A Near-Infrared Photothermal-Responsive Underwater Adhesive with Tough Adhesion and Antibacterial Properties.

Developing tunable underwater adhesives that possess tough adhesion in service and easy detachment when required remains challenging. Herein, a strategy is proposed to design a near infrared (NIR) photothermal-responsive underwater adhesive by incorporating MXene (Ti3 C2 Tx )-based nanoparticles within isocyanate-modified polydimethylsiloxane (PDMS) polymer chains. The developed adhesive exhibits long-term and tough adhesion with an underwater adhesion strength reaching 5.478 MPa. Such strong adhesion is mainly attributed to the covalent bonds and hydrogen bonds at the adhesive-substrate interface. By making use of the photothermal-response of MXene-based nanoparticles and the thermal response of PDMS-based chains, the adhesive possesses photothermal-responsive performance, exhibiting sharply diminished adhesion under NIR irradiation. Such NIR-triggered tunable adhesion allows for easy and active detachment of the adhesive when needed. Moreover, the underwater adhesive exhibits photothermal antibacterial property, making it highly desirable for underwater applications. This work enhances the understanding of photothermal-responsive underwater adhesion, enabling the design of tunable underwater adhesives for biomedical and engineering applications.

Hydro-Sensitive, In Situ Ultrafast Physical Self-Gelatinizing, and Red Blood Cells Strengthened Hemostatic Adhesive Powder with Antibiosis and Immunoregulation for Wound Repair.

Immediate and effective hemostatic treatments for complex bleeding wounds are an urgent clinical demand. Hemostatic materials with characteristics of adhesion, sealing, anti-infection, and concrescence promotion have drawn growing concerns. However, pure natural multifunctional hemostatic materials with in situ ultrafast self-gelation are rarely reported. In this study, a hydro-sensitive collagen/tannic acid (ColTA) natural hemostatic powder is developed that can in situ self-gel to form adhesive by the non-covalent crosslinking between tannic acid (TA) and collagen (Col) in liquids. The physical interactions endow ColTA adhesive with the characteristics of instantaneous formation and high adhesion at various substrate surfaces. Crucially, ColTA powder adhesive shows an enhanced adhesion performance in the presence of blood due to the electrostatic interactions between ColTA adhesive and red blood cells, conducive to effective in situ sealing and rapid hemostasis. The biocompatible and hemocompatible ColTA adhesive can effectively control bleeding and seal the wounds of the caudal vein, liver, heart, and femoral arteries in rats. Furthermore, the low-cost and ready-to-use ColTA adhesive powder also possesses good antibacterial and inhibiting biofilm formation ability, and can efficiently regulate immune response by the NF-κB pathway to promote wound repair, making it a highly promising hemostatic material with great potential for biomedical applications.

Cartilage-Inspired Inhomogeneous Salt-Hydrogel for Hydrated Drag-Reducing and Strain Sensing.

Articular cartilages exhibit load-bearing capacity and durability due to their inhomogeneous structure. Inspired by this unique structure, a tough and inhomogeneous salt-hydrogel was developed by trapping sodium acetate (NaAc) crystals in polyacrylamide (PAM) polymer networks and then partially redissolving the NaAc crystals. The compressive and tensile stresses of the salt-hydrogel increase significantly by more than 20 times when oversaturated Ac- and Na+ are introduced into the gel network. Such an enhancement in mechanical strength is primarily attributed to the formation of NaAc crystals within the gel network. Further investigations reveal that the mechanical strength of the salt-hydrogel is temperature-dependent as the NaAc crystals gradually redissolve in the gel network with increasing temperature. Furthermore, redissolving NaAc crystals in an aqueous solution can yield an inhomogeneous salt-hydrogel. The topmost soft surface of the salt-hydrogel offers hydration lubrication, while the inhomogeneous network confers load-bearing capacity and durability. Compared to regular hydrogels, the inhomogeneous salt-hydrogel surface can realize drag reduction and remain smooth without damage after the friction tests. Moreover, a salt-hydrogel coating is also fabricated to visually demonstrate its drag-reducing property. In addition, this salt-hydrogel possesses conductivity and can be utilized in the development of inhomogeneous salt-hydrogel fibers (diameter = 438 ± 7 µm) for strain detection. The produced salt-hydrogel fiber exhibits excellent durability and reproducibility as a strain sensor, capable of detecting both small strains (e.g., 1%) and large strains (e.g., 40%). This work provides fundamental insights into developing hydrogels with an inhomogeneous network and explores their potential applications (e.g., hydrated drag-reducing, strain sensing).

Kneading-Dough-Inspired Quickly Dispersing of Hydrophobic Particles into Aqueous Solutions for Designing Functional Hydrogels.

Hydrogels containing hydrophobic materials have attracted great attention for their potential applications in drug delivery and biosensors. This work presents a kneading-dough-inspired method for dispersing hydrophobic particles (HPs) into water. The kneading process can quickly mix HPs with polyethyleneimine (PEI) polymer solution to form "dough", which facilitates the formation of stable suspensions in aqueous solutions. Combining with photo or thermal curing processes, one type of HPs incorporated PEI-polyacrylamide (PEI/PAM) composite hydrogel exhibiting good self-healing ability, tunable mechanical property is synthesized. The incorporating of HPs into the gel network results in the decrease in the swelling ratio, as well as the enhancement of the compressive modulus by more than five times. Moreover, the stable mechanism of polyethyleneimine-modified particles has been investigated using surface force apparatus, where the pure repulsion during approaching contributes to the good stability of the suspension. The stabilization time of the suspension is dependent on the molecular weight of PEI: the higher the molecular weight is, the better the stability of the suspension will be. Overall, this work demonstrates a useful strategy to introduce HPs into functional hydrogel networks. Future research can be focused on understanding the strengthening mechanism of HPs in the gel networks.

Two-step method fabricating a 3D nerve cell model with brain-like mechanical properties and tunable porosity vascular structures via coaxial printing.

Three-dimensional (3D) nerve cell models have been widely developed to understand the mechanisms and discover treatment methods of ischemic stroke and neurodegenerative disease. However, there is a contradiction in the production of 3D models that they should possess high modulus to ensure mechanical stability while low modulus to provide mechanical stimuli for nerve cells. In addition, it is challenging to maintain the long-term viability of 3D models when lacking vascular structures. Here, a 3D nerve cell model with brain-like mechanical properties and tunable porosity vascular structures has been fabricated. The matrix materials with brain-like low mechanical properties were favorable for promoting HT22 proliferation. The nerve cells could exchange nutrients and waste with the cultural environment through vascular structures. The vascular structures also played a supporting role, and model stability was enhanced by combining matrix materials with vascular structures. Furthermore, the porosity of vascular structure walls was adjusted by adding sacrificial materials to the tube walls during 3D coaxial printing and removing them after preparation, resulting in tunable porosity vascular structures. Finally, HT22 cells showed better cell viability and proliferation performance after culturing 7 days in the 3D models with vascular structures than in the 3D models with solid structures. All these results suggest that this 3D nerve cell model possesses good mechanical stability and long-term viability, which is expected to be used in pathological studies and drug screening for ischemic stroke and neurodegenerative diseases.

A multifunctional chitosan-based hydrogel with self-healing, antibacterial, and immunomodulatory effects as wound dressing.

Bacterial infection often leads to inflammatory responses and delays wound healing. Chitosan (CS)-based composite hydrogels can hold desirable mechanical properties and maintain excellent antibacterial abilities, and thus may be promising as wound dressings. Although CS-based hydrogels have been widely studied on the antibacterial and wound-healing abilities, their immunomodulatory abilities were rarely evaluated. Herein, we developed a multifunctional CS/Poly[2-(methacryloyloxy)ethyl] trimethyl ammonium chloride (PMETAC) hydrogel. In vitro, this hydrogel exhibited self-healing ability and excellent biocompatibility, promoted macrophage polarization towards M2 phenotype, and showed desirable antibacterial activity. In vivo, this hydrogel accelerated the wound regeneration process by reducing bacterial burden, increasing collagen deposition, stimulating angiogenesis, promoting macrophage polarization to M2 direction, and shifting the balance of T helper type 17 (Th17) cells towards anti-inflammatory regulatory T (Treg) cells. This work revealed the potential immunomodulatory effect of CS-based wound dressings and thus may provide a novel target for developing efficient wound healing tools.

A Deep-Learning-Based Guidewire Compliant Control Method for the Endovascular Surgery Robot.

Endovascular surgery is a high-risk operation with limited vision and intractable guidewires. At present, endovascular surgery robot (ESR) systems based on force feedback liberates surgeons' operation skills, but it lacks the ability to combine force perception with vision. In this study, a deep learning-based guidewire-compliant control method (GCCM) is proposed, which guides the robot to avoid surgical risks and improve the efficiency of guidewire operation. First, a deep learning-based model called GCCM-net is built to identify whether the guidewire tip collides with the vascular wall in real time. The experimental results in a vascular phantom show that the best accuracy of GCCM-net is 94.86 ± 0.31%. Second, a real-time operational risk classification method named GCCM-strategy is proposed. When the surgical risks occur, the GCCM-strategy uses the result of GCCM-net as damping and decreases the robot's running speed through virtual resistance. Compared with force sensors, the robot with GCCM-strategy can alleviate the problem of force position asynchrony caused by the long and soft guidewires in real-time. Experiments run by five guidewire operators show that the GCCM-strategy can reduce the average operating force by 44.0% and shorten the average operating time by 24.6%; therefore the combination of vision and force based on deep learning plays a positive role in improving the operation efficiency in ESR.

Manufacturing and post-engineering strategies of hydrogel actuators and sensors: From materials to interfaces.

Living bodies are made of numerous bio-sensors and actuators for perceiving external stimuli and making movement. Hydrogels have been considered as ideal candidates for manufacturing bio-sensors and actuators because of their excellent biocompatibility, similar mechanical and electrical properties to that of living organs. The key point of manufacturing hydrogel sensors/actuators is that the materials should not only possess excellent mechanical and electrical properties but also form effective interfacial connections with various substrates. Traditional hydrogel normally shows high electrical resistance (~ MΩ•cm) with limited mechanical strength (<1 MPa), and it is prone to fatigue fracture during continuous loading-unloading cycles. Just like iron should be toughened and hardened into steel, manufacturing and post-treatment processes are necessary for modifying hydrogels. Besides, advanced design and manufacturing strategies can build effective interfaces between sensors/actuators and other substrates, thus enhancing the desired mechanical and electrical performances. Although various literatures have reviewed the manufacture or modification of hydrogels, the summary regarding the post-treatment strategies and the creation of effective electrical and mechanically sustainable interfaces are still lacking. This paper aims at providing an overview of the following topics: (i) the manufacturing and post-engineering treatment of hydrogel sensors and actuators; (ii) the processes of creating sensor(actuator)-substrate interfaces; (iii) the development and innovation of hydrogel manufacturing and interface creation. In the first section, the manufacturing processes and the principles for post-engineering treatments are discussed, and some typical examples are also presented. In the second section, the studies of interfaces between hydrogels and various substrates are reviewed. Lastly, we summarize the current manufacturing processes of hydrogels, and provide potential perspectives for hydrogel manufacturing and post-treatment methods.

Ferroferric oxide loaded near-infrared triggered photothermal microneedle patch for controlled drug release.

HYPOTHESIS: The drug release efficiency of microneedle is usually slower than that of oral delivery or hypodermic injection, which severely restricts its widespread use. Herein, a Fe3O4-loaded photothermal microneedle (Fe3O4@MN) patch is developed for controlled drug delivery. Under near infrared (NIR) irradiation, the drug loaded on Fe3O4@MN can be quickly released, achieving an enhanced drug release efficiency. EXPERIMENTS: The mechanical property and characterization of Fe3O4@MN were systematically investigated, and the photothermal performance of Fe3O4@MN was also conducted. Moreover, the model-drug-releasing tests and doxycycline hydrochloride releasing tests were carried out to evaluate the drug release performance of Fe3O4@MN under NIR irradiation. FINDINGS: Fe3O4@MN has enough mechanical strength to pierce into skins, and the temperature of Fe3O4@MN patch could rapidly increase by 40 â„ƒ in 1 min under NIR irradiation. In vitro experiment, the release rate of model drug in Fe3O4@MN reached âˆ¼ 80 % in 20 min and the doxycycline hydrochloride release rate of Fe3O4@MN reached âˆ¼ 70 % after 20 min of NIR irradiation, indicating the potential application of the synthesized microneedle patch for transdermal drug delivery. Further penetration test showed that the penetration depth of model drugs carried by Fe3O4@MN patch on the porcine skin under NIR irradiation was 150 - 200 µm longer than that of the patch without Fe3O4 nanoparticles.

Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.

Mutations of H-Ras, a member of the RAS family, are preferentially found in cutaneous squamous cell carcinomas (SCCs). H-Ras has been reported to induce autophagy, which plays an essential role in tissue homeostasis in multiple types of cancer cells and in fibroblasts, however, the potential role of H-Ras in regulating autophagy in human keratinocytes has not been reported. In this study, we found that the stable expression of the G12V mutant of H-RAS (H-Ras G12V ) induced autophagy in human keratinocytes, and interestingly, the induction of autophagy was strongly blocked by inhibiting the calcineurin/nuclear factor of activated T cells (NFAT) pathway with either a calcineurin inhibitor (Cyclosporin A) or a NFAT inhibitor (VIVIT), or by the small interfering RNA (siRNA) mediated knockdown of calcineurin B1 or NFATc1 in vitro, as well as in vivo. To characterize the role of the calcineurin/NFAT pathway in H-Ras induced autophagy, we found that H-Ras G12V promoted the nuclear translocation of NFATc1, an indication of the activation of the calcineurin/NFAT pathway, in human keratinocytes. However, activation of NFATc1 either by the forced expression of NFATc1 or by treatment with phenformin, an AMPK activator, did not increase the formation of autophagy in human keratinocytes. Further study revealed that inhibiting the calcineurin/NFAT pathway actually suppressed H-Ras expression in H-Ras G12V overexpressing cells. Finally, chromatin immunoprecipitation (ChIP) assays showed that NFATc1 potentially binds the promoter region of H-Ras and the binding efficiency was significantly enhanced by the overexpression of H-Ras G12V , which was abolished by treatment with the calcineurin/NFAT pathway inhibitors cyclosporine A (CsA) or VIVIT. Taking these data together, the present study demonstrates that the calcineurin/NFAT signaling pathway controls H-Ras expression and interacts with the H-Ras pathway, involving the regulation of H-Ras induced autophagy in human keratinocytes.

A carbazole compound, 9-ethyl-9H-carbazole-3-carbaldehyde, plays an antitumor function through reactivation of the p53 pathway in human melanoma cells.

p53, the major tumor suppressor, is frequently mutated in many cancers, and up to 84% of human melanomas harbor wild-type p53, which is considered to be an ideal target for melanoma therapy. Here, we evaluated the antitumor activity of a carbazole derivative, 9-ethyl-9H-carbazole-3-carbaldehyde (ECCA), on melanoma cells. ECCA had a selectively strong inhibitory activity against the growth of BRAF-mutated and BRAF-wild-type melanoma cells but had little effect on normal human primary melanocytes. ECCA inhibited melanoma cell growth by increasing cell apoptosis, which was associated with the upregulation of caspase activities and was significantly abrogated by the addition of a caspase inhibitor. In vivo assays confirmed that ECCA suppressed melanoma growth by enhancing cell apoptosis and reducing cell proliferation, and importantly ECCA did not have any evident toxic effects on normal tissues. RNA-Seq analysis identified several pathways related to cell apoptosis that were affected by ECCA, notably, activation of the p53 signaling pathway. Biochemical assays demonstrated that ECCA enhanced the phosphorylation of p53 at Ser15 in melanoma cells harboring wild-type p53, and importantly, the knockdown or deletion of p53 in those cells counteracted the ECCA-induced apoptosis, as well as senescence. Further investigations revealed that ECCA enhanced the phosphorylation of p38-MAPK and c-Jun N-terminal kinase (JNK), and treatment with either a p38-MAPK or a JNK inhibitor rescued the cell growth inhibition elicited by ECCA, which depended on the expression of the p53 gene. Finally, the combination of ECCA with a BRAF inhibitor significantly enhanced the growth inhibition of melanoma cells. In summary, our study demonstrates that the carbazole derivative, ECCA, induces melanoma cell apoptosis and senescence through the activation of p53 to significantly and selectively suppress the growth of melanoma cells without affecting normal human melanocytes, suggesting its potential to develop a new drug for melanoma therapy.

A superhydrophobic coating harvesting mechanical robustness, passive anti-icing and active de-icing performances.

HYPOTHESIS: Ice accretion is a challenging issue for various residential activities and industrial facilities. However, most of the current anti/de-icing coatings fail to maintain their properties when subject to frequent mechanical wear, and their limited functionality (either anti-icing or de-icing individually) cannot meet the requirement of all-weather utilization. EXPERIMENTS: Herein, a multifunctional superhydrophobic coating is prepared by compositing ferroferric oxide nanoparticles (Fe3O4 NPs) with fluorinated epoxy resin via an inverse infiltration process. The surface composition, morphology and wettability are systematically characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), laser scanning microscopy and contact angle tensiometer. The anti-icing and de-icing performances are evaluated by investigating the freezing delay and photothermal effect, respectively. FINDINGS: This coating shows outstanding water repellency (water contact angle up to 161.0°, sliding angle down to 1.4°) and can maintain superhydrophobicity within 400 cycles of tape peeling, 260 cycles of sandpaper abrasion or 25 cycles of sand impact. Besides, because the hydrophobic nano/micro hierarchical structures tremendously retard the heat transfer, the freezing process of water droplet on this coating can be apparently delayed by up to 35 min as compared to the uncoated substrate. Moreover, owing to the photothermal effect of the Fe3O4 NPs, the coating's surface temperature can be rapidly increased above 0 °C under infrared irradiation, which facilitates the ice melting on cold surfaces. Our work offers a versatile approach to address the icing problems in diverse weather conditions, which exhibits great prospects in various engineering applications.

An ultra-stretchable glycerol-ionic hybrid hydrogel with reversible gelid adhesion.

Functional hydrogels have attracted enormous interest as wet adhesives for biomedical research and engineering applications. However, reversible hydrogel adhesives that can be used for gelid conditions were rarely reported. In this work, we have developed a freezing-tolerant (freezing temperature < -50 °C), ultra-stretchable (stretch strain > 30000% at 25 °C) glycerol-ionic hydrogel via the ultraviolet curing of acrylamide monomer and hyper-branched polyethylenimine polymer in CaCl2-water-glycerol solution. The fabricated hydrogel exhibited reversible gelid adhesion, rapid self-healing (recover in 3 s) and weight-retaining (>2 weeks) properties. The hydrogel allows two iron substrates to adhere together at -40 °C with the lap-shear adhesion strength as high as ~1 MPa. Such strong adhesion measured was reversible, specifically achieving ~100% of initial adhesion strength at 25 °C and ~36% at -40 °C. Additionally, decreasing the testing temperature significantly improved the tensile strength but decreased the fracture strain of the hydrogel. Interestingly, lap-shear adhesion tests suggested that the gelid adhesion strength was enhanced by 130 times as the testing temperature decreased from 25 °C to -40 °C, which was mainly attributed to the enhanced mechanical strength of the bulk hydrogel as well as the increased surface interaction at gel-substrate interfaces. More importantly, the adhesion failure gradually changed from cohesive failure to adhesive failure as the temperature decreased. This work provides new practical and fundamental insights into developing multifunctional freezing-tolerant hydrogel adhesive for gelid conditions.

Probing the Self-Assembly and Nonlinear Friction Behavior of Confined Gold Nano-Particles.

For the wide application of nanoparticles (NPs) (e.g., in nanotribology), it is of fundamental and practical importance to understand the self-assembly and lubrication behavior of confined NPs. In this work, a systematic study was conducted to probe the assembly and associated surface forces of spherical gold nanoparticles (Au NPs, diameter ∼5 nm) confined between pairs of mica (negatively charged) and (3-aminopropyl)triethoxysilane modified mica (APTES-mica, positively charged) surfaces using a surface forces apparatus (SFA) under aqueous conditions. It is observed that Au NPs were squeezed out of the confined gap between two mica surfaces during the loading process, resulting from the repulsive electric-double layer force. In contrast, multilayers of Au NPs were confined between two APTES-mica surfaces because of the attractive double-layer force between oppositely charged Au NPs and APTES-mica. Interestingly, the interaction between Au NPs and APTES-mica is stronger than the interactions between Au NPs, resulting in the rearrangement of the confined Au NPs under shearing. Importantly, a large friction coefficient (µ > 0.7) with unexpected nonlinear stick-slip friction was observed when sliding two APTES-mica surfaces with thin layers of Au NPs (∼20 nm) confined in between. The observed stick-slip motion could be explained by the velocity-dependent friction model where a critical shear velocity was required for transiting from stick-slip to smooth sliding. Our study provides useful information on the assembly and interaction forces of confined nanoparticles on charged surfaces, with implications for predicting the behaviors of NPs under confinement in various engineering applications.