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Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries. [ABSTRACT FROM AUTHOR]

The development of broad-spectrum anti-bacterial tough hydrogels without antibiotics remains a challenge in biomedical applications. In this study, we have synthesized a novel tough anti-bacterial complex hydrogel based on Cu2+ coordination. A swollen and weak poly(acrylamide-co-4-vinylbenzyl-(trihydroxymethyl-phosphonium)chloride) (P(AAm-co-VBzTHPC)) hydrogel was prepared by the radical copolymerization of AAm and VBzTHPC monomer solutions, followed by immersion in CuSO4 solution to coordinate with Cu2+ to form a strong and tough hydrogel. Fourier transform infrared (FTIR) spectra and X-ray photoelectron spectra (XPS) were used to characterize the coordination structure between phosphorus and oxygen atoms in the VBzTHPC monomer and copper ions. The water content and mechanical properties of the obtained hydrogel varied with gel composition. The prepared toughened hydrogel exhibited excellent anti-bacterial performance because of the introduction of copper ion coordination and the slow release of copper ions, with bacterial viability of 5.1% when the mole fraction of VBzTHPC was 10 mol%. Cell viability when cocultured with the toughened hydrogel was above 85% using the Cell Counting Kit-8 (CCK-8) method, indicating the good biocompatibility of the hydrogel. Compared with the control group experiment in vivo, this tough hydrogel can also promote wound healing, making it a promising candidate for wound dressing. [ABSTRACT FROM AUTHOR]

Thrombus and restenosis after stent implantation are the major complications because traditional drugs such as rapamycin delay the process of endothelialization. Nitric oxide (NO) is mainly produced by endothelial nitric oxide synthase (eNOS) on the membrane of endothelial cells (ECs) in the cardiovascular system and plays an important role in vasomotor function. It strongly inhibits the proliferation of smooth muscle cells (SMCs) and ameliorates endothelial function when ECs get hurt. Inspired by this, introducing NO to traditional stent coating may alleviate endothelial insufficiency caused by rapamycin. Here, we introduced SNAP as the NO donor, mimicking how NO affects in vivo, into rapamycin coating to alleviate endothelial damage while inhibiting SMC proliferation. Through wicking effects, SNAP was absorbed into a hierarchical coating that had an upper porous layer and a dense polymer layer with rapamycin at the bottom. Cells were cultured on the coatings, and it was observed that the injured ECs were restored while the growth of SMCs further diminished. Genome analysis was conducted to further clarify possible signaling pathways: the effect of cell growth attenuated by NO may cause by affecting cell cycle and enhancing inflammation. These findings supported the idea that introducing NO to traditional drug-eluting stents alleviates incomplete endothelialization and further inhibits the stenosis caused by the proliferation of SMCs. [ABSTRACT FROM AUTHOR]

Phosphorylcholine (PC) based polymer coatings with excellent biocompatibility have shown successful commercialization in drug-eluting stents. However, poor degradability represents a challenge in the application of biodegradable stents. Herein, a biodegradable phosphorylcholine copolymer is developed based on one-step radical ring-opening polymerization (RROP). This copolymer was synthesized by copolymerization of a PC unit, degradable ester (2-methylene-1,3-dioxepane, MDO) unit and non-degradable butyl methacrylate (BMA) unit, which showed ratio controllability by changing the monomer ratio during polymerization. We demonstrated that the copolymer with the ratio of 34% MDO, 19% MPC and 47% BMA could form a stable coating by ultrasonic spray, and showed good blood compatibility, anti-adhesion properties, biodegradability, and rapamycin eluting capacity. In vivo study revealed its promising application as a biodegradable stent coating. This work provides a facile path to add biodegradability into PC based polymers for further bio-applications. [ABSTRACT FROM AUTHOR]

In the "post-antibiotic era", healthcare-associated infection has become a global problem that threatens public health and causes huge economic losses. The development of antibacterial coatings based on non-antibiotic strategies is particularly important as drug-resistant bacteria continue to evolve. Photodynamic coatings are a high potential method to treat bacteria, however, the aggregation of photosensitizers on the coating affects the photodynamic capacity seriously. Herein, a photodynamic coating is developed based on the host–guest interaction between β-cyclodextrin and the photosensitizer methylene blue (MB). The host–guest interaction avoids aggregation of MB and results in a high singlet oxygen quantum yield. Consequently, efficient photoantibacterial activity towards methicillin-resistant Staphylococcus aureus is achieved by the photodynamic coating with very low MB density (0.53 ± 0.06 μg cm−2). [ABSTRACT FROM AUTHOR]

Introducing wrinkling or rough features into substrates is of great practical significance to construct various functional surfaces. Due to the sensitivity of assembled units towards environmental stimuli, the internals of layer-by-layer films can be readily adjusted to generate various micro- and nanostructures. We previously described a self-roughening polyelectrolyte multilayer (PEM) to facilitate the introduction of surface microstructures. In the present work, the growth process of PEI/PAA multilayer films was investigated and the mean size of the surface microstructures was found to increase linearly with the film thickness. The spontaneous formation of these surface features can be attributed to swelling-induced film deformation during the assembling process, which is similar to the surface wrinkling of hydrogels undergoing a volume phase transition. When exposed to saturated humidity, the internal stress as well as the surface microstructures can be diminished spontaneously, leading to a flat surface over the substrates. Given the effect of the underlying film thickness on the characteristic wavelength of the surface wrinkles, multiscale surface microstructures can be readily realized by means of spatially presetting the distribution of the film thickness. [ABSTRACT FROM AUTHOR]

A constant increase of nosocomial infections that are caused by adhesion and colonization of pathogenic microorganisms, especially drug-resistant bacteria, on the surfaces of healthcare devices has received considerable attention worldwide. In this study, bioinspired by antimicrobial skins of natural living beings, we developed a self-healing bactericidal coating through the immobilization of hydrophobic antimicrobial peptides (AMPs) into a multilayer film, which was constructed through the enhanced exponential layer-by-layer assembly of polyethylenimine (PEI) and poly(acrylic acid) (PAA). The (PEI/PAA) film shows particular dynamic properties from the as-prepared thin solid film to a spongy microporous structure via acid solution treatment, and then back to the thin solid film by eliminating micropores via the treatment of saturated humidity. Consequently, the loading and integration of hydrophobic AMPs such as gramicidin A (GA) into the (PEI/PAA) film were achieved via simple wicking action with GA solution and subsequent humidity treatment, respectively. The GA loading densities can be precisely controlled by using different concentrations of GA solution. We demonstrated that the GA immobilized (PEI/PAA) film has rapid self-healing properties, and that Gram-positive bacteria S. aureus including the methicillin-resistant type were efficiently killed through the contact-killing mode. Collectively, this self-healing bactericidal coating shows practical potential in a variety of healthcare applications. [ABSTRACT FROM AUTHOR]

The stiffness of the substrates has been found to have a strong effect on cell behaviors, especially on cell adhesion, which is the first cellular event when cells contact materials. Much effort has been made to develop the materials with controlled stiffness for regulating cell adhesion. However, most available strategies for controlling the stiffness of material surfaces are generally limited to be static, which means that the stiffness is fixed during cell adhesion. Herein, we developed polyelectrolyte multilayer films (PEMs), and their stiffness can be dynamically modulated by mild stimuli. The PEMs were made by alternative deposition of poly-l-lysine (PLL) and thiol group modified hyaluronan (HA-SH) using the layer-by-layer assembly technique. The (PLL/HA-SH) multilayers can be cross-linked via oxidation of thiol groups. After crosslinking, the stiffness was increased and the adhesion of fibroblast cells was promoted. The stiffness of the multilayer films can be down-regulated dynamically by adding glutathione (GSH) in the medium, leading to in situ reduction of cell adhesion. Our study provides a promising strategy for the development of material surfaces with dynamically changeable stiffness, which is of great potential in the field of cell-based biomaterials. [ABSTRACT FROM AUTHOR]

Thin organic films containing carbon nanotubes (CNTs) have received increasing attention in many fields. In this study, a robust thin superhydrophobic film has been created by using layer-by-layer assembly of the carbon nanotubes wrapped by poly(dopamine) (CNT@PDA) and poly(ethyleneimine) (PEI). UV-vis spectroscopy, ellipsometry, and quartz crystal microbalance with dissipation (QCM-D) measurements confirmed that the sequential deposition of PEI and CNT@PDA resulted in a linear growth of the (PEI–CNT@PDA) film. This thin film contained as much as 77 wt% CNTs. Moreover, a very stable and flexible free-standing (PEI–CNT@PDA) film could be obtained by employing cellulose acetate (CA) as a sacrificial layer. The film could even withstand ultrasonication in saturated SDS aqueous solution for 30 min. SEM observations indicated that the ultrathin film consisted of nanoscale interpenetrating networks of entangled CNTs and exhibited a very rough surface morphology. The (PEI–CNT@PDA) film turned superhydrophobic after being coated with a low-surface-energy compound. The superhydrophobic films showed excellent resistance against the adhesion of both platelets and Escherichia coli (E. coli). The (PEI–CNT@PDA) films and the proposed methodology may find applications in the area of medical devices to reduce device-associated thrombosis and infection. [ABSTRACT FROM AUTHOR]

A pseudo-polycation was prepared based on the supramolecular cucurbit[8]uril ternary complex. It was then layer-by-layer assembled with poly(acrylic acid) to fabricate a stimuli-responsive film, which exhibited disassembly properties in response to stimuli, providing a supramolecular route for the fabrication of free-standing thin films. [ABSTRACT FROM AUTHOR]

The development of broad-spectrum anti-bacterial tough hydrogels without antibiotics remains a challenge in biomedical applications. In this study, we have synthesized a novel tough anti-bacterial complex hydrogel based on Cu 2+ coordination. A swollen and weak poly(acrylamide- co -4-vinylbenzyl-(trihydroxymethyl-phosphonium)chloride) (P(AAm- co -VBzTHPC)) hydrogel was prepared by the radical copolymerization of AAm and VBzTHPC monomer solutions, followed by immersion in CuSO 4 solution to coordinate with Cu 2+ to form a strong and tough hydrogel. Fourier transform infrared (FTIR) spectra and X-ray photoelectron spectra (XPS) were used to characterize the coordination structure between phosphorus and oxygen atoms in the VBzTHPC monomer and copper ions. The water content and mechanical properties of the obtained hydrogel varied with gel composition. The prepared toughened hydrogel exhibited excellent anti-bacterial performance because of the introduction of copper ion coordination and the slow release of copper ions, with bacterial viability of 5.1% when the mole fraction of VBzTHPC was 10 mol%. Cell viability when cocultured with the toughened hydrogel was above 85% using the Cell Counting Kit-8 (CCK-8) method, indicating the good biocompatibility of the hydrogel. Compared with the control group experiment in vivo , this tough hydrogel can also promote wound healing, making it a promising candidate for wound dressing.

The development of gene therapy puts forward the requirements for efficient delivery of genetic information into diverse cells. However, in some cases of transfection, especially those for transfecting some primary cells and for delivering large size plasmid DNA (pDNA), the existing conventional transfection methods show poor efficiency. How to further improve transfection efficiency in these hard-to-achieve issues remains a crucial challenge. Here, we report a photothermal-assisted surface-mediated gene delivery based on a polydopamine-polyethylenimine (PDA-PEI) surface. The PDA-PEI surface was prepared through PEI-accelerated dopamine polymerization, which showed efficiency in the immobilization of PEI/pDNA polyplexes and remarkable photothermal properties. Upon IR irradiation, we observed improved transfection efficiencies of two important hard-to-achieve transfection issues, namely the transfection of primary endothelial cells, which are kinds of typical hard-to-transfect cells, and the transfection of cells with large-size pDNA. We demonstrate that the increases of transfection efficiency were due to the hyperthermia-induced pDNA release, the local cell membrane disturbance, and the polyplex internalization. This work highlights the importance of local immobilization and release of pDNA to gene deliveries, showing great potential applications in medical devices in the field of gene therapy.