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.

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.

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.

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.

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.

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.

"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.

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.

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.

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.

Fabrication of "Spongy Skin" on Diversified Materials Based on Surface Swelling Non-Solvent-Induced Phase Separation.

Porous surfaces have attracted tremendous interest for customized incorporation of functional agents on biomedical devices. However, the versatile preparation of porous structures on complicated devices remains challenging. Herein, we proposed a simple and robust method to fabricate "spongy skin" on diversified polymeric substrates based on non-solvent-induced phase separation (NIPS). Through the swelling and the subsequent phase separation process, interconnected porous structures were directly formed onto the polymeric substrates. The thickness and pore size could be regulated in the ranges of 5-200 and 0.3-0.75 µm, respectively. The fast capillary action of the porous structure enabled controllable loading and sustained release of ofloxacin and bovine albumin at a high loading dosage of 79.9 and 24.1 µg/cm2, respectively. We verified that this method was applicable to diversified materials including polymethyl methacrylate, polystyrene, thermoplastic polyurethane, polylactide acid, and poly(lactic-co-glycolic acid) and can be realized onto TCPS cell culture plates. This NIPS-based method is promising to generate porous surfaces on medical devices for incorporating therapeutic agents.

A Bioinspired Hydrogel-Elastomer Hybrid Surface for Enhanced Mechanical Properties and Lubrication.

Developing surfaces that realize lubrication and durable wear resistance under high pressure has great implications in areas ranging from electromechanical systems to advanced biomedical devices but has proven challenging. Inspired by the zonal and transitional structure of articular cartilage, we fabricate a hydrogel-elastomer hybrid surface, where the hydrogel interpenetrates into the polymer elastomer substrate as a transitional and bonding zone, that exhibits a low coefficient of friction and wear resistance under a high load. First, we entrap benzophenone within the surface of polymer substrates such as polydimethylsiloxane, polyvinylchloride, and polyurethane. The hybrid surface is then achieved through initiating polymerization of the acrylamide monomer on the polymer surface upon ultraviolet irradiation. We observe an interpenetration area of the hydrogel and the polymer substrate. The hybrid surface shows a low coefficient of friction (∼0.05) under a very high load (over 100 atm contact pressure). It conserves the lubrication property over 100,000 cycles under a 10.9 MPa pressure and shows slight wear. This work brings a new perspective on designing surfaces with a lubrication property and wear resistance, showing broad applications.

miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis.

The in-stent restenosis (IRS) after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation. MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells (EC) and smooth muscle cells (SMC) in response to vascular injury, providing a promising therapeutic candidate to inhibit IRS. However, the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings. Here, we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) triblock copolymer spongy network. The miR-22 was used as a model microRNA to regulate SMC. The dynamic porous coating realized the uniform and controllable loading of miR-22, reaching the highest dosage of 133 pmol cm-2. We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC, thus leading to the EC dominating growth at an EC/SMC ratio of 5.4. More importantly, the PCEC@miR-22 coated stents showed reduced inflammation, low switching of SMC phenotype, and low secretion of extracellular matrix, which significantly inhibited IRS. This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent, which may extend to other combination medical devices, and facilitate practical application of bioactive agents in clinics.

Periodic Stratified Porous Structures in Dynamic Polyelectrolyte Films Through Standing-Wave Optical Crosslinking for Structural Color.

Periodic porous structures have been introduced into functional films to meet the requirements of various applications. Though many approaches have been developed to generate desired structures in polymeric films, few of them can effectively and dynamically achieve periodic porous structures. Here, a facile way is proposed to introduce periodic stratified porous structures into polyelectrolyte films. A photo-crosslinkable polyelectrolyte film of poly(ethylenimine) (PEI) and photoreactive poly(acrylic acid) derivative (PAA-N3 ) is prepared by layer-by-layer (LbL) self-assembly. Stratified crosslinking of the PEI/PAA-N3 film is generated basing on standing-wave optics. The periodic stratified porous structure is constructed by forming pores in noncrosslinked regions in the film. Thanks to the dynamic mobility of polyelectrolytes, this structural controlment can be repeated several times. The size of pores corresponding to the layer spacing of the film contributes to the structural colors. Furthermore, structural color patterns are fabricated in the film by selective photo-crosslinking using photomasks. Although the large-scale structural controlment in thick (micron-scale and above) films needs to be explored further, this work highlights the periodic structural controlment in polymeric films and thus presents an approach for application potentials in sensor, detection, and ink-free printing.

The influence of substrate stiffness on osteogenesis of vascular smooth muscle cells.

Vascular stiffening occurs with advanced age and under pathological conditions such as vascular calcification, during which the osteogenesis of smooth muscle cells (SMCs) plays a key role. However, whether the stiffness of cellular microenvironment influences osteogenic responses in vascular SMCs is not well understood. Here, we cultured SMCs on the poly(dimethylsiloxane) (PDMS) substrates with varying stiffness from 0.363 to 2.327 MPa. The cell osteogenic transdifferentiation was induced by ß-glycerophosphate. Our findings demonstrated that the extent of osteogenesis in SMCs varied with the substrate stiffness. On three substrate stiffness, cells on the intermediate one (0.909 MPa) showed the highest extent of the osteogenesis based on the expression of osteogenic markers and calcium deposition. Transforming growth factor-ß1 and autophagy were involved in this stiffness-dependent process. This work highlights the importance of substrate stiffness to the osteogenesis of vascular SMCs, giving new scientific information for understanding of SMCs-mediated vascular calcification and designing of vascular implants.

Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells.

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.

Reversibly Transforming a Highly Swollen Polyelectrolyte Hydrogel to an Extremely Tough One and its Application as a Tubular Grasper.

Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) and its copolymer hydrogels are typical polyelectrolyte gels with extremely high swelling capacity that are widely used in industry. It's common to consider these hydrogels as weak materials that are difficult to toughen. Reported here is a facile strategy to transform swollen and weak poly(acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid) [P(AAm-co-AMPS)] hydrogels to tough ones by forming strong sulfonate-Zr4+ metal-coordination complexes. The resultant hydrogels with moderate water content possess high stiffness, strength, and fracture energy, which can be tuned over 3-4 orders of magnitude by controlling the composition and metal-to-ligand ratio. Owing to the dynamic nature of the coordination bonds, these hydrogels show rate- and temperature-dependent mechanical performances, as well as good self-recovery properties. This strategy is universal, as manifested by the drastically improved mechanical properties of hydrogels of various natural and synthetic sulfonate-containing polymers. The toughened hydrogels can be converted to the original swollen ones by breaking up the metal-coordination complexes in alkaline solutions. The reversible brittle-tough transition and concomitant dramatic volume change of polyelectrolyte hydrogels afford diverse applications, as demonstrated by the design of a tubular grasper with holding force a thousand times its own weight for objects with different geometries. It is envisioned that these hydrogels enable versatile applications in the biomedical and engineering fields.