Min He

Fabrication of metronidazole loaded poly (ε-caprolactone)/zein core/shell nanofiber membranes via coaxial electrospinning for guided tissue regeneration

To develop a biologically mimetic guided tissue regeneration (GTR) membrane with localized sustained drug release function to prevent infection, coaxial electrospinning technique was conducted to fabricate metronidazole (MNA)-loaded poly (ε-caprolactone) (PCL)/zein core/shell nanofibers. The nanofibers displayed a uniform bead-free round morphology as observed by scanning electron microscopy (SEM), and a core/shell structure as confirmed by transmission electron microscopy (TEM). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) characterizations demonstrated that the MNA was well dispersed in the nanofibers matrix. Due to the encapsulation of the hydrophobic zein, the MNA was released in a controlled, sustained manner over 4days, and the released MNA showed high antibacterial activity towards anaerobic bacteria. In addition, the encapsulation of natural zein resulted in enhanced cell adhesion and proliferation, and the loading of MNA did not show any cytotoxicity. Thus, these results demonstrated that the MNA-loaded core/shell nanofibers had the potential to be used as GTR membranes with antibacterial function for extensive biomedical applications.

Design of Antibacterial Poly(ether sulfone) Membranes via Covalently Attaching Hydrogel Thin Layers Loaded with Ag Nanoparticles

To inhibit bacteria attachment and the subsequent formation of biofilms on poly(ether sulfone) (PES) membranes, poly(sulfobetaine methacrylate)/poly(sodium acrylate) antibacterial hydrogel thin layers were covalently attached onto the membranes, followed by loading with Ag nanoparticles. In our strategy, double bonds were firstly introduced onto the PES membrane surfaces to provide anchoring sites, and then the hydrogel layers were synthesized on the membrane surfaces via UV light-initiated crosslinking copolymerization. Then, Ag ions were adsorbed into the hydrogel layers and reduced to Ag nanoparticles by sodium borohydride. The amounts of the adsorbed Ag ions were controlled by the mole ratios of carboxylate groups in the hydrogel layers. After attaching the hydrogel layers, a typical 3D porous structure was observed by scanning electron microscopy, and the surface chemical composition variations were characterized by attenuated total reflection-Fourier transform infrared spectroscopy. The live/dead staining, inhibition zone, and the optical degree of co-culture solution demonstrated that the designed surfaces could not only effectively resist bacteria attachment but also kill the surrounding bacteria Escherichia coli and Staphylococcus aureus. It was noteworthy that the strong antibacterial ability could be maintained for more than 5 weeks. Additionally, the excellent hemocompatibility of the modified membranes was confirmed by undetectable plasma protein adsorption, suppressed platelet adhesion, prolonged clotting time, low hemolysis ratio, and suppressed blood-related complement activation. Cell culture tests indicated that the membranes showed no cytotoxicity, but strong anti-cell adhesion properties. The proposed method to fabricate antibacterial hydrogel thin layers has great potential to be widely used to inhibit the formation of biofilms on various biomedical devices.

A versatile approach towards multi-functional surfaces via covalently attaching hydrogel thin layers.

In this study, a robust and straightforward method to covalently attach multi-functional hydrogel thin layers onto substrates was provided. In our strategy, double bonds were firstly introduced onto substrates to provide anchoring points for hydrogel layers, and then hydrogel thin layers were prepared via surface cross-linking copolymerization of the immobilized double bonds with functional monomers. Sulfobetaine methacrylate (SBMA), sodium allysulfonate (SAS), and methyl acryloyloxygen ethyl trimethyl ammonium chloride (METAC) were selected as functional monomers to form hydrogel layers onto polyether sulfone (PES) membrane surfaces, respectively. The thickness of the formed hydrogel layers could be controlled, and the layers showed excellent long-term stability. The PSBMA hydrogel layer exhibited superior antifouling property demonstrated by undetectable protein adsorption and excellent bacteria resistant property; after attaching PSAS hydrogel layer, the membrane showed incoagulable surface property when contacting with blood confirmed by the activated partial thromboplastin time (APTT) value exceeding 600s; while, the PMETAC hydrogel thin layer could effectively kill attached bacteria. The proposed method provides a new platform to directly modify material surfaces with desired properties, and thus has great potential to be widely used in designing materials for blood purification, drug delivery, wound dressing, and intelligent biosensors.

Super‐Anticoagulant Heparin‐Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility

In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood-related complement activation also confirm that the membranes exhibit super-anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials.

Substrate-Independent Ag-Nanoparticle-Loaded Hydrogel Coating with Regenerable Bactericidal and Thermoresponsive Antibacterial Properties

We report a Ag-nanoparticle (AgNP)-based substrate-independent bactericidal hydrogel coating with thermoresponsive antibacterial property. To attach the hydrogel coating onto model substrate, we first coated ene-functionalized dopamine on the substrate, and then the hydrogel thin layer was formed on the surface via the UV light initiated surface cross-linking copolymerization of N-isopropylacrylamide (NIPAAm) and sodium acrylate (AANa). Then, Ag ions were adsorbed into the hydrogel layers and reduced to AgNPs by sodium borohydride. The coating showed robust bactericidal ability against Escherichia coli and Staphylococcus aureus toward both contacted bacteria and the bacteria in the surrounding. Upon a reduction of the temperature below the LCST of PNIPAAm, the improved surface hydrophilicity and swollen PNIPAAm could detach the attached dead bacteria. Meanwhile, the long-lasting and regenerable antibacterial properties could be achieved by repeatedly loading AgNPs. By precisely controlling the AgNP loading amounts, the coating showed excellent hemocompatibility and no cytotoxity. Additionally, the coating could be applied to modify cell culture plate, since it could support cell adhesion and proliferation at 37 °C, while detach the cell by changing the temperature below lower critical solution temperature without the treatment of proteases. The study thus presents a promising way to fabricate thermoresponsive and regenerable antibacterial surfaces on diverse materials and devices for biomedical applications.

Inflammation-responsive self-regulated drug release from ultrathin hydrogel coating

Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin. A porous structure of the attached hydrogel layer was observed by scanning electron microscopy, and the presence of drug molecules in the hydrogel layer was confirmed by X-ray photoelectron spectroscopy and UV-vis absorption spectra. The drug release could be triggered under the mimicking inflammation environment, and the release rate was responsive to the inflammation degree. In addition, after attaching the hydrogel coating, the substrate showed low cytotoxicity, and high promotion for cell adhesion and proliferation. The excellent hemocompatibility of the hydrogel coating was also demonstrated by prolonged clotting time and suppressed platelet adhesion. This work suggests that the inflammation-responsive indometacin conjugated hydrogel coating has great potential to be used for prophylaxis HO.

Nanofibrous membranes with surface migration of functional groups for ultrafast wastewater remediation

The development of highly efficient adsorbents with a fast adsorption rate and high adsorption capacity presents an enticing prospect for wastewater remediation. In this paper, a novel ultrafast adsorption nanofibrous membrane (UFAM) for organic dyes was prepared through a simple functional group surface migration method. An amphiphilic copolymer of methyl methacrylate and sodium styrene sulfonate was synthesized in a mass ratio of 3u2006:u20062 by free radical polymerization and further blended into polyethersulfone (PES) to prepare functionalized PES nanofibrous membranes by electrospinning technology. Just by soaking in water and lyophilization, the hydrophilic and negatively charged sulfonate groups migrated and concentrated on the membrane surface, and the obtained UFAM was found to be exceptionally efficient in the removal of methylene blue (MB) dye from aqueous solution. Especially, an ultrafast adsorption rate for MB with an adsorption equilibrium time of within 5 min was reported for the first time. The mechanism of the ultrafast adsorption based on the sulfonate group migration and enrichment was also especially explored in this study. In addition, the UFAM also showed excellent performance of recyclability, dynamic filtration–purification, selective adsorption for cationic dyes from mixed dye solutions and smart filtration–separation for cationic and anionic dyes. Therefore, we envision that this study will not only provide a new strategy to construct low-cost and highly efficient adsorbents, but also demonstrate their potential applications in the removal of organic dyes on a large scale.

A self-defensive bilayer hydrogel coating with bacteria triggered switching from cell adhesion to antibacterial adhesion

We report on a self-defensive bilayer hydrogel coating which can switch from a cell adhesion surface to an antibacterial adhesion surface. To covalently attach the coating, an antifouling hydrogel thin film was firstly prepared on a thiol modified substrate as the bottom layer via the thiol–ene click reaction of the ene-functionalized copolymer of poly(sulfobetaine methacrylate-acrylate acid-2-hydroxyethyl methacrylate) (P(SBMA-AA-HEMA)). Thereafter, heparin-mimicking polymer chains were grafted onto the hydrogel film surface as the upper layer via surface initiated atom transfer radical polymerization. The ester group of HEMA was designed as the sensitive part which could be cleaved in a bacterial infectious environment, while the hydroxyl group was designed as the anchoring point of the upper layer. The surface morphology and chemical composition after each modification step were characterized by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. The bilayer coating could promote cell adhesion and proliferation, as well as bacterial adhesion. After being immersed into a cholesterol esterase solution (simulative bacterial infectious environment), the upper layer could be detached rapidly, and the exposed bottom layer then showed strong resistance to bacteria. Our approach towards bacteria-responsive “intelligent” coating gives new insights into the antibacterial protection of biomedical devices.

A substrate-independent ultrathin hydrogel film as an antifouling and antibacterial layer for a microfiltration membrane anchored via a layer-by-layer thiol–ene click reaction

Herein, a substrate-independent ultrathin hydrogel film was constructed on a microfiltration membrane through layer-by-layer (LbL) thiol-ene click chemistry to improve the antifouling and antibacterial properties. In our strategy, ene-functionalized dopamine was synthesized and coated onto a model substrate (polyethersulfone membrane) to introduce double bonds as anchoring sites for the hydrogel film; thiol-functionalized poly[oligo(ethylene glycol)mercaptosuccinate] (POEGMS) and ene-functionalized P(SBMA-co-AA) were synthesized as hydrogel precursors. The membrane was alternately immersed in the precursor solutions to form the ultrathin hydrogel film. Finally, Ag nanoparticles (AgNPs) were loaded into the hydrogel layer by adsorption and reduction procedures. By coating the hydrogel films, the loaded AgNPs could kill almost all the contacting bacteria and the bacteria in the surroundings, and the enhanced hydrophilicity of the modified membrane could effectively prevent the attachment of the bacteria. The membrane flux showed no significant decrease, the rejection ratio of BSA increased from 51% to 89%, and the FRR increased from 36% to 90%. Moreover, the improvement of the hemocompatibility was confirmed by the decline in the plasma protein adsorption, prolonged clotting times, low hemolysis ratio, and prevention of platelet adhesion. Compared with that of other techniques for attaching hydrogel films, the main advantage of the current technique is that the hydrogel film thickness could be well controlled within the nanometer range; thus, it could significantly improve the antifouling and antibacterial properties of the membrane, but without compromising its permeability. Another advantage is that it is versatile for various substrates such as PVDF, PAN, and CA. This study opens up a facile and versatile route for anchoring ultrathin hydrogel film onto polymeric membranes to achieve excellent antifouling, antibacterial and hemocompatible properties.