Xiaodong Xing

Covalently antibacterial alginate-chitosan hydrogel dressing integrated gelatin microspheres containing tetracycline hydrochloride for wound healing

An antibacterial and biodegradable composite hydrogel dressing integrated with microspheres is developed for drug delivery and wound healing. The mechanism of gelation is attributed to the Schiff-base reaction between aldehyde and amino groups of oxidized alginate (OAlg) and carboxymethyl chitosan (CMCS). To enhance antibacterial and mechanical properties, tetracycline hydrochloride (TH) loaded gelatin microspheres (GMs) were fabricated by an emulsion cross-linking method, followed by integrating into the OAlg-CMCS hydrogel to produce a composite gel dressing. In vitro gelation time, swelling, degradation, compressive modulus and rheological properties of the gel dressing were investigated as the function of microsphere ratios. With increasing ratios of microspheres from 10 to 40mg/mL, the composite dressing manifested shorter gelation time and lower swelling ratios, as well as higher mechanical strength. Comparing to other formulations, the gel dressing with 30mg/mL microspheres showed more suitable stabilities and mechanical properties for wound healing. Also, in vitro drug release results showed that the loaded TH could be sustained release from the composite gel dressing by contrast with pure hydrogels and microspheres. Furthermore, powerful bacteria growth inhibition effects against Escherichia coli and Staphylococcus aureus suggested that the composite gel dressing, especially the one with 30mg/mL GMs containing TH, has a promising future in treatment of bacterial infection.

Fabrication of charge reversible graphene oxide-based nanocomposite with multiple antibacterial modes and magnetic recyclability

In this work, N-alkylated poly (4-vinylpyridine) (NPVP), a cationic polymer, was firstly applied for the surface modification of Fe3O4 nanoparticles. Then the modified Fe3O4 nanoparticles (Fe3O4@NPVP NPs) combined with graphene oxide (GO) through simple electrostatic binding. Subsequently, deposited Ag nanoparticles (Ag NPs) procedure was carried out to form the multiple antibacterial nanocomposites (GO-Fe3O4@NPVP-Ag). The synthesized nanostructures were well characterized by Transmission Electron Microscope (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared (FT-IR) and Raman spectroscopy. The zeta potentialmeasurement showed that the novel antibacterial nanocomposites exhibited a capacity of reversing its surface charge from negative (physiological pH) to positive (acidic condition). Furthermore, the incorporation of magnetic Fe3O4 NPs into the nanosystems facilitates the cyclic utilization of GO-Fe3O4@NPVP-Ag by magnetic separation. The antibacterial properties of GO-Fe3O4@NPVP-Ag nanocomposites were evaluated with Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Moreover, the cytotoxicity of GO-Fe3O4@NPVP-Ag nanocomposites was studied using NIH-3T3 cells. The results showed that the GO-Fe3O4@NPVP-Ag nanocomposites exhibited excellent antibacterial properties and low cytotoxicity, thus confirming its application as a promising rapid bactericide in various antibacterial fields.

Facile synthesis of cationic polymer functionalized nanodiamond with high dispersity and antibacterial activity

In this work, a cationic polymer, N-alkylated poly (4-vinylpyridine) was applied for the surface functionalization of nanodiamond (ND). The facile route not only settled the problems of agglomeration and poor dispersion stability of ND but also rendered the nanomaterial antibacterial property. Chemical modification of the particles was confirmed by FT-IR spectroscopy and 1HNMR, and the cationic polymer contents were determined by TGA studies. The particle diameters and dispersity of functionalized NDs were investigated by TEM and DLS measurements. It was found that extremely tight core aggregates (100–200xa0nm) were broken into tiny nanoparticles (20–30xa0nm) through functionalization with NPVP-propyl or NPVP-hexyl, which gave stable and homogeneous functionalized ND particles in colloidal solution. The antibacterial tests against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) showed that the cationic polymer-modified ND exerted certain antibacterial activity. The FE-SEM images indicated that NPVP-hexyl-ND particles were attached to the cell wall surface of E. coli, which subsequently led to the formation of nanoscale holes on cell membrane and eventually the serious destruction of cell wall. We suspected that the interaction of NPVP-hexyl-ND with bacteria may come from the electrostatic interactions, the intermolecular and surface forces between functionalized nanoparticles and cell membranes, which may damage the outer membranes of bacteria and result in cell death.

Silver nanoparticle and lysozyme/tannic acid layer-by-layer assembly antimicrobial multilayer on magnetic nanoparticle by an eco-friendly route

A facile, economical and green synthetic route was developed to fabricate magnetic nanocomposite arming with silver nanoparticles (AgNPs) for antibacterial application. In this synthesis, two natural compounds, positively charged lysozyme (Lys) and negatively charged tannic acid (TA), were alternately deposited on Fe3O4 nanoparticles (IONPs) surface by layer-by-layer (LbL) self-assembly technique. And then AgNPs were embedded by an in situ reduction of Ag+ so as to achieve complementary antibacterial functions to act against Gram-positive and Gram-negative bacteria. In which, the deposition of AgNPs can be facilely achieved without any external reducing agent. The systematic antibacterial assays showed that synthesized nanocomposites had high antibacterial efficiency against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Investigation of antimicrobial mechanism suggested that these nanocomposites could lead to the disorganization of bacterial cytomembrane and leakage of cytoplasmic contents. Moreover, the permeable alteration of cytoplasmic membrane may facilitate the Ag+ released from nanocomposite entering into cells, and further cause the bacterial death. Due to the excellent magnetic responsive performance of IONPs, the nanocomposites can be easy recovery by external magnetic field from application environment after disinfection. By taking advantages of such properties, the developed nanocomposite could be an ideal candidate with promising antibacterial applications.

Development of a novel resin-based dental material with dual biocidal modes and sustained release of Ag+ ions based on photocurable core-shell AgBr/cationic polymer nanocomposites

Research on the incorporation of cutting-edge nano-antibacterial agent for designing dental materials with potent and long-lasting antibacterial property is demanding and provoking work. In this study, a novel resin-based dental material containing photocurable core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) was designed and developed. The shell of polymerizable cationic polymer not only provided non-releasing antibacterial capability for dental resins, but also had the potential to polymerize with other methacrylate monomers and prevented nanoparticles from aggregating in the resin matrix. As a result, incorporation of AgBr/BHPVP nanocomposites did not adversely affect the flexural strength and modulus but greatly increased the Vicker’s hardness of resin disks. By continuing to release Ag+ ions without the impact of anaerobic environment, resins containing AgBr/BHPVP nanoparticles are particularly suitable to combat anaerobic cariogenic bacteria. By reason of the combined bactericidal effect of the contact-killing cationic polymers and the releasing-killing Ag+ ions, AgBr/BHPVP-containing resin disks had potent bactericidal activity against S. mutans. The long-lasting antibacterial activity was also achieved through the sustained release of Ag+ ions due to the core-shell structure of the nanocomposites. The results of macrophage cytotoxicity showed that the cell viability of dental resins loading less than 1.0u2009wt% AgBr/BHPVP was close to that of neat resins. The AgBr/BHPVP-containing dental resin with dual bactericidal capability and long term antimicrobial effect is a promising material aimed at preventing second caries and prolonging the longevity of resin composite restorations.Graphical Abstract

Immobilization of N-Halamine Based Polycation on Nanodiamonds for High Dispersity and Enhanced Biocidal Activity

Novel bactericidal materials, polycation-based N-halamine functionalized nanodiamonds (PCN-NDs), were fabricated by coating of nanodiamonds (NDs) with quaternarized N-halamine polymers via a facile approach. Chemical modification of the particles was confirmed by FTIR, XPS and TGA. The particle diameters and dispersity of the functionalized NDs were investigated by TEM and DLS measurements. It was found that ND tight core aggregates could be broken into tiny nanoparticles with 40-50 nm through functionalization procedure, which resulted in stable colloidal dispersion solution over one month. The antibacterial tests showed that the PCN-NDs exhibited enhanced antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) compared with their bulk counterparts. The minimum inhibitory concentration values of the as-prepared PCN-NDs are 62.5 μg/mL for both E. coli and S. aureus, even PCN-NDs eliminated nearly 100% of E. coil and S. aureus (107-108 CFU/mg nanoparticles) within 15 min. Furthermore, the as-prepared antimicrobial PCN-NDs exhibited good storage stability and regenerability.

Synthesis of chitosan/poly (ethylene glycol)-modified magnetic nanoparticles for antibiotic delivery and their enhanced anti-biofilm activity in the presence of magnetic field

Biocompatible Fe3O4/chitosan (CS)/poly (ethylene glycol) (PEG)/gentamicin (Gent) magnetic nanoparticles, namely Fe3O4@PEG-Gent NPs, have been successfully developed for antibiotic delivery. In which, PEG dicarboxylic acid was used to modify Fe3O4 NPs for good dispersity as well as offer sufficient carboxyl groups as binding sites. And then the free Gent was facilely loaded onto Fe3O4 NPs so as to achieve powerful antibacterial activity via electrostatic interactions. Under acidic condition, the CS and PEG of Fe3O4@PEG-Gent were protonated to introduce the positive charge to NPs surface, thus facilitating the contact with negatively charged bacterial cell membrane. What is more, the stretches of CS chains triggered by acidic pH may prevent the antimicrobial efficiency of Gent from weakening. Compared with the free antibiotic, these nanocomposites presented better antimicrobial efficacy against gram-positive bacteria S. aureus under acidic condition. Intriguingly, the confocal laser scanning macroscopy imaging suggested that the anti-biofilm efficacy of nanocomposites was significantly enhanced in the presence of an external magnetic field. Due to the superparamagnetic performance of Fe3O4 NPs, these nanocomposites were allowed deeper penetration into a mature biofilm of S. aureus by magnetic field, leading to an effective Gent delivery for eradication of biofilm. The ingenious fabrication of the antibiotic delivery system not only efficiently improved the effectiveness and bioavailability of Gent at acidic media, but also provided an innovative platform to treat bacterial biofilms-associated infection by applying extra environmental factors such as magnetic field.

Mussel-inspired deposition of copper on titanium for bacterial inhibition and enhanced osseointegration in a periprosthetic infection model

Periprosthetic infection represents one of the most devastating complications in orthopedic surgeries. Implants that have both anti-bacterial and bone-forming capability and may function to simultaneously clear infection and repair bone defect, therefore, are highly desirable. In this study, titanium (Ti) substrates were fabricated deposited with different amounts of copper (Cu) using polydopamine (PDA)-based chemical modification technology. In vitro, Ti implants that were treated with PDA and deposited with Cu (Ti-PDA-Cu) showed excellent antibacterial performance against both S. aureus and E. coli compared with pristine Ti. They also markedly promoted adhesion and spreading of MC3T3-E1 cells, implying good biocompatibility of such Ti-PDA-Cu materials. In vivo, results from an animal model of implant-related osteomyelitis clearly demonstrated that Ti-PDA-Cu implants not only effectively inhibited bacterial infection, but also promoted osseointegration at the bone/implant interface. Taken together, these findings show that Ti-PDA-Cu possesses outstanding biocompatibility and antibacterial activity, and are candidate materials for preventing periprosthetic infection.

Designing of membrane-active nano-antimicrobials based on cationic copolymer functionalized nanodiamond: Influence of hydrophilic segment on antimicrobial activity and selectivity

Designing cationic nano-antimicrobial is a promising solution for combating drug resistant microbes. In this work, hydrophilic cationic copolymer was applied for the surface functionalization of nanodiamonds (NDs) aiming at developing a highly membrane-active nano-antibacterial agent with satisfactory selectivity. As a result, after functionalization, the increased repulsive forces within NDs and interaction with solvent molecular network made the heavily aggregated pristine NDs break down into tiny nanoparticles with particle size ranging from 10 to 100u202fnm. The improved hydrophilicity and enlarged surface area endowed QND-H5 and QND-H10 a powerful bactericidal capability toward both of Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In the further bactericidal assessment, it was also demonstrated that the formation of hydrogen bonding between the 2-hydroxyethyl methacrylate (HEMA) side chains and lipid head groups of bacterial membrane also contributed to the enhanced bactericidal ability. Field emission scanning electron microscopy analysis confirmed that as-prepared nano-hybrid acted bactericidal ability via physical nature of outer membrane and cytoplasmic membrane-separating destruction mechanism toward E. coli, which may derive from the hydrogen bonding ability, making them more effective toward bacterial. More importantly, it was found that with just 10% of HEMA, QND-H10 displayed good selectivity toward bacteria over mammalian cells as shown by the high HC50 values with relatively low MIC values, suggesting the great potential application in medical fields. These results indicate that hydrogen bonding is an important element to achieve the desired high antibacterial activity and selectivity, particularly when cationic nano-antibacterial agents are required for medical application.

Novel resin-based dental material with anti-biofilm activity and improved mechanical property by incorporating hydrophilic cationic copolymer functionalized nanodiamond

AbstractThere is an increasing clinical need to design dental restorative materials that combine excellent mechanical property and anti-biofilm activity. In the current study, photocurable polycation functionalized nanodiamond (QND) was synthesized and proposed as novel filler for dental resins. By reason of increased repulsive force between nanoparticles and enhanced compatibility with resin matrix, QND dispersed uniformly in reinforced resins, which would help to transfer stress and deformation from the matrix to fillers more efficiently, resulting in a significant improvement in mechanical properties. Notably, the Vickers’s hardness, flexural strength and flexural modulus of resins containing 1.0u2009wt% QND were 44.5, 36.1 and 41.3% higher than that of control, respectively. The antibacterial activity against Streptococcus mutans (S. mutans) showed that QND-incorporated resins produced anti-adhesive property due to their hydrophilic surfaces and could suppress bacterial growth as a result of the contact-killing effect of embedded nanocomposites. As the synergistic effect of anti-adhesive and bactericidal performance, resins loading 1.0~1.5u2009wt% QNDs displayed excellent anti-biofilm activity. Meanwhile, the results of macrophage cytotoxicity showed that the proliferation of RAW 264.7 cells remained 84.3%, even at a concentration of 1.0u2009wt% QNDs after 7-day incubation. Therefore, the QND-containing dental resin with the combination of high mechanical property, bacteria-repellent capability and antibacterial performance holds great potential as a restorative material based on this scheme.n