnation Method.

The high topological silicon carbide (SiC) ceramics can be prepared by stereolithography (SLA) combined with liquid silicon infiltration (LSI) techniques. This paper aims to enhance the performance of SiC ceramics prepared by SLA and LSI techniques via the cyclic impregnation/carbonization of the precursor of carbon source solution before LSI. The effects of impregnation/carbonization cycles on the microstructure and properties of C/SiC preform and sintered body were analyzed in detail. The results show that, with the increase of impregnation/carbonization cycles, the porosity in the C/SiC preform decreases obviously and the content of secondary SiC in the sintered body increases effectively. Especially, when the impregnation/carbonization cycle was performed twice, the sintered body had the optimal mechanical properties. The value of flexural strength, bulk density and elastic modulus were 258.63 ± 8.33 MPa, 2.95 ± 0.02 g/cm3 and 425.16 ± 14.15 GPa, respectively. In addition, the thermal dimensional stability of sintered body was also improved by this method. This method proves that SiC ceramics prepared by SLA combined with LSI have the potential of applications in space optical mirrors.

Preparation and evaluation of chitosan/polyvinylpyrrolidone/zein composite hemostatic sponges.

Trauma-related excessive bleeding is one of the leading causes of death. Chitosan (CS) sponges have unique advantages in the treatment of massive bleeding, but their application is limited by poor stability and toxic crosslinking agent. In this work, chitosan/polyvinylpyrrolidone/zein (CS/PVP/Zein) sponges with macroporous structure were prepared, which exhibited rapid water absorption capacity and water-triggered expanding property with low cytotoxicity and low hemolysis ratio. In vitro blood coagulation experiments showed that CS/PVP/Zein sponges could clot blood significantly faster than commercial surgical gauze. Further investigation of the hemostatic mechanism suggested that the CS/PVP/Zein sponges could accelerate coagulation by promoting attachment of erythrocytes, activation of platelets, and rapid plasma protein absorption. Prepared sponges were also found effective in the rat femoral artery transection model to control bleeding. Overall, the CS/PVP/Zein sponges exhibited the potential to control trauma-related hemorrhage.

Additive manufacturing of SiBCN/Si3N4w composites from preceramic polymers by digital light processing.

The application of advanced ceramic materials is limited by their brittleness and complicated manufacturing methods. Three-dimensional (3D) printing has emerged as a new method for the fabrication of complex-shaped ceramics. Herein, a type of printable slurry composed of SiBCN preceramic polymers and high-volume fractions of Si3N4 whiskers (up to 60 wt% of polymer) was prepared, and subsequently printed via digital light processing (DLP) technology. We successfully manufactured complex-structured ceramic composites and achieved high bending strength (∼180 MPa). The linear shrinkage and mass loss of the ceramic material were both significantly reduced after the introduction of whiskers. The properties and structure of the printed parts pyrolyzed at different temperatures were compared, and the relationship between the microstructure and mechanical properties discussed.

Characterization and antibacterial mechanism of poly(aminoethyl) modified chitin synthesized via a facile one-step pathway.

This work aims to synthesize poly(aminoethyl) modified chitin (PAEMC) and ascertain its antibacterial activity and mechanism. FTIR and 1H NMR results proved aminoethyl moieties were grafted to C6OH and C3OH on chitin backbone in the form of polymerization. XRD and TG/DTG analyses manifested its well-defined crystallinity and thermostability. PAEMC, with average molecular weight (MW) of 851.0 kDa, degree of deacetylation (DD) of 27.95%, and degree of substitution (DS) of 1.77, had good solubility in aqueous solutions over the pH range of 3-12, and also possessed high antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus proteus, and Klebsiella pneumoniae, commonly causing chronic wound infections. Nucleic acid release, protein leakage, increased inner membrane permeability, and decreased cell surface hydrophobicity implied bacterial cytomembranes were substantially compromised in the presence of PAEMC. Microscopically, PAEMC visually perturbed bacteria, illustrating deformed and even collapsed morphologies. Overall, PAEMC possessed good solubility, effectively destroyed bacteria via a membrane damage mechanism, and might serve as an antibacterial agent for treatments of chronic wound infections.

Hierarchically Porous Zirconia Monolith Fabricated from Bacterial Cellulose and Preceramic Polymer.

A hierarchically porous zirconia (ZrO2) monolith was successfully fabricated by using bacterial cellulose (BC) as a biotemplate and preceramic polymer as a zirconium resource, via freeze-drying and two-step calcination process. Images of scanning electron microscopy showed that the ZrO2 monolith well-replicated a three-dimensional reticulated structure of pristine BC and possessed good morphology stability till 1100 °C in air. Results of N2 adsorption/desorption and mercury porosimetry analysis revealed the hierarchically porous structure and large specific area (9.7 m2·g-1) of the ZrO2 monolith, respectively. Patterns of X-ray powder diffraction indicated that the monoclinic phase and tetragonal phase coexisted in the ZrO2 monolith with the former as the main phase. In addition, the ZrO2 monolith possessed low bulk density (0.13 g·cm-3) and good mechanical strength. These properties suggest that the as-prepared ZrO2 monolith has a great potential to serve as an ideal catalyst or catalyst support.

Synthesis, characterization, and evaluation of poly(aminoethyl) modified chitosan and its hydrogel used as antibacterial wound dressing.

This study aims to develop new antibacterial hydrogel wound dressings composed of poly(aminoethyl) modified chitosan (PAEMCS). FTIR, 1H NMR, and elemental analysis demonstrated that PAEMCS was successfully synthesized via grafting poly(aminoethyl) groups onto hydroxyl groups on chitin first, and removing acetyl groups from the grafted polymer afterward. XRD and TGA implied its well-defined crystallinity and thermostability. Furthermore, a series of hydrogels were fabricated under the participation of dipotassium hydrogen phosphate (DHP). The gelation tests suggested that the higher concentration of PAEMCS or DHP was beneficial to the formation of hydrogels. The pH values of hydrogels at 37°C were all in the range of 7.12-7.50. The rheological tests indicated that PAEMCS-based hydrogels were of lower DHP addition and higher elasticity than CS-based hydrogels to achieve the same gelation temperature under the same polymer's concentration. Additionally, the swelling, anti-bacteria, and cytotoxicity experiments showed that PAEMCS-based hydrogels possessed excellent hygroscopicity, high antibacterial activity against E. coli, S. aureus, or S. epidermidis, and good cytocompatibility toward L929 cells or HUVECs, respectively. All the results implied that PAEMCS-based hydrogels not only maintained inherent multiple properties of chitosan but also possessed excellent antibacterial activity, and might be promising antibacterial hydrogel dressings used in wound therapy.

Heterotrophic nitrogen removal by a newly-isolated alkalitolerant microorganism, Serratia marcescens W5.

A new microbe, Serratia marcescens W5 was successfully isolated. Its feasibility in purification of excessively nitrogen-containing wastewater was evaluated using inorganic nitrogen media. Single factor tests showed that W5 exhibited high ammonium removal rates (above 80%) under different culture conditions (pH 7-10, C/N ratios of 6-20, 15-35°C, 0-2.5% of salinity, respectively). Besides various organic carbon sources, W5 was able to utilize calcium carbonate with 28.05% of ammonium removed. Further experiments indicated that W5 was capable of resisting high-strength ammonium (1200mg/L) with the maximum removal rate of 514.13mgL(-1)d(-1). The nitrogen removal pathway of W5 was also tested, showing that both nitrite and nitrate were efficiently removed only in the presence of ammonium, with hydroxylamine as intermediate, which was different from the conventional nitrogen removal pathway. All the results verified that W5 was a good candidate for the purification of excessively nitrogenous wastewater.

Diverse genetic markers concordantly identify bovine origin Escherichia coli O157 genotypes underrepresented in human disease.

Genetic markers previously reported to occur at significantly different frequencies in isolates of Escherichia coli O157:H7 obtained from cattle and from clinically affected humans concordantly delineate at least five genetic groups. Isolates in three of these groups consistently carry one or more markers rarely found among clinical isolates.