[Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats].

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

Inhibition of phosphoglycerate kinase 1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism.

AIMS: CD4+ T cells are the major drivers of cardiac-specific autoimmunity in myocarditis, specifically Th1, Treg, and most significant Th17 cells. But the molecular mechanisms of their activation remain unclear. We aimed to elucidate the regulatory role of phosphoglycerate kinase 1 (PGK1) in CD4+ T cells and experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: EAM was induced in BALB/c mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund's adjuvant. Single-cell sequencing analysis found that glycolysis and PGK1 expression were elevated in cardiac CD4+ T and Th17 cells from myocarditis mice. Mice treated with PGK1 inhibitor NG52 showed less cardiac inflammation and fibrosis and better contractile function, as well as reduced cardiac infiltrating Th17 and Th1 cells and increased proportion of Treg. NG52 suppressed CD4+ T cell activation and differentiation of mice and myocarditis patients in vitro. Mechanistically, inhibition of PGK1 suppressed glycolytic activity and decreased pyruvate dehydrogenase kinase 1 (PDHK1) phosphorylation, thereby increasing reactive oxygen species (ROS) production in mitochondria and thus preventing Th17 cell differentiation. CONCLUSION: PGK1 may act as a key metabolic regulator of CD4+ T cell differentiation and regulates Th17 cell differentiation by regulating glycolysis and the PDHK1-ROS axis. Targeting PGK1 might be a promising strategy for the treatment of myocarditis.

Transient receptor potential vanilloid 4 (TRPV4) in neutrophils enhances myocardial ischemia/reperfusion injury.

The Ca2+-permeable TRPV4 cation channel is expressed in neutrophils and contributes to myocardial ischemia/reperfusion injury. Here we tested the hypotheses that TRPV4 promotes neutrophil activation and subsequently aggregates myocardial ischemia/reperfusion injury. TRPV4 protein was confirmed in neutrophils, and its function was assessed by the current and intracellular Ca2+ concentration elevations evoked by TRPV4 agonists. Furthermore, TRPV4 agonists dose-dependently promoted migration toward fMLP, reactive oxygen species production, and myeloperoxidase release, which were prevented by pretreatment with a selective TRPV4 antagonist, in neutrophils from TRPV4 knockout mice, Ca2+-free medium, or BAPTA-AM + Ca2+-free medium. Blockade of TRPV4 also inhibited the effects of commonly used neutrophil activators fMLP and PMA. Mechanically, TRPV4 regulated neutrophil activation, particularly reactive oxygen species production, by affecting PKCα, P38, and AKT via Ca2+ signaling. In addition, isolated hearts infused with neutrophils from wild-type mice showed additional myocardial ischemia/reperfusion injuries but not those infused with TRPV4 knockout. Our study reveals that TRPV4-mediated neutrophil activation enhances myocardial ischemia/reperfusion injury, and it might be a novel therapeutic target for myocardial ischemia/reperfusion injury and other neutrophil-mediated inflammatory diseases.

A flexible tissue-carbon nanocoil-carbon nanotube-based humidity sensor with high performance and durability.

A flexible humidity sensor based on a tissue-carbon nanocoil (CNC)-carbon nanotube (CNT) composite has been investigated. Taking advantage of the excellent water absorption of tissue and the electrical sensitivity of CNCs/CNTs to humidity, this humidity sensor obtains outstanding humidity sensing performance, including a wide sensing range of 10-90% RH, a maximum response value of 492% (ΔR/R0) at 90% RH, a maximum sensitivity of 6.16%/% RH, a good long-time stability of more than 7 days, a high humidity resolution accuracy of less than 1% RH and a fast response time of 275 ms. Furthermore, the sensor also exhibits robust bending (with a curvature of 0.322 cm-1) and folding (up to 500 times) durability, and after being made into a complex "thousand paper crane" shape it still provides stable humidity sensing performance. As a proof of concept, this humidity sensor demonstrates excellent responsivity to human breath monitoring, non-contact fingertip humidity detection, water boiling detection and air humidity monitoring, indicating great potential in the fields of wearable devices, weather forecasting systems and other intelligent humidity monitoring devices.

Novel Wearable Pyrothermoelectric Hybrid Generator for Solar Energy Harvesting.

Recently, wearable energy harvesting systems have been attracting great attention. As thermal energy is abundant in nature, developing wearable energy harvesters based on thermal energy conversion processes has been of particular interest. By integration of a high-efficient solar absorber, a pyroelectric film, and thermoelectric yarns, herein, we design a novel wearable solar-energy-driven pyrothermoelectric hybrid generator (PTEG). In contrast to those wearable pyroelectric generators and thermoelectric generators reported in previous works, our PTEG can enable effective energy harvesting from both dynamic temperature fluctuations and static temperature gradients. Under an illumination intensity of 1500 W/m2 (1.5 sun), the PTEG successfully charges two commercial capacitors to a sum voltage of 3.7 V in only 800 s, and the total energy is able to light up 73 LED light bulbs. The volumetric energy density over the two capacitors is calculated to be 67.8 µJ/cm3. The practical energy harvesting performance of the PTEG is further evaluated in the outdoor environment. The PTEG reported in this work not only demonstrates a rational structural design of high-efficient wearable energy harvesters but also paves a new pathway to integrate multiple energy conversion technologies for solar energy collection.

Blockage of transient receptor potential vanilloid 4 prevents postoperative atrial fibrillation by inhibiting NLRP3-inflammasome in sterile pericarditis mice.

The incidence of atrial fibrillation (AF) increases after surgery and is associated with the activation of NLRP3-inflammation. Our previous studies have found that transient receptor potential vanilloid 4 (TRPV4) blockade reduces the susceptibility to AF, but its molecular mechanisms remains unclear. Therefore, we hypothesized that blockage of TRPV4 reduces the incidence of AF by inhibiting NLRP3-inflammasome in sterile pericarditis (SP) mice. In this study, we established SP mice by dusting talcum powder on atrial surfaces. We first confirmed that genetic or pharmacological TRPV4 inhibition reduced the susceptibility to AF in SP mice. We also found that the expression level of NLRP3-inflammasome and inflammatory cytokines significantly increased in the atria of SP mice, which further increased in application the TRPV4 agonist GSK1016790A (GSK101) and decreased in application the TRPV4 antagonist GSK2193874. More importantly, ERK inhibitor (U0126) or NF-κB inhibitor (Bay11-7082) could partially reverse GSK101-induced NLRP3-inflammasome up-regulation. Interestingly, U0126 can reversed GSK101-induced NF-κB phosphorylation, but Bay11-7082 cannot change GSK101-induced ERK phosphorylation. Finally, we shown that the activation of NLRP3-inflammasome and ERK/NF-κB signaling pathway significantly reduced in TRPV4-knockout SP mice. Collectively, our studies indicate that blockage of TRPV4 prevents AF in SP mice by inhibiting NLRP3-inflammasome through the ERK/NF-κB signaling pathway.

Highly Flexible, Stretchable, and Self-Powered Strain-Temperature Dual Sensor Based on Free-Standing PEDOT:PSS/Carbon Nanocoils-Poly(vinyl) Alcohol Films.

The wearable and self-powered sensors with multiple functions are urgently needed for energy saving devices, economical convenience, and artificial human skins. It is a meaningful idea to convert excess heat sources into power supplies for wearable sensors. In this report, we have fabricated a series of free-standing self-powered temperature-strain dual sensors based on poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS)/carbon nanocoils (CNCs)-poly(vinyl) alcohol composite films by a simple drop casting method. The Seebeck coefficients of the composite films were measured to be 19 µV/K. The sensor, with the addition of CNCs, showed a superior sensing performance to that without CNCs. PEDOT:PSS is used to provide a thermoelectric power to detect temperature changes and strain deformations. The minimum detect limit for the temperature difference was 0.3 K. Under a constant temperature gradient of 30 K, strains from 1 to 10% were detected without any external power supply. The films can be easily made into an array to detect the temperature of the fingers and motions of the wrist by attaching it to the human wrist directly. For the first time, due to the independent action of the thermoelectric material and strain sensing material, the thermoelectric voltage which is generated by a constant temperature difference is maintained under different strains. This kind of free-standing self-powered multifunctional sensors has great application prospects in the fields of healthcare and artificial intelligence in the future.

Identification of the distinctive role of DPT in dilated cardiomyopathy: a study based on bulk and single-cell transcriptomic analysis.

BACKGROUND: Dilated cardiomyopathy (DCM) is a common cause of heart failure. Cardiac remodeling is the main pathological change in DCM, yet the molecular mechanism is still unclear. Therefore, the present study aims to find potential crucial genes and regulators through bulk and single-cell transcriptomic analysis. METHODS: Three microarray datasets of DCM (GSE57338, GSE42955, GSE79962) were chosen from gene expression omnibus (GEO) to analyze the differentially expressed genes (DEGs). LASSO regression, SVM-RFE, and PPI network methods were then carried out to identify key genes. Another dataset (GSE116250) was used to validate these findings. To further identify DCM-associated specific cell types, transcription factors, and cell-cell interaction networks, GSEA, SCENIC, and CellPhoneDB were conducted on public datasets for single-cell RNA sequencing analysis of DCM (GSE109816 and GSE121893). Finally, reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemical were performed to validate DPT expression in fibroblasts and DCM. RESULTS: There were 281 DEGs between DCM and non-failing donors. CCL5 and DPT were identified to be key genes and both genes had a 0.844 area under the receiver operating curve (AUC) in the validation dataset. Further single-cell sequencing analysis revealed three main findings: (I) DPT was mainly expressed in fibroblasts and was significantly upregulated in DCM fibroblasts; (II) DPT+ fibroblasts were involved in the organization of the extracellular matrix (ECM) and collagen fibrils and were regulated by the transcription factor STAT3; and (III) DPT+ fibroblasts had high interactions with endothelial cells through including Ephrin-Eph, ACKR-CXCL, and JAG-NOTCH signal pathways. RT-PCR, western blot, and immunohistochemical confirmed that DPT was highly expressed and co-localized with Vimentin and p-STAT3 in DCM patients. STAT3 inhibitor S3I-201 reduced the expression of DPT in mouse cardiac fibroblasts. CONCLUSIONS: DPT could be used as a diagnostic marker and therapeutic target of DCM. DPT+ fibroblasts could be a novel regulator of the cardiac remodeling process in DCM.

Interleukin-6-Mediated-Ca2+ Handling Abnormalities Contributes to Atrial Fibrillation in Sterile Pericarditis Rats.

Pre-existing Ca2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with atrial fibrosis in several animal models of POAF, contributing to atrial arrhythmias. Here, we hypothesize that IL-6-mediated-Ca2+ handling abnormalities contribute to atrial fibrillation (AF) in sterile pericarditis (SP) rats, an animal model of POAF. SP was induced in rats by dusting atria with sterile talcum powder. Anti-rat-IL-6 antibody (16.7 µg/kg) was administered intraperitoneally at 30 min after the recovery of anesthesia. In vivo electrophysiology, ex vivo optical mapping, western blots, and immunohistochemistry were performed to elucidate mechanisms of AF susceptibility. IL-6 neutralization ameliorated atrial inflammation and fibrosis, as well as AF susceptibility in vivo and the frequency of atrial ectopy and AF with a reentrant pattern in SP rats ex vivo. IL-6 neutralization reversed the prolongation and regional heterogeneity of Ca2+ transient duration, relieved alternans, reduced the incidence of discordant alternans, and prevented the reduction and regional heterogeneity of the recovery ratio of Ca2+ transient. In agreement, western blots showed that IL-6 neutralization reversed the reduction in the expression of ryanodine receptor 2 (RyR2) and phosphorylated phospholamban. Acute IL-6 administration to isolated rat hearts recapitulated partial Ca2+ handling phenotype in SP rats. In addition, intraperitoneal IL-6 administration to rats increased AF susceptibility, independent of fibrosis. Our results reveal that IL-6-mediated-Ca2+ handling abnormalities in SP rats, especially RyR2-dysfunction, independent of IL-6-induced-fibrosis, early contribute to the development of POAF by increasing propensity for arrhythmogenic alternans.

Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts.

Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is involved in myocardial ischemia-reperfusion (IR) injury, yet its underlying molecular mechanism remains unclear. In this study, we isolated mice hearts for a Langendorff perfusion test and used HL-1 myocytes for in vitro assessments. We first confirmed that TRPV4 agonist (GSK101) enhanced myocardial IR injury, as demonstrated by the reduced recovery of cardiac function, larger myocardial infarct size, and more apoptotic cells. We also found that GSK101 could further increase the phosphorylation of JNK and CaMKII in isolated hearts during IR. Notably, GSK101 dose-dependently evoked the phosphorylation of JNK and CaMKII in isolated normal hearts. All above GSK101-induced effects could be significantly blocked by the pharmacological inhibition or genetic ablation of TRPV4. More importantly, JNK inhibition (with SP600125) or CaMKII inhibition (with KN93 or in transgenic AC3-I mice) could prevent GSK101-induced myocardial injury during IR. In HL-1 myocytes, GSK101 triggered Ca2+ influx and evoked the phosphorylation of JNK and CaMKII but these effects were abolished by removing extracellular Ca2+ or in the presence of a TRPV4 antagonist. Finally, we showed that in HL-1 myocytes and isolated hearts during IR, JNK inhibition significantly inhibited the phosphorylation of CaMKII induced by GSK101 but CaMKII inhibition had no effect on JNK activation induced by GSK101. Our data suggest that TRPV4 activation exacerbates myocardial IR injury via the JNK-CaMKII phosphorylation pathway.

Self-healing and anti-freezing graphene-hydrogel-graphene sandwich strain sensor with ultrahigh sensitivity.

Hydrogels with specially designed structures and adjustable properties have been considered as smart materials with multi-purpose application prospects, especially in the field of flexible sensors. However, most hydrogel-based sensors have low sensitivity, which inevitably affects their promotion in the market. Herein, a strain sensor comprising a poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) hybrid hydrogel sandwiched between two graphene layers was successfully constructed in a facile way, and it exhibited many excellent properties including extremely high sensitivity. The incorporation of glycerol ensured the good flexibility and anti-freezing performance of the hydrogel-based sensor even at -15 °C. The dynamic coordination bonds in the hydrogel-based sensor endowed it with excellent self-healing properties. In particular, the sandwich-structured hydrogel sensor showed a very high gauge factor (GF) value of 39 at the strain of 50%, which is much higher than those of most ordinary hydrogel-based strain sensors. A super stable signal value after 5000 strain cycles and a very short response time of 274 ms guaranteed the long-term usability and sensitivity of the hydrogel-based sandwich sensor. More importantly, the hydrogel-based sandwich sensor could detect both large and tiny human motions accurately and instantly in a series of real-time monitoring experiments, showing great potential for intelligent wearable electronic devices.

Facile Fabrication of High-Performance Pen Ink-Decorated Textile Strain Sensors for Human Motion Detection.

Recently, wearable strain sensors have increasingly attracted much attention due to their potential applications in human motion detection and personal health monitoring. To date, it is still a challenge to fabricate a flexible strain sensor with both comfort and high performance. In this study, we dip the commercially available spandex/polyamide fabric into carbonic pen ink to prepare a textile strain sensor with good skin affinity. The textile strain sensor exhibits a high gauge factor (∼62.9) and an excellent linearity (R2 ∼ 0.99) in the strain range of 0-30%. Both before and after washing, the sensor exhibits high stability in more than 5000 cycles. Owing to the facile integration of the ink-decorated fabric on clothes, the sensor can be conveniently attached to the human body to monitor human motions, thus showing great potential in practical applications.

Growth of Carbon Nanocoils by Porous α-Fe2O3/SnO2 Catalyst and Its Buckypaper for High Efficient Adsorption.

High-purity (99%) carbon nanocoils (CNCs) have been synthesized by using porous α-Fe2O3/SnO2 catalyst. The yield of CNCs reaches 9,098% after a 6 h growth. This value is much higher than the previously reported data, indicating that this method is promising to synthesize high-purity CNCs on a large scale. It is considered that an appropriate proportion of Fe and Sn, proper particle size distribution, and a loose-porous aggregate structure of the catalyst are the key points to the high-purity growth of CNCs. Benefiting from the high-purity preparation, a CNC Buckypaper was successfully prepared and the electrical, mechanical, and electrochemical properties were investigated comprehensively. Furthermore, as one of the practical applications, the CNC Buckypaper was successfully utilized as an efficient adsorbent for the removal of methylene blue dye from wastewater with an adsorption efficiency of 90.9%. This study provides a facile and economical route for preparing high-purity CNCs, which is suitable for large-quantity production. Furthermore, the fabrication of macroscopic CNC Buckypaper provides promising alternative of adsorbent or other practical applications.

A Facile Synthesis of Novel Amorphous TiO2 Nanorods Decorated rGO Hybrid Composites with Wide Band Microwave Absorption.

Amorphous structures may play important roles in achieving highly efficient microwave absorption performance due to the polarization losses induced by the disorders, vacancies and other functional groups existed in them. Herein, a kind of amorphous TiO2/rGO composite (a-TiO2/rGO) was successfully fabricated via a facile one-step solvothermal method. The complex permittivity of the composites can be regulated by adjusting the addition of precursor solution. The minimum reflection loss of a-TiO2/rGO composites reached -42.8 dB at 8.72 GHz with a thickness of 3.25 mm, and the widest efficient absorption bandwidth (EAB) was up to 6.2 GHz (11.8 to 18 GHz) with a thickness of only 2.15 mm, which achieved the full absorption in Ku band (12 to 18 GHz). Furthermore, the EAB was achieved ranging from 3.97 to 18 GHz by adjusting the thickness of the absorber, covering 87.7% of the whole radar frequency band. It is considered that the well-matched impedance, various polarization processes, capacitor-like structure and conductive networks all contributed to the excellent microwave absorption of a-TiO2/rGO. This study provides reference on constructing amorphous structures for future microwave absorber researches and the as-prepared a-TiO2/rGO composites also have great potential owing to its facile synthesis and highly efficient microwave absorption.

Sensitivity-Tunable Strain Sensors Based on Carbon Nanotube@Carbon Nanocoil Hybrid Networks.

A novel vanelike nanostructure based on the hybridization of carbon nanotubes and carbon nanocoils has been fabricated by a two-step chemical vapor deposition method. A flexible and sensitive strain sensor is prepared by coupling this hybrid structure with polydimethylsiloxane. By regulating the density and length of carbon nanotubes, the gauge factor and strain range of the sensors are tuned from 4.5 to 70 and 9 to 260%, respectively. These sensors exhibit high reliability and stability in a more than 10 000-cycle test and have a prompt response time of less than 37 ms. Owing to the tunable properties, these sensors show great potential in monitoring both subtle and large-scale displacements, which can meet the diverse demands of human motion monitoring.

A Novel Controllable Cell Array Printing Technique on Microfluidic Chips.

GOAL: The construction of single-cell array is known as the challenging technology to manipulate cell position and number and accomplish cell analysis in biomedical engineering. METHODS: We put forward a novel controllable cell printing technique for rapid, precise, convenient, high cell viability, multicellular, and high-throughput printing. We also proposed a novel microfluidic device to verify the effectiveness of the printing and study the migration ability and anti-cancer drug responses of cancer cell as important applications. RESULTS: This technique offered a minimum process time of 5 min, a maximum positional accuracy of 10 µm, 0.1 nL liquid volume level per droplet, above 87% cell viability after seven days and the ability to print different multicellular arrays. We found that the cell compared to cell culture in petri dish after 48 h. In addition, there was a significant different inhibition on cancer cells migration ability and cell drug activities with different concentrations of paclitaxel. CONCLUSION: This novel controllable cell array printing technique on the microfluidic platforms provides a useful method with high-quality printing and cell viability for the applications of single-cell analysis and high-throughput drug screening. SIGNIFICANCE: The controllable cell printing technique could apply in many biological processes and biomedical engineering applications, such as cell analysis, cancer development, and drug screening and metabolism. Combined with the microfluidic chips, tissue engineering, and sensors, this technique will be widely used for the construction and analysis of biological and biomedical model.

Construction of bionic tissue engineering cartilage scaffold based on three-dimensional printing and oriented frozen technology.

Articular cartilage (AC) has gradient features in both mechanics and histology as well as a poor regeneration ability. The repair of AC poses difficulties in both research and the clinic. In this paper, a gradient scaffold based on poly(lactic-co-glycolic acid) (PLGA)-extracellular matrix was proposed. Cartilage scaffolds with a three-layer gradient structure were fabricated by PLGA through three-dimensional printing, and the microstructure orientation and pore fabrication were made by decellularized extracellular matrix injection and directional freezing. The manufactured scaffold has a mechanical strength close to that of real cartilage. A quantitative optimization of the Young's modulus and shear modulus was achieved by material mechanics formulas, which achieved a more accurate mechanical bionic and a more stable interface performance because of the one-time molding process. At the same time, the scaffolds have a bionic and gradient microstructure orientation and pore size, and the stratification ratio can be quantitatively optimized by design of the freeze box and temperature simulation. In general, this paper provides a method to optimize AC scaffolds by both mechanics and histology as well as a bionic multimaterial scaffold. This paper is of significance for cell culture and clinical transplantation experiments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1664-1676, 2018.

An AC electrothermal self-circulating system with a minimalist process to construct a biomimetic liver lobule model for drug testing.

Liver-on-chip, due to its precision and low cost for constructing in vitro models, has tremendous potential for drug toxicity testing and pathological studies. By applying APAP (acetaminophen) treatment of different concentrations, a dynamic self-circulating liver lobule model for drug testing was proven useful for emulating the human physiological system. However, the demand for a dynamic system of on-chip organs is difficult to fulfil due to the relatively cumbersome fabrication processes. In this paper, the design and fabrication of an AC electrothermal self-circulating system combined with a 3D biomimetic liver lobule is described. The system was fabricated using a low-cost ITO laser etching process within a few seconds. A large number of interdigital electrodes were arranged in a limited space to increase the fluid flow-driven efficiency. The liver lobule consists of two parts, a hepatocyte cell-laden layer and an endothelial layer, which exhibit a sandwich radial shaped pattern that is more bionic in structure and function. By evaluating the velocity and temperature in the self-circulating system at various voltages and frequencies, we obtained a set of reliable input parameters to provide an adequate supply of culture fluid without cell damage. The metabolism of the liver lobule in dynamic culture and static culture was compared based on cell viability, albumin secretion and urea synthesis.

A novel tissue-engineered 3D tumor model for anti-cancer drug discovery.

Cancer biology and drug discovery are heavily dependent on conventional 2D cell culture systems. However, a 2D culture is significantly limited by its ability to reflect 'true biology' of tumor in vivo. Three-dimensional (3D) in vitro cell culture models have been introduced to aid cancer drug discovery by better modeling the tumor microenvironment. Here, decellularized lung scaffolds cultured with MCF-7 cancer cells were bioengineered as a platform to study tumor development and anti-cancer drug evaluation. Excellent cell compatibility of decellularized lung scaffolds promoted cell growth and proliferation. Multicellular tumor cell spheroids (tumoriods) were formed and enlarged exclusively in decellularized lung scaffolds over time. The expression of breast cancer biomarkers (BRCA1 and HER2) in MCF-7 cells significantly increased in the lung matrix compared to those cultured in 2D systems. Insufficient oxygen and nutrient diffusion into the internal surface of lung scaffolds resulted in intracellular hypoxia, quantified by a significant upregulation of HIF-1α protein expression compared to that of cell monolayers. Higher survival rates after exposure to 5-FU were observed in lung scaffolds (52.04%) compared to that in 2D systems (18.39%) on day 3 of culture. Overall, this new breast tumor system provides a promising platform to study breast cancer progression and develop new targeted therapeutic strategies.