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Anelectrochemically controlled drug release from a redox-activemultilayer film is reported. The multilayer film is fabricated byalternate assembly of the electrochemical redox-active micelles andDNA. The buildup of multilayer films is monitored by spectroscopicellipsometry, UV–vis spectroscopy, and fluorescence spectroscopy.A ferrocene-modified poly (ethyleneimine) (PEI-Fc) is used to forma hydrophobic ferrocene core and hydrophilic PEI shell micelle, showingthe electrochemical redox-active properties. Hydrophobic pyrene (Py)molecules are then incorporated into the micelles. The PEI-Fc@Py micellesare assembled into the (PEI-Fc@Py/DNA) multilayer film by layer-by-layerassembly. Thanks to ferrocene groups with the properties of the hydrophilic-to-hydrophobicswitch based on the electrical potential trigger, pyrene moleculescan be control released from the multilayer film. The electrochemicallycontrolled release of pyrene is investigated and confirmed by electrochemicalquartz crystal microbalance and electrochemistry workstation. The(PEI-Fc@drug/DNA) multilayer film may have potential applicationsin the field of biomedical and nanoscale devices. [ABSTRACT FROM AUTHOR]

Surface-mediated gene delivery appears to be potential gene delivery modes for various applications. Still, controlled and smart delivery manners are required especially considering the need for gene therapy to deliver gene with selectivity. A surface that can effectively payload DNA, promote cell adhesion, and stimuli response is an important prerequisite. Here, we report a matrix metalloproteinase (MMP)-responsive surface-mediated gene delivery system by combining MMP-degradable hydrogel with a breath figure (BF) porous film. The MMP-degradable hydrogel containing plasmid DNA was loaded into the surface pores of the BF film as DNA reservoirs. The upper surface without hydrogel on the BF film served as footholds of integrin adhesions. MMP is one of the important endogenous signals in tumor-related pathologic changes, and MMP expressions in cancer cells are significantly higher than those in normal cells. Consequently, our surface-mediated gene delivery locally and rapidly released the payload DNA in response to cancer cells and transfected them. This work highlights the importance of the combination of stimuli-response and surface-mediated gene delivery to functional materials, showing good potential applications in the field of gene therapy.

Spatially controlling the evolution of surface structures may provide an effective strategy for patterning surface roughness and facilitating the construction of various functional surfaces. In this study, we report a photo-cross-linkable polymeric film with dynamic surface micro/nanostructures. The surface structures of the un-cross-linked regions can be eliminated under saturated humidity, which can be utilized to create patterned roughness on the film. One potential application of this patternable platform is as a "smart" label material for graphical symbols. Various graphical symbols can be programmed onto this film by partially erasing its surface roughness, enabling visibility due to the difference in light scattering between different areas of the film. When a thus-prepared label was blurred by mechanical scratches, it could be healed under saturated humidity, and its original readability could be fully restored. Furthermore, the patterned rough surface created using our approach can also be very useful in many other research fields, such as surface wettability and cell behavior manipulation.

Achievement of an endothelial cell (EC) monolayer (re-endothelialization) on the vascular implant surface with competent and functioning features is critical for long-term safety after implantation. Oriented EC monolayer is beneficial to improve endothelial function such as enhanced athero-resistant property. However, the information about antithrombotic property of oriented EC monolayer is limited. Here, we used the microgrooved polydimethylsiloxane substrates to guide EC orientation and obtain oriented EC monolayer. The effects of anisotropic topography on EC behaviors and antithrombotic function of the EC monolayer were then evaluated. Our data demonstrated that ECs responded to grooves in a size-dependent way as shown in oriented cell cytoskeleton and nuclei, enhanced directed migration, and overall velocity. Furthermore, compared to the EC monolayer on the flat surface, the oriented EC monolayer formed on the grooved substrates exhibited improved antithrombotic capability as indicated by higher expression of functional related genes, production of prostacyclin and tissue plasminogen activator, and prolonged activated coagulation time. The improvement of antithrombotic function was especially notable on the smaller-size groove. These findings reveal the responses of ECs to varisized topography and antithrombotic function of the oriented EC monolayer, providing insights into optimal design of vascular implants.

Cationic antibacterial coating based on quaternary ammonium compounds, with an efficient and broad spectrum bactericidal property, has been widely used in various fields. However, the high density of positive charges tends to induce weak hemocompatibility, which hinders the application of the cationic antibacterial coating in blood-contacting devices and implants. It has been reported that a negatively charged surface can reduce blood coagulation, showing improved hemocompatibility. Here, we describe a strategy to combine the cationic and anionic groups by using mixed-charged copolymers. The copolymers of poly (quaternized vinyl pyridine- co- n-butyl methacrylate- co-methacrylate acid) [P(QVP- co- nBMA- co-MAA)] were synthesized through free radical copolymerization. The cationic group of QVP, the anionic group of MAA, and the hydrophobic group of nBMA were designed to provide bactericidal capability, hemocompatibility, and coating stability, respectively. Our findings show that the hydrophilicity of the copolymer coating increased, and its zeta potential decreased from positive charge to negative charge with the increase of the anionic/cationic ratio. Meanwhile, the bactericidal property of the copolymer coating was kept around a similar level compared with the pure quaternary ammonium copolymer coating. Furthermore, the coagulation time, platelet adhesion, and hemolysis tests revealed that the hemocompatibility of the copolymer coating improved with the addition of the anionic group. The mixed-charged copolymer combined both bactericidal property and hemocompatibility and has a promising potential in blood-contacting antibacterial devices and implants.

Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C 10 -COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C 10 -N 4 ). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.

Introducing a lubricant layer onto surfaces has emerged as a novel strategy to address a wide range of interface-related challenges. Recent studies of lubricant-infused surfaces have extended beyond repelling liquids to manipulating the mobility of fluids. In this study, we report a design of slippery surfaces based on infusing lubricant onto a polyelectrolyte multilayer film whose surface microstructures can be erased rapidly under mild condition. Unlike other lubricant-infused surfaces, the liquid movements (e.g., moving resistance and direction) on such surfaces can be manipulated via programming the surface microstructures beforehand. The work reported here offers a versatile design concept of lubricant-infused surfaces and may turn on new applications of this emerging class of bioinspired materials.

Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC-based regenerative medicine.

Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.

Optimized ratio in the codelivery of therapeutics is of crucial importance to promote the synergism rather than the antagonistic effects. In this study, a self-healing spongy coating was described to facilitate the surface-mediated delivery of drug "cocktails" proportionally. The formation of spongy structures within the coating was achieved by acidic treatment and freeze-drying. Various drug combinations can be readily integrated through wicking method and subsequent micropore self-healing. The ratio of drug loading can be precisely regulated by the composition of loading solution and the embedded drugs were released in proportion according to the initial ratio of drug combination.

Endothelial-to-mesenchymal transition (EndMT), during which endothelial cells (ECs) transdifferentiate into mesenchymal phenotype, plays a key role in the development of vascular implant complications such as endothelium dysfunction and in-stent restenosis. Substrate stiffness has been confirmed as a key factor to influence EC behaviors; however, so far, the relationship between substrate stiffness and EndMT has been rarely studied. Here, ECs were cultured on the (poly(L-lysine)/hyaluronate acid) (PLL/HA) multilayer films with controlled stiffness for 2 weeks, and their EndMT behaviors were studied. We demonstrated that ECs lost their markers (vWf and CD31) in a stiffness-dependent manner even without supplement of growth factors, and the softer film favored the maintaining of EC phenotype. Further, induced by transforming growth factor β1 (TGF-β1), ECs underwent EndMT, as characterized by losing their typical cobblestone morphology and markers and gaining smooth muscle cell markers (α-smooth muscle actin and calponin). Interestingly, stronger EndMT was observed when ECs were cultured on the stiffer film. Collectively, our findings suggest that substrate stiffness has significant effects on EndMT, and a softer substrate is beneficial to ECs by keeping their phenotype and inhibiting EndMT, which presents a new strategy for surface design of vascular implant materials.

The design of positively charged ultrathin films for surface modification is of crucial importance for biomedical applications. Herein, we report the layer-by-layer assembly of pure positively charged ultrathin films based on the host-guest interaction of cucurbit[8]uril (CB[8]). Two positively charged poly(ethylenimine)s (PEI) functionalized with guest moieties methyl viologen (MV) and indole (ID) were alternately assembled with the formation of CB[8] ternary complex under basic conditions. The growth of the (PEI-MV@CB[8]/PEI-ID) films was monitored by spectroscopic ellipsometry and quartz crystal microbalance. The morphology and structure of the films were characterized by scanning electron microscopy and UV-vis spectroscopy, respectively. These positively charged (PEI-MV@CB[8]/PEI-ID) films were very stable in the pH range from 4 to 9 but disassembled immediately when subjected to a competitive guest adamantylamine. Finally, the films were successfully employed as nanocontainers for DNA loading and subsequent directing the transfection of the adhered cells.

Infections associated with medical devices have become a major concern. The adhesion of bacteria to the devices' surfaces during the initial 24 h is believed to be a "decisive period" for implant-associated infections, which pose key challenges to optimal antiadhesion of microbes in this period. Herein, we have designed and constructed a (heparin/chitosan)10-(polyvinylpyrrolidone/poly(acrylic acid))10 [(HEP/CHI)10-(PVP/PAA)10] multilayer film by layer-by-layer self-assembly. Assembly of the underlying (HEP/CHI)10 multilayer film is based on electrostatic interactions, showing the properties of contact killing of bacteria. Deposition of the top (PVP/PAA)10 multilayer film is based on hydrogen bond interactions. The PAA molecules are then cross-linked to form anhydride groups by thermal treatment at 110 °C for 16 h. Therefore, it shows a top-down degradable capability in the determined period, leading to almost no adhesion of bacteria in 24 h. Our system combining the adhesion resistance and the contact killing properties shows an enhanced antibacterial capability through targeting the "decisive period" of implantation may have great potential for applications in medical implants, tissue engineering, etc.