Despite advances in the bioprinting technology, biofabrication of circumferentially multilayered tubular tissues or organs with cellular heterogeneity, such as blood vessels, trachea, intestine, ...colon, ureter, and urethra, remains a challenge. Herein, a promising multichannel coaxial extrusion system (MCCES) for microfluidic bioprinting of circumferentially multilayered tubular tissues in a single step, using customized bioinks constituting gelatin methacryloyl, alginate, and eight‐arm poly(ethylene glycol) acrylate with a tripentaerythritol core, is presented. These perfusable cannular constructs can be continuously tuned up from monolayer to triple layers at regular intervals across the length of a bioprinted tube. Using customized bioink and MCCES, bioprinting of several tubular tissue constructs using relevant cell types with adequate biofunctionality including cell viability, proliferation, and differentiation is demonstrated. Specifically, cannular urothelial tissue constructs are bioprinted, using human urothelial cells and human bladder smooth muscle cells, as well as vascular tissue constructs, using human umbilical vein endothelial cells and human smooth muscle cells. These bioprinted cannular tissues can be actively perfused with fluids and nutrients to promote growth and proliferation of the embedded cell types. The fabrication of such tunable and perfusable circumferentially multilayered tissues represents a fundamental step toward creating human cannular tissues.
A multichannel coaxial extrusion system for microfluidic bioprinting of circumferentially multilayered tubular tissues is presented. The fabrication of such tunable and perfusable circumferentially multilayered tissues represents a fundamental step toward creating human cannular tissues.
Shape memory polymers (SMPs) will come to act an indispensable part in numerous aspects of human activity. However, the low mechanical strengths and thermal conductivities of SMPs have largely ...restricted their applications. Remarkable improvements in the mechanical properties and thermal conductivities of SMPs via introducing thermal conductivity fillers have been achieved, though the fillers acted as obstructors or promoters for the thermal response speed of SMPs were unclear. In the present study, ternary hybrid polymeric shape memory composites of graphene oxide/carbon nanotube/waterborne epoxy (GO/CNT/WEP) were fabricated, where GO acted as a non-covalent dispersant for CNT in WEP and as a reactive secondary reinforcing agent to improve the mechanical strength and thermal conductivity of WEP. The experimental results showed that GO and CNT were uniformly dispersed and well incorporated into WEP matrix, significantly enhanced the mechanical properties, thermal conductivity and thermal response speed of the GO/CNT/WEP composites. Moreover, the thermal response speed of the shape memory composites was controlled by their thermal conductivity at low filler content, while the storage modulus was the dominant factor for the thermal response speeds of the shape memory composites at filler content higher than 2 wt%.
Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR ...mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.
Bioprinting is the most convenient microfabrication method to create biomimetic three‐dimensional (3D) cardiac tissue constructs, that can be used to regenerate damaged tissue and provide platforms ...for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, a gold nanorod (GNR)‐incorporated gelatin methacryloyl (GelMA)‐based bioink is developed for printing 3D functional cardiac tissue constructs. The GNR concentration is adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentrations of GNR, the nanocomposite bioink has a low viscosity, similar to pristine inks, which allows for the easy integration of cells at high densities. As a result, rapid deposition of cell‐laden fibers at a high resolution is possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells show improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridge the electrically resistant pore walls of polymers, improve the cell‐to‐cell coupling, and promote synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.
A gold nanorod‐incorporated gelatin methacryloyl‐based bioink for printing of 3D cardiac tissue constructs is developed. The rapid deposition of the cell‐laden fibers at a high resolution is achieved, while reducing the shear stress on the encapsulated cells. The incorporated gold nanorods improve the electrical propagation between cardiac cells and promote their functional improvement in the printed cardiac construct.
•MALAT1 expression was highly expressed in AML patients.•miR-96 expression was lowly expressed in AML patients.•Knockdown of MALAT1 inhibited proliferation and induced apoptosis of AML ...cells.•Knockdown of MALAT1 enhanced Ara-C sensitivity in AML cells.•miR-96 was a target of MALAT1 in AML cells.
Drug resistance remains a major cause of relapse and therapeutic failure in acute myeloid leukemia (AML). Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been documented to act as an oncogene and is frequently highly expressed in human cancers including AML. However, the function and molecular mechanism of MALAT1 in regulating cytarabine (Ara-C) resistance of AML are largely unknown. The expressions of MALAT1 and miR-96 in AML patients and healthy controls were examined by qRT-PCR. CCK-8 and flow cytometry assay were performed to assess the proliferation and apoptosis of AML cells. The interaction between MALAT1 and miR-96 was investigated by luciferase reporter assay. We found that MALAT1 was upregulated while miR-96 was downregulated in AML patients compared with healthy controls. A negative correlation between MALAT1 and miR-96 expressions was observed in AML patients. Knockdown of MALAT1 inhibited the proliferation, induced apoptosis, and enhanced Ara-C sensitivity of AML cells. Additionally, MALAT1 suppressed miR-96 expression by acting as a molecular sponge of miR-96 in AML cells. miR-96 downregulation abolished the effects of MALAT1 knockdown on the proliferation, apoptosis, Ara-C sensitivity in AML cells. In conclusion, MALAT1 knockdown inhibited proliferation, promoted apoptosis and enhanced Ara-C sensitivity in AML cells by upregulating miR-96, providing novel insights into the critical role of MALAT1 as a miRNA sponge in AML.
Engineered nano–bio cellular interfaces driven by 1D vertical nanostructures (1D‐VNS) are set to prompt radical progress in modulating cellular processes at the nanoscale. Here, tuneable cell–VNS ...interfacial interactions are probed and assessed, highlighting the use of 1D‐VNS in immunomodulation, and intracellular delivery into immune cells—both crucial in fundamental and translational biomedical research. With programmable topography and adaptable surface functionalization, 1D‐VNS provide unique biophysical and biochemical cues to orchestrate innate and adaptive immunity, both ex vivo and in vivo. The intimate nanoscale cell–VNS interface leads to membrane penetration and cellular deformation, facilitating efficient intracellular delivery of diverse bioactive cargoes into hard‐to‐transfect immune cells. The unsettled interfacial mechanisms reported to be involved in VNS‐mediated intracellular delivery are discussed. By identifying up‐to‐date progress and fundamental challenges of current 1D‐VNS technology in immune‐cell manipulation, it is hoped that this report gives timely insights for further advances in developing 1D‐VNS as a safe, universal, and highly scalable platform for cell engineering and enrichment in advanced cancer immunotherapy such as chimeric antigen receptor‐T therapy.
1D vertical nanostructures (1D‐VNS) are used in immunomodulation and intracellular delivery into immune cells. 1D‐VNS produce biophysical and biochemical signals to modulate cellular deformation, membrane tension, and immune activation cascades; they facilitate efficient intracellular delivery of diverse therapeutic cargoes into immune cells.
Objectives
Docking Protein 3 (DOK3) is an adapter protein that has been implicated in various cellular processes relevant to diseases, such as cancer. In this study, we aimed to evaluate the role of ...DOK3 in kidney renal clear cell carcinoma (KIRC) by examining how its expression levels are correlated with patient characteristics and prognosis.
Methods
We analyzed KIRC-related data from The Cancer Genome Atlas and used several bioinformatics tools, such as LinkedOmics and Oncomine, to evaluate DOK3 mRNA expression in KIRC. DOK3 protein expression was examined in 150 clinical KIRC samples and 100 non-cancerous renal tissues with immunohistochemistry assays. The prognostic value of DOK3 mRNA expression on patient overall survival was analyzed retrospectively using Kaplan–Meier survival and Cox regression analyses.
Results
DOK3 mRNA expression was notably higher in KIRC samples compared with normal tissues. Significant correlations were found between DOK3 mRNA expression levels and tumor size, lymph node metastasis, distant metastasis, and pathological grade using the bioinformatics data. This was confirmed at the protein level with immunohistochemistry data. Survival analyses indicated that elevated DOK3 expression is linked to a lower overall survival rate in KIRC patients.
Conclusions
DOK3 is a potential biomarker for determining KIRC patient clinical prognosis.
In this work, a wire-shaped flexible strain sensor was fabricated by encapsulating conductive carbon thread (CT) with polydimethylsiloxane (PDMS) elastomer. The key strain sensitive material, CT, was ...prepared by pyrolysing cotton thread in N
atmosphere. The CT/PDMS composite wire shows a typical piezo-resistive behavior with high strain sensitivity. The gauge factors (GF) calculated at low strain of 0-4% and high strain of 8-10% are 8.7 and 18.5, respectively, which are much higher than that of the traditional metallic strain sensor (GF around 2). The wire-shaped CT/PDMS composite sensor shows excellent response to cyclic tensile loading within the strain range of 0-10%, the frequency range of 0.01-10 Hz, to up to 2000 cycles. The potential of the wire senor as wearable strain sensor is demonstrated by the finger motion and blood pulse monitoring. Featured by the low costs of cotton wire and PDMS resin, the simple structure and fabrication technique, as well as high performance with miniaturized size, the wire-shaped sensor based on CT/PDMS composite is believed to have a great potential for application in wearable electronics for human health and motion monitoring.
Yih-Shou Hsieh 1, 2 and Shun-Fa Yang 1,3 and Gautam Sethi 4 and Dan-Ning Hu 5 1, Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan 2, Institute of ...Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan 3, Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan 4, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 119077, Singapore 5, Tissue Culture Center, New York Eye and Ear Infirmary, New York Medical College, New York, NY 10009, USA Received 18 December 2014; Accepted 18 December 2014; 26 March 2015 This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Highlights
The common performance optimization strategies of smart composite hydrogel are summarized.
The recent advanced progress of smart composite hydrogel-based wearable sensors is systematically ...discussed from the aspect of health monitoring.
The current challenges and future prospects of smart composite hydrogel-based wearable sensors are presented.
Growing health awareness triggers the public’s concern about health problems. People want a timely and comprehensive picture of their condition without frequent trips to the hospital for costly and cumbersome general check-ups. The wearable technique provides a continuous measurement method for health monitoring by tracking a person’s physiological data and analyzing it locally or remotely. During the health monitoring process, different kinds of sensors convert physiological signals into electrical or optical signals that can be recorded and transmitted, consequently playing a crucial role in wearable techniques. Wearable application scenarios usually require sensors to possess excellent flexibility and stretchability. Thus, designing flexible and stretchable sensors with reliable performance is the key to wearable technology. Smart composite hydrogels, which have tunable electrical properties, mechanical properties, biocompatibility, and multi-stimulus sensitivity, are one of the best sensitive materials for wearable health monitoring. This review summarizes the common synthetic and performance optimization strategies of smart composite hydrogels and focuses on the current application of smart composite hydrogels in the field of wearable health monitoring.
PDF
