Understanding the Coupling Mechanism of Intercalation and Conversion Hybrid Storage in Lithium-Graphite Anode.

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.

Controlling Structural Transformation of Polyelectrolyte Films for Spatially Encapsulating Functional Species.

Although many approaches have been developed to encapsulate functional species into polyelectrolyte films, few of them can effectively control the final distribution of these ones. Herein, a facile strategy is proposed to spatially control the encapsulation of guest species by locally regulating the structural transformation of polyelectrolyte films. Patterned porosity is created within a film by cross-linking it selectively and then immersing it in an acidic solution. These porous regions can exhibit significantly different properties from other regions, including the ability to wick solution, a greater retention of guest species, and the capability of structural transformation. After loading guest species, the porous structures can be eliminated at saturated humidity to encapsulate the guest species into the film, leading to their patterned distribution across the film. Based on this method, various guest species, ranging from fluorescent dyes to nanoparticles, can be locally encapsulated into polyelectrolyte film, forming distinct patterns of arbitrary shapes and sizes and thus paving the way for further applications.

Substrate Stiffness Combined with Hepatocyte Growth Factor Modulates Endothelial Cell Behavior.

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.

Self-wrinkling polyelectrolyte multilayers: construction, smoothing and the underlying mechanism.

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.

Effect of Polyelectrolyte Film Stiffness on Endothelial Cells During Endothelial-to-Mesenchymal Transition.

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 ß1 (TGF-ß1), 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.

Facile fabrication of robust superhydrophobic multilayered film based on bioinspired poly(dopamine)-modified carbon nanotubes.

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.

Robust, Sprayable, and Multifunctional Hydrogel Coating through a Polycation Reinforced (PCR) Surface Bridging Strategy.

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.

Recent Developments in Layer-by-Layer Assembly for Drug Delivery and Tissue Engineering Applications.

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and for controlling biological processes. The layer-by-layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists of assembling complementary polyelectrolytes or biomolecules in a stepwise manner to form thin self-assembled films. In view of its simplicity, compatibility with biological molecules, and adaptability to any kind of supporting material carrier, this technology has undergone major developments over the past decades. Specific applications have emerged in different biomedical fields owing to the possibility to load or immobilize biomolecules with preserved bioactivity, to use an extremely broad range of biomolecules and supporting carriers, and to modify the film's mechanical properties via crosslinking. In this review, the focus is on the recent developments regarding LbL films formed as 2D or 3D objects for applications in drug delivery and tissue engineering. Possible applications in the fields of vaccinology, 3D biomimetic tissue models, as well as bone and cardiovascular tissue engineering are highlighted. In addition, the most recent technological developments in the field of film construction, such as high-content liquid handling or machine learning, which are expected to open new perspectives in the future developments of LbL, are presented.

UV-Triggered Hydrogel Coating of the Double Network Polyelectrolytes for Enhanced Endothelialization.

The left atrial appendage (LAA) occluder is an important medical device for closing the LAA and preventing stroke. The device-related thrombus (DRT) prevents the implantation of the occluder in exerting the desired therapeutic effect, which is primarily caused by the delayed endothelialization of the occluder. Functional coatings are an effective strategy for accelerating the endothelialization of occluders. However, the occluder surface area is particularly large and structurally complex, and the device is subjected to a large shear friction in the sheath during implantation, which poses a significant challenge to the coating. Herein, a hydrogel coating by the in situ UV-triggered polymerization of double-network polyelectrolytes is reported. The findings reveal that the double network and electrostatic interactions between the networks resulted in excellent mechanical properties of the hydrogel coating. The sulfonate and Arg-Gly-Asp (RGD) groups in the coating promoted hemocompatibility and endothelial growth of the occluder, respectively. The coating significantly accelerated the endothelialization of the LAA occluder in a canine model is further demonstrated. This study has potential clinical benefits in reducing both the incidence of DRT and the postoperative anticoagulant course for LAA closure.

Construction of redox-active multilayer film for electrochemically controlled release.

An electrochemically controlled drug release from a redox-active multilayer film is reported. The multilayer film is fabricated by alternate assembly of the electrochemical redox-active micelles and DNA. The buildup of multilayer films is monitored by spectroscopic ellipsometry, UV-vis spectroscopy, and fluorescence spectroscopy. A ferrocene-modified poly (ethyleneimine) (PEI-Fc) is used to form a hydrophobic ferrocene core and hydrophilic PEI shell micelle, showing the electrochemical redox-active properties. Hydrophobic pyrene (Py) molecules are then incorporated into the micelles. The PEI-Fc@Py micelles are assembled into the (PEI-Fc@Py/DNA) multilayer film by layer-by-layer assembly. Thanks to ferrocene groups with the properties of the hydrophilic-to-hydrophobic switch based on the electrical potential trigger, pyrene molecules can be control released from the multilayer film. The electrochemically controlled release of pyrene is investigated and confirmed by electrochemical quartz crystal microbalance and electrochemistry workstation. The (PEI-Fc@drug/DNA) multilayer film may have potential applications in the field of biomedical and nanoscale devices.

Cucurbit[8]uril supramolecular assembly for positively charged ultrathin films as nanocontainers.

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.

Silane coupling agent in biomedical materials.

Medical devices are becoming more and more significant in our daily life. For implantable medical devices, good biocompatibility is required for further use in vivo. Thus, surface modification of medical devices is really important, which gives a wide application scene for a silane coupling agent. The silane coupling agent is able to form a durable bond between organic and inorganic materials. The dehydration process provides linking sites to achieve condensation of two hydroxyl groups. The forming covalent bond brings excellent mechanical properties among different surfaces. Indeed, the silane coupling agent is a popular component in surface modification. Metals, proteins, and hydrogels are using silane coupling agent to link parts commonly. The mild reaction environment also brings advantages for the spread of the silane coupling agent. In this review, we summarize two main methods of using the silane coupling agent. One is acting as a crosslinker mixed in the whole system, and the other is to provide a bridge between different surfaces. Moreover, we introduce their applications in biomedical devices.

"Spongy skin" as a robust strategy to deliver 4-octyl itaconate for conducting dual-regulation against in-stent restenosis.

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 âˆ¼ 5.1). We further demonstrated that OI at a concentration of 25 µg/mL showed significant suppression of the TGF-ß/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.

Mechanical Enhancement of the Gelatin/Poly(zinc acrylate) Hydrogel Stent in Bile.

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 Cu2+ and Zn2+, have achieved a significant reinforcement of the mechanical strength of the hydrogels. Herein, we report a Zn2+-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 Ca2+ 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.

A pDNA/rapamycin nanocomposite coating on interventional balloons for inhibiting neointimal hyperplasia.

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.

Label-Free and In Situ Identification of Cells via Combinational Machine Learning Models.

Cell identification and counting in living and coculture systems are crucial in cell interaction studies, but current methods primarily rely on complicated and time-consuming staining techniques. Here, a label-free method to precisely recognize, identify, and instantly count cells in situ in coculture systems via combinational machine learning models s presented. A convolutional neural network (CNN) model is first used to generate virtual images of cell nuclei based on unlabeled phase-contrast images. Coordinates of all the cells are then returned according to the virtual nucleus images using two clustering algorithms. Finally, phase-contrast images of single cells are cropped based on the coordinates and sent into another CNN model for cell-type identification. This combinational approach is highly automatic and efficient, which requires few to no manual annotations of images in the training phase. It shows practical performance in different cell culture conditions including cell ratios, densities, and substrate materials, having great potential in real-time cell tracking and analyzing.

The substrate stiffness at physiological range significantly modulates vascular cell behavior.

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.

Bioinspired NO release coating enhances endothelial cells and inhibits smooth muscle cells.

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.

Tough complex hydrogels transformed from highly swollen polyelectrolyte hydrogels based on Cu2+ coordination with anti-bacterial properties.

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.

Mir-22-incorporated polyelectrolyte coating prevents intima hyperplasia after balloon-induced vascular injury.

Drug-coated balloons (DCBs) offer potential to deliver drugs to treat coronary lesions but without leaving permanent implants behind. Paclitaxel and sirolimus are anti-proliferation drugs that are commonly used in commercially available DCBs. However, these drugs present significant cytotoxicity concern and low efficacy in vivo. Here, we use microRNA-22 (miR-22) as balloon loaded drugs and polyelectrolyte complexes (PECs) polyethyleneimine/polyacrylic acid (PEI/PAA) as balloon coatings to establish a new DCB system through the ultrasonic spray method. The PEI/PAA forms a stable and thin coating on the balloon, which resulted in a good transfer capacity to the vessel wall both in vitro and in vivo. miR-22 that could modulate smooth muscle cell (SMC) phenotype switching is incorporated into the PEI/PAA coating and shows a sustained release profile. The PEI/PAA/miR-22 coated balloon successfully inhibits intima hyperplasia after balloon-induced vascular injury in a rat model through decreasing proliferative SMCs via the miR-22-methyl-CpG binding protein 2 (MECP2) axis. Our findings indicate that balloons coated with PEI/PAA/miR-22 have great potential to be promising DCBs in the treatment of cardiovascular disease.