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Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 430-439, 2015. [ABSTRACT FROM AUTHOR]

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]

The valid management of inflammation and precise inhibition of smooth muscle cells (SMCs) is regarded as a promising strategy for regulating vascular responses after stent implantation, yet posing huge challenges to current coating constructions. Herein, we proposed a spongy cardiovascular stent for the protective delivery of 4-octyl itaconate (OI) based on a "spongy skin" approach, and revealed the dual-regulation effects of OI for improving vascular remolding. We first constructed a "spongy skin" onto poly-l-lactic acid (PLLA) substrates, and realized the protective loading of OI with the highest dosage of 47.9 μg/cm2. Then, we verified the remarkable inflammation mediation of OI, and surprisingly revealed that the OI incorporation specifically inhibited SMC proliferation and phenotype switching, which contributed to the competitive growth of endothelial cells (EC/SMC ratio ∼ 5.1). We further demonstrated that OI at a concentration of 25 μg/mL showed significant suppression of the TGF-β/Smad pathway of SMCs, leading to the promotion of contractile phenotype and reduction of extracellular matrix. In vivo evaluation indicated that the successful delivery of OI fulfilled the inflammation regulation and SMCs inhibition, therefore suppressing the in-stent restenosis. This "spongy skin" based OI eluting system may serve as a new strategy for improving vascular remolding, and provides a potential concept for the treatment of cardiovascular diseases. "Spongy skin" was constructed on PLLA stents to protectively deliver 4-octyl itaconate (OI) for improving vascular remolding. The OI-eluting stent showed a dual-regulation effect including the remarkable regulation of inflammation and suppression of SMCs proliferation, therefore realizing the inhibition of in-stent restenosis. This "spongy skin" based OI-eluting system provides a potential concept for the treatment of cardiovascular diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

A coating of implanted medical devices with antifouling ability, preferable mechanical property and stability in the physiological environment proves beneficial for their clinical use. Here we develop a flexible bilayer hydrogel coating with self-healing, antifouling, and lubricating functions. Our bilayer coating consists of two functional layers: i) an adhesive flexible polyelectrolyte hydrogel layer, ii) an antifouling and lubricous polyzwitterionic layer. The bilayer hydrogel coating is prepared in two steps dip-coating and in situ UV photopolymerization. Our results demonstrate that the prepared bilayer hydrogel coating has proper mechanical properties, favorable hydrophilicity, and lower surface friction. We demonstrate that the bilayer hydrogel coating maintains hydrophilicity under extreme condition (1 h sonicating or 5000 times repeating bending). The as-prepared bilayer hydrogel coating resists non-specific protein adsorption, inhibits cell and platelet adhesion, and prevents thrombosis. This work provides a reliable coating on the medical materials, showing a promising practical application in diversified implantable medical devices. [Display omitted] [ABSTRACT FROM AUTHOR]

Changes in the stiffness of the cellular microenvironment are involved in many pathological processes of blood vessels. Substrate stiffness has been shown to have extensive effects on vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). However, the material stiffness of most previously reported in-vitro models is ranging from ~100 kPa to the magnitude of MPa, which does not match the mechanical properties of natural vascular tissue (10–100 kPa). Herein, we constructed hydrogel substrates with the stiffness of 18–86 kPa to explore the effect of physiological stiffness on vascular cells. Our findings show that, with the increase of stiffness at the physiological range, the cell adhesion and proliferation behaviors of VECs and VSMCs are significantly enhanced. On the soft substrate, VECs express more nitric oxide (NO), and VSMCs tend to maintain a healthy contraction phenotype. More importantly, we find that the number of differentially expressed genes in cells cultured between 18 kPa and 86 kPa substrates (560 in VECs, 243 in VSMCs) is significantly higher than that between 86 kPa and 333 kPa (137 in VECs, 172 in VSMCs), indicating that a small increase in stiffness within the physiological range have a higher impact on vascular cell behaviors. Overall, our results expanded the exploration of how stiffness affects the behavior of vascular cells at the physiological range. [Display omitted] • Changes in the stiffness of a material at the physiological range have a stronger effect on the vascular cells. • Materials stiffness affects endothelial cell adhesion and function • Smooth muscle cell proliferation and phenotype are affected by materials stiffness. [ABSTRACT FROM AUTHOR]

Dendrite growth of lithium (Li) metal anodes is considered as one of the most tough issues for Li metal batteries with a theoretically high energy density. This is attributed to the rapid exhaustion of Li ions at the electrode/electrolyte interface, which is even worse at low temperatures with poor diffusion kinetics of Li ions. Here, pulse charge with intermittent rest time during battery charging is proposed to handle the dendrite growth issue of Li metal anodes at low temperatures. The depleted Li ions near the interfaces can be rapidly replenished during the rest time, thus effectively suppressing the dendrites growth. Further investigations indicate that the large dendrites can be suppressed at the Li ion nucleation stage. The equivalent lifespan considering the rest time is proposed. At -10oC, the lifespan of Li||Li batteries cycled under 3 mA cm-2 and 1 mAh cm-2 is increased from 24 h to equivalent 64 h. Li ||LiNi0.5Co0.2Mn0.3O2 batteries with 80% capacity retention can be stably operated from 39 cycles to 56 cycles. This design presents an efficient and convenient strategy to regulate the deposition behaviors of Li metal anodes with a dendrite-free morphology., (© 2024 Wiley‐VCH GmbH.)

Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g -1 , its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries., (© 2024 Wiley‐VCH GmbH.)

Hydrogels with the features of softness, biocompatibility, and modifiability have emerged as excellent materials in the biomedical field. However, the poor mechanical properties of the hydrogels limit their further practical applications. Double-network and metal ion coordination, such as Cu 2+ and Zn 2+ , have achieved a significant reinforcement of the mechanical strength of the hydrogels. Herein, we report a Zn 2+ -enhanced polyelectrolyte double-network hydrogel stent with a mechanical enhancement phenomenon in bile. The gelatin/poly(zinc acrylate) (PZA) stent was constructed by dip-coating and UV irradiation. Although the mechanical strength of the as-prepared stent was quite weak, it was discovered to be mechanically enhanced by the natural bile. After exploring the effect of different components on the stents according to the components of bile, we found that Ca 2+ in bile made a contribution to the mechanical enhancement of the stent. It is envisioned that this bile-enhanced gelatin/PZA stent provides a train of thought for the potential application of hydrogels in the biliary environment.

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.

Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis, angiosteosis, and vascular aging. Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell. Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering, regenerative medicine, and medical devices. Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells (VECs) and smooth muscle cells (VSMCs). Interestingly, our findings demonstrate that, with the increase of substrate stiffness, the autophagy level of VECs and VSMCs showed differential changes: endothelial autophagy levels reduced, leading to the reductions in a range of gene expression associated with endothelial function; while, autophagy levels of VSMCs increased, showing a transition from contractile to the synthetic phenotype. We further demonstrate that, by inhibiting cell autophagy, the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased, suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing. Although the underlying mechanism requires further study, this work highlights the relationship of substrate stiffness, autophagy, and vascular cell behaviors, and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (© 2020 [The Author/The Authors].)

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.