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In clinical settings the wound-dressing was required easy to use and can match the wound area immediately, at the same time they need to have the properties of hemostats, anti-inflammation and promoting wound healing. To get an ideal wound dressing, we developed a type of gel-like wound adhesive patch from spraying double-network hydrogel, which own the properties of self-antibacterial and can promote wound healing. By spraying, the gel-like wound adhesive patch can match the wound area immediately and form a gel-film in 10 s. Sodium carboxymethyl cellulose as pH sensitive materials accelerated the speed to form the gel-film and enhanced ductility of the wound adhesive patch. In vitro experiments show that, this gel-like wound adhesive patch can promote cell proliferation and reduce cell apoptosis. In vivo studies show that, compared with commercialized wound dressings in clinic using, the spraying gel-like wound adhesive patch from our work has a better effect on wound healing. In conclusion, the spraying gel-like wound patch in our work is easy to use and can form a gel-film match on wound area in a short time, also it has the properties of hemostats, anti-inflammation and promoting wound healing. Its feasibility for mass production shows a good potential for commercial use.

Bioelectricity plays a significant role in major biological processes and electrical stimulation is an effective and non-invasive way to promote cellular growth, differentiation and tissue regeneration. In tissue engineering, piezoelectric materials not only act as modulators to regulate behaviors and functions of cells and tissues, but are also used as scaffolds to regulate and guide cell growth and matrix synthesis, thus promoting the formation of new tissue. Piezoelectronic electrons are produced from piezoelectric materials upon mechanical stimuli and have similar effects on cells as an external electrical field. Devices based on piezoelectronics have been widely applied in bioelectronics and biomedical fields. In this review, the effects of piezoelectronic electrons on cells and their possible mechanisms are briefly introduced. Then, we overview the applications of piezoelectronic electrons in cell regulation and tissue regeneration according to the type of cells and tissues. Finally, future perspectives and challenges are also provided.

The utilization of thermal energy from different sources is an important development direction for conserving energy. With the development of technology, refined and rapid utilization of thermal energy is required. Traditional thermal conductive materials cannot meet the growing needs of human beings. Therefore, people pay attention to two-dimensional graphene film materials for their thermal conductivity. This review collects current modeling group of thermal transport on graphene, including non-equilibrium Green function (NEGF) theory, molecular dynamics (MD) simulations modeling and Boltzmann transport equation method. These models can well explain several phenomena of phonon transport in graphene. Further, structural defects were discussed and expounded the effect for graphene thermal conductivity, including doping, grain boundary and defects. Deeply understanding of defects on graphene, we can better grasp the thermal conductivity of graphene from the microscopic point of view.

AIM To explore the role of DNA methylation in the innate immunity of the dental pulp, this study investigated the effect of 5-aza-2'-deoxycytidine (AZA) on lipoteichoic acid (LTA)-induced cytokine production and related intracellular signalling pathways in human odontoblast-like cells (hOBs). METHODOLOGY hOBs were cultured and differentiated from human dental pulp tissue, and the odontoblastic phenotype of the cells was detected using immunofluorescence, qRT-PCR and Western blotting. hOBs were pretreated with AZA and then stimulated with 10 μg mL-1 LTA. The levels of 42 cytokines related to immunity and inflammation were examined using a cytokine antibody array and verified using qRT-PCR and ELISA. The effect of AZA on the LTA-induced NF-κB and MAPK signalling pathways was explored using Western blotting. The cells were treated with the specific NF-κB inhibitor PDTC and MAPK inhibitors (the ERK inhibitor U0126, the p38 inhibitor SB203580, and the JNK inhibitor SP600125) to further confirm the role of the signalling pathways in LTA-treated hOBs. DNA immunoprecipitation-PCR was used to examine the dynamic methylation status of the gene promoters of myeloid differentiation primary response 88 (MyD88) and tumour necrosis factor receptor-associated factor 6 (TRAF6) in the LTA-induced hOBs. Statistical analyses of the differences between two groups were performed using Student's t-test. One-way analysis of variance (anova) or repeated-measures anova with a post hoc Dunnett's test was used to assess the differences between multiple sets of data. P

Dual network (DN) hydrogels with excellent mechanical strength and controllable component adjustment characteristics have a broad application range in the field of biomedicine. However, the tissue adhesion, skin affinity, self-healing, and antibacterial properties of DN hydrogels are inadequate for their application as skin patches. In this work, we prepared dopamine/zinc oxide (DOPA/ZnO) doped poly(N-hydroxyethyl acrylamide) (p(HEAA))/agar DN hydrogels and combined them to obtain a bilayer hydrogel (two-layer gel) with moisturizing properties. Upon incorporating 0.86 wt% of dopamine (DOPA), the resultant DOPA/p(HEAA))/agar DN hydrogel (DOPA@DNG) exhibited high tensile strain (up to 1600%), excellent self-repair ability, and tissue adhesion. ZnO/p(HEAA))/agar DN hydrogel (ZnO NG) obtained by incorporating 2 w/v ZnO nanoparticles (ZnO NPs) achieved high tensile strength (1.2 MPa), good antibacterial ability, and low charge transfer resistance. Moreover, ZnO NG, which has a tight structure, was employed as a protective layer for the two-layer gel, which can effectively slow down the excessive evaporation of water to protect the DOPA@DNG stability as a skin patch. Evidence showed that the two-layer hydrogel has water retention. Water retention still remains at over 50% after keeping the hydrogel in air for 3 days. These properties mean the two-layer gel based on the DOPA/ZnO doped DN hydrogels could be used as a transdermal patch for numerous applications in drug delivery, wearable devices, and electronic skin.

Description, Wireless and passive bioelectronic medicines mimic the biological cues of the extracellular matrix., The biophysical characteristics of the extracellular matrix (ECM), such as a three-dimensional (3D) network and bioelectricity, have a profound influence on cell development, migration, function expression, etc. Here, inspired by these biophysical cues of ECM, we develop an electromechanical coupling bio-nanogenerator (bio-NG) composed of highly discrete piezoelectric fibers. It can generate surface piezopotential up to millivolts by cell inherent force and thus provide in situ electrical stimulation for the living cells. Besides, the unique 3D space in the bio-NGs provides an ECM-like growth microenvironment for cells. As a result, our bio-NGs effectively promote cell viability and development and, more importantly, maintain its specific functional expression. These advanced in vitro bio-NGs are expected to fill the gap between the inaccurate 2D systems and the expensive and time-consuming animal models, mimicking the complexity of the ECM and the physiological relevance of an in vivo biological system.

Zwitterionic materials are an important class of antifouling biomaterials for various applications. Despite such desirable antifouling properties, molecular-level understanding of the structure–property relationship associated with surface chemistry/topology/hydration and antifouling performance still remains to be elucidated. In this work, we computationally studied the packing structure, surface hydration, and antifouling property of three zwitterionic polymer brushes of poly(carboxybetaine methacrylate) (pCBMA), poly(sulfobetaine methacrylate) (pSBMA), and poly((2-(methacryloyloxy)ethyl)phosporylcoline) (pMPC) brushes and a hydrophilic PEG brush using a combination of molecular mechanics (MM), Monte Carlo (MC), molecular dynamics (MD), and steered MD (SMD) simulations. We for the first time determined the optimal packing structures of all polymer brushes from a wide variety of unit cells and chain orientations in a complex energy landscape. Under the optimal packing structures, MD simulations were further conducted to study the structure, dynamics, and orientation of water molecules and protein adsorption on the four polymer brushes, while SMD simulations to study the surface resistance of the polymer brushes to a protein. The collective results consistently revealed that the three zwitterionic brushes exhibited stronger interactions with water molecules and higher surface resistance to a protein than the PEG brush. It was concluded that both the carbon space length between zwitterionic groups and the nature of the anionic groups have a distinct effect on the antifouling performance, leading to the following antifouling ranking of pCBMA > pMPC > pSBMA. This work hopefully provides some structural insights into the design of new antifouling materials beyond traditional PEG-based antifouling materials.

Tough and adhesive hydrogels have shown great potential in wearable devices, flexible electronics, and human–machine interfaces. However, most existing tough hydrogels have weak surface adhesion, o...

The prevalence of functionalized nanoparticles in biological and clinical fields attracts intensive toxicology investigations. Minimizing the nanoparticles’ biohazard remains a challenge due to the insufficient understanding on the nanoparticle-induced cell death mechanism. In the presented study, we observed the lysosome and genome injuries and so caused cell cycle changes and regulations of retinal ganglion neuron cell 5 (RGC-5) induced by aminated and alkylated nanoparticles. Alkylated nanoparticles induced malignant lysosome and genome damages followed by severe post-self-repair responses. RGC-5 treated with alkylated nanoparticles presented dramatic S phase prolongation resulted from cyclin E accumulation mediated by Fbw7 downregulation, which assisted DNA replication after failed self-repair of the malignantly damaged DNA caused by alkylated nanoparticles. Differently, aminated nanoparticles in RGC-5 induced moderate lysosome and genome injuries and these damages could be repaired in the p21-involved pathway, so that cells did not induce apparent cyclin E accumulation nor Fbw7 downregulation as post-self-repair response. These results helped us to understand the toxicity of analogous nanoparticles on retinal ganglions such as glaucoma treatment. This work provides new insights into nanoparticle functionalization and toxicity in relation to the research on the toxicology and pathology of nerve cells.

Limited understanding of mitochondria disorders that induced by nanoparticles is a stumbling block for anti-cancer drug delivery targeting strategy. In present study, C6 glioma cells were exposed to aminated and alkylated SiO2 nanoparticles for mitochondrion disordering and cell metabolism study. Collective results showed that aminated nanoparticles tend to trigger the cell-repair mechanism in cancer cells while alkylated nanoparticles could cause irreversible damages on cancer cells, although both types of the particles were proved to damage mitochondrion. The underlying mechanism show that aminated nanoparticles induced proton-stuck effect in mitochondrion and self-repairing in cancer cells by up-regulating p21. Otherwise, alkylated nanoparticles damaged mitochondrion and induced phosphorylated cyclin E accumulation lead to Fbw7 down-regulation caused further S phase arrest and severe late apoptosis. This work can help us elucidate the mechanism of the clinic application of nano-drug carriers.

Implantable pressure biosensors show great potential for assessment and diagnostics of pressure-related diseases. Here, we present a structural design strategy to fabricate core/shell polyvinylidene difluoride (PVDF)/hydroxylamine hydrochloride (HHE) organic piezoelectric nanofibers (OPNs) with well-controlled and self-orientated nanocrystals in the spatial uniaxial orientation (SUO) of β-phase-rich fibers, which significantly enhance piezoelectric performance, fatigue resistance, stability, and biocompatibility. Then PVDF/HHE OPNs soft sensors are developed and used to monitor subtle pressure changes in vivo. Upon implanting into pig, PVDF/HHE OPNs sensors demonstrate their ultrahigh detecting sensitivity and accuracy to capture micropressure changes at the outside of cardiovascular walls, and output piezoelectric signals can real-time and synchronously reflect and distinguish changes of cardiovascular elasticity and occurrence of atrioventricular heart-block and formation of thrombus. Such biological information can provide a diagnostic basis for early assessment and diagnosis of thrombosis and atherosclerosis, especially for postoperative recrudescence of thrombus deep within the human body.

Breast cancer is one of the most common cancers in the world, survival rates of breast cancer are rising as screening and treatment improve. Many new technologies applied in the biomedical domain have been born for rapid diagnosis and treatment. In this work, visualization cell microarray chip with three-dimensional (3D) embedded cell scaffold for cell diagnosis and treatment was designed. DNA segment, targeting on breast cancer cells SK-BR-3, were modified with camptothecin and used as model drug. Cell microarray chip system successfully control the diffusion of small molecules and locally introduced the compounds into cells. 3D embedded cell scaffold in the cell array chip afforded an environment with continuous medium supplementary and help controlling the diffusion of small molecules drugs. By cell microarray chip system, SK-BR-3 was targeted screening and killing in one step. Cell microarray chip system can achieve accurate, rapid diagnosis and target treatment of breast cancer cells SK-BR-3 and have a potential to develop to be an effective and accurate drug screen method for evaluating the drug effect of the booming chemicals.

Dual network (DN) hydrogels with excellent mechanical strength and controllable component adjustment characteristics have a broad application range in the field of biomedicine. However, the tissue adhesion, skin affinity, self-healing, and antibacterial properties of DN hydrogels are inadequate for their application as skin patches. In this work, we prepared dopamine/zinc oxide (DOPA/ZnO) doped poly(N-hydroxyethyl acrylamide) (p(HEAA))/agar DN hydrogels and combined them to obtain a bilayer hydrogel (two-layer gel) with moisturizing properties. Upon incorporating 0.86 wt% of dopamine (DOPA), the resultant DOPA/p(HEAA))/agar DN hydrogel (DOPA@DNG) exhibited high tensile strain (up to 1600%), excellent self-repair ability, and tissue adhesion. ZnO/p(HEAA))/agar DN hydrogel (ZnO NG) obtained by incorporating 2 w/v ZnO nanoparticles (ZnO NPs) achieved high tensile strength (1.2 MPa), good antibacterial ability, and low charge transfer resistance. Moreover, ZnO NG, which has a tight structure, was employed as a protective layer for the two-layer gel, which can effectively slow down the excessive evaporation of water to protect the DOPA@DNG stability as a skin patch. Evidence showed that the two-layer hydrogel has water retention. Water retention still remains at over 50% after keeping the hydrogel in air for 3 days. These properties mean the two-layer gel based on the DOPA/ZnO doped DN hydrogels could be used as a transdermal patch for numerous applications in drug delivery, wearable devices, and electronic skin.

Despite the boom in the water-triggered electric power generation technologies, few attempts have been made with a broader horizonyielding the electricity from sweat, which is of great value for low-power-consumption wearable electronics. Here, an electromechanical coupling and humidity-actuated two-in-one humidity actuator-driven piezoelectric generator (HAPG) are reported, that can yield continuous electric power from fluctuations in the ambient humidity. It is composed of polyvinyl alcohol (PVA)-wrapped highly aligned dopamine (DA)/polyvinylidene fluoride (PVDF) shell/core nanofibers (PVA@DA/PVDF NFs). As-received PVA@DA/PVDF NFs can exchange water with the ambient humidity to perform expansion and contraction and convert them into electric power. An all-fiber-based portable HAPG is fabricated and tested on human palm skin. The devices show high sensitivity and accuracy for converting the mental sweating-derived continuous moisture fluctuations into electric power. This electric power can be stored in capacitors, which is expected to power micro- and nano-electronic devices or be used in electrotherapy such as electrical stimulation to promote wound healing. Beyond this, the obtained voltage profiles exhibit unique features that can reflect the typical sweat damping oscillation curve features.

Organic pollution is considered as a long-term, urgent global issue for energy, environmental, and ecological applications. Carbon-based materials have shown great potential in addressing this global issue. However, development of low-cost and high-performance of carbon-based three-dimensional materials has also proven to challenging for removal of organic pollutants from water. Here, we developed a new technique combining a liquid-assisted electrospinning and interface self-assembly of graphene to successfully fabricate novel graphene fluffy nanofibrous scaffold (GFNs) as an efficient organic pollution absorbent. The resultant GFNs with several advantages of distinctive 3D fluffy macro-structure, super porosity, low density, strong mechanical stability, and super hydrophobicity/oleophicity, demonstrated high adsorption capacity for organic solvents (201 times their own weight) and oils (119 times their own weight), as well as excellent recyclability by simple extrusion. Different from conventional graphe...

Misfolded protein aggregates formed by the same (homologous) or different (heterologous/cross) sequences are the pathological hallmarks of many protein misfolding diseases (PMDs) including Alzheimer's disease (AD) and type 2 diabetes (T2D). Different from homologous-amyloid aggregation that is solely associated with a specific PMD, cross-amyloid aggregation (i.e. cross-seeding) of different amyloid proteins is more fundamentally and biologically important for understanding and untangling not only the pathological process of each PMD, but also a potential molecular cross-talk between different PMDs. However, the cross-amyloid aggregation is still a subject poorly explored and little is known about its sequence/structure-dependent aggregation mechanisms, as compared to the widely studied homo-amyloid aggregation. Here, we review the most recent and important findings of amyloid cross-seeding behaviors from in vitro, in vivo, and in silico studies. Some typical cross-seeding phenomena between Aβ/hIAPP, Aβ/tau, Aβ/α-synuclein, and tau/α-synuclein are selected and presented, and the underlying specific or general cross-seeding mechanisms are also discussed to better reveal their sequence-structure-property relationships. The potential use of the cross-seeding concept to design amyloid inhibitors is also proposed. Finally, we offer some personal perspectives on current major challenges and future research directions in this less-studied yet important field, and hopefully this work will stimulate more research to explore all possible fundamental and practical aspects of amyloid cross-seeding.

Due to inhomogeneous molecular structure and inherent flexibility of organic piezoelectric materials, the improvement in piezoelectric performances is extremely challenging. Herein, a novel sheath-gas-assisted electrospinning method was designed to induce rapid recrystallization and a stretching effect on the PVDF molecular chains, which led to significant promotion in the formation of β and γ crystal phases in PVDF nanofibers and the highest piezoelectric properties reported to date for pure organic piezoelectric materials. By using the PVDF nanofibers for energy harvesting in vivo and in vitro, the motion sensor and implantable nanogenerators displayed excellent sensitivity under an extremely low working frequency of ∼0.1 Hz and considerable output voltage of 0.4-0.6 V cm-2 driven by the femoral artery and carotid artery for the first time. Furthermore, we demonstrated that the nanofibers have outstanding biocompatibility and can provide a spontaneous microelectronic stimulation effect to improve the growth of nerve cells. Thus, we envision that the high-performance piezoelectric nanofibers may serve as a powerful tool for developing future flexible force-sensitive microelectric devices and generators for applications in bioelectronics and biomedicine.

The rapid development of a self-powered system (SPS) has aroused an increasing interest in the field of wearable electronics. The current development trend in wearable electronics is toward integration, portability, miniaturization, and sustainability. Hence, a wearable piezoelectric-driven self-powered patterned electrochromic supercapacitor (ESC) is presented here, which is integrated with the energy harvesting, conversion, storage and indication technologies. The patterned polyaniline (PANI) electrodes electrodeposited by coupling cyclic voltammetric and galvanostatic (CV-GS) techniques were assembled as patterned ESC, which served to store the energy and indicate the charging/discharging status simultaneously. With the advantages of flexibility and biocompatibility, the polyvinylidene difluoride (PVDF) nanofibers were fabricated by electrospinning to establish the piezoelectric nanogenerators (PENGs) as the energy-harvesting device, which can be attached to human body to harvest mechanical kinetic ene...

Adipose derived stem cells (ADSCs) have been proved as an abundant and accessible cell source with the ability to differentiate into neuron-like cells. However, the low differentiation efficiency puts forward an important challenge to practical applications in clinic. Considering of the good biocompatibility of graphene-based materials and the potential interaction between graphene and cells mentioned in previous studies, herein, we investigated the effect of graphene oxide (GO) and reduced graphene oxide (rGO) mats on neurogenic differentiation of the ADSCs. We demonstrated the excellent capabilities of graphene-based mats, especially GO to support the neural differentiation of ADSCs. By comparing the observation under an optical microscope and fluorescence microscope, the conversion rate of neuron-like cells reached about 90%. We consider that GO mat is better for promoting the differentiation of ADSCs into neuron-like cells, which compared to rGO based platforms. Meanwhile, we made an analysis of the mechanism by which graphene induced the differentiation of ADSCs to neuron-like cells. The data obtained here highlight the effect of GO mat on neurogenic differentiation of ADSCs and implicate the potential of graphene-based materials in application of neural tissue engineering for the limited self-repair capability of nerve cells.

Understanding the internal cellular processes of micron/nanoparticles will be important for particles toxicity studies or drug-delivery systems designing. The details and mechanisms of the cellular up-take process of micron/nano particles can hardly be described in real-time. In this study, cellular internalization of micron/nanoparticles was investigated by fluorescence spectroscopy, flow cytometry and sum frequency generation vibrational spectroscopy (SFG). Model cell membranes such as substrate supported lipid bilayers and lipid vesicles were used in this research. Especially, SFG was used to examine the behavior of each leaflet of the lipid bilayer while interacting with micron/nanoparticles. Experiments of SFG show direct evidences that micron/nanoparticles attachment lead to the lipid orientation. Vesicle dye-leakage model were used to study long-term interactions on model membrane. Results from this study provide in-depth insight into the molecular interactions between micron/nanoparticles and cell membranes, which will help to understand the particles toxicity and will be useful for the designing of micron/nanoparticles for applications.