Human nasal epithelial cells (hNECs) are an essential cell source for the reconstruction of the respiratory pseudostratified columnar epithelium composed of multiple cell types in the context of ...infection studies and disease modeling. Hitherto, manual seeding has been the dominant method for creating nasal epithelial tissue models. However, the manual approach is slow, low-throughput and has limitations in terms of achieving the intricate 3D structure of the natural nasal epithelium in a uniform manner. 3D Bioprinting has been utilized to reconstruct various epithelial tissue models, such as cutaneous, intestinal, alveolar, and bronchial epithelium, but there has been no attempt to use of 3D bioprinting technologies for reconstruction of the nasal epithelium. In this study, for the first time, we demonstrate the reconstruction of the nasal epithelium with the use of primary hNECs deposited on Transwell inserts via droplet-based bioprinting (DBB), which enabled high-throughput fabrication of the nasal epithelium in Transwell inserts of 24-well plates. DBB of nasal progenitor cells ranging from one-tenth to one-half of the cell seeding density employed during the conventional cell seeding approach enabled a high degree of differentiation with the presence of cilia and tight-junctions over a 4-week air-liquid interface culture. Single cell RNA sequencing of these cultures identified five major epithelial cells populations, including basal, suprabasal, goblet, club, and ciliated cells. These cultures recapitulated the pseudostratified columnar epithelial architecture present in the native nasal epithelium and were permissive to respiratory virus infection. These results denote the potential of 3D bioprinting for high-throughput fabrication of nasal epithelial tissue models not only for infection studies but also for other purposes such as disease modeling, immunological studies, and drug screening.
Three-dimensional (3D) printing in tissue engineering has been studied for the bio mimicry of the structures of human tissues and organs. Now, it is being applied to 3D cell printing, which can ...position cells and biomaterials, such as growth factors, at desired positions in the 3D space. However, there are some challenges of 3D cell printing, such as cell damage during the printing process and the inability to produce a porous 3D shape owing to the embedding of cells in the hydrogel-based printing ink, which should be biocompatible, biodegradable, and non-toxic, etc. Therefore, researchers have been studying ways to balance or enhance the post-print cell viability and the print-ability of 3D cell printing technologies by accommodating several mechanical, electrical, and chemical based systems. In this mini-review, several common 3D cell printing methods and their modified applications are introduced for overcoming deficiencies of the cell printing process.
Gene therapeutic applications combined with bio- and nano-materials have been used to address current shortcomings in bone tissue engineering due to their feasibility, safety and potential capability ...for clinical translation. Delivery of non-viral vectors can be altered using gene-activated matrices to improve their efficacy to repair bone defects.Ex-situandin-situdelivery strategies are the most used methods for bone therapy, which have never been directly compared for their potency to repair critical-sized bone defects. In this regard, we first time explore the delivery of polyethylenimine (PEI) complexed plasmid DNA encoding bone morphogenetic protein-2 (PEI-pBMP-2) using the two delivery strategies,ex-situandin-situdelivery. To realize these gene delivery strategies, we employed intraoperative bioprinting (IOB), enabling us to 3D bioprint bone tissue constructs directly into defect sites in a surgical setting. Here, we demonstrated IOB of an osteogenic bioink loaded with PEI-pBMP-2 for thein-situdelivery approach, and PEI-pBMP-2 transfected rat bone marrow mesenchymal stem cells laden bioink for theex-situdelivery approach as alternative delivery strategies. We found thatin-situdelivery of PEI-pBMP-2 significantly improved bone tissue formation compared toex-situdelivery. Despite debates amongst individual advantages and disadvantages ofex-situandin-situdelivery strategies, our results ruled in favor of thein-situdelivery strategy, which could be desirable to use for future clinical applications.
Cellulose has been widely used as micro/nanofibers in various applications of tissue regeneration, but has certain limitations for bone regeneration,
e.g.
, low biocompatibility in inducing ...osteogenesis. In addition, the low processability from the decomposition property before melting can be a significant obstacle to fabricating a required complex structure through a 3D-printing process. Herein, to overcome the low osteogenic activity of pure cellulose, we suggest a new cellulose-based composite scaffold consisting of cellulose and a high weight fraction (70 wt%) of calcium-deficient-hydroxyapatite (CDHA), which was obtained from the hydrolysis of α-tricalcium phosphate. Using biocompatible components, we fabricated a 3D pore-structure controllable composite scaffold consisting of microfibrous bundles through an electrohydrodynamic printing (EHDP) process supplemented with an ethanol bath. To obtain a mechanically stable and repeatable 3D mesh structure, various process parameters (nozzle-to-target distance, electric field strength, flow rate, and nozzle moving speed) were considered. As a control, a mesh structure fabricated using a normal EHDP process and with a similar pore geometry was used. A variety of cellular responses using preosteoblasts (MC3T3-E1) indicate that a CDHA/cellulose composite scaffold provides an efficient platform for inducing significantly high bone mineralization.
The fabricated ceramic scaffold showed a layer-by-layered mesh structure entangled with cellulose micro/nanofibers and the bioceramic phase. By varying processing parameters, the unique 3D fibrous mesh-structure could be achieved.
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IJS, KILJ, NUK, UL, UM, UPUK
In this research, we present the robust reliability performance of BEOL by utilizing EUV single patterning and further feasibility of EUV process for future nodes. As compared to ArF, EUV BEOL shows ...superior reliability performances such as significantly improved TDDB, breakdown voltage (Vbd), robust resistance shift with SM and TC tests and reliable package level characteristics. Long-term TDDB analysis follows an even more aggressive power law model rather than the root E model under low bias. Newly developed via array (quasi-power rail) EM structure has a great feasibility to enhance EM performance for future nodes.
In this study, intuitive is given on time-dependent thermal characteristics in multilevel interconnects subjected to carry either DC or pulsed-DC. FEM simulation is employed to model the propensity ...of temperature profile with respect to the variety of interconnects having different geometrical features in terms of metal width, metal height and distance between metal and Si substrate. Accordingly, a practical model that enables to prognosis temperature increase resulting from current-driven metal interconnects and temperature decrease after current carried along metal line stops is developed. It is found that a proposed model precisely predicts thermal transient arisen from metal interconnect, regardless of geometrical factors of metal dimension and location. In addition, transient thermal behavior of metal interconnects carrying pulsed DC with various frequencies is investigated. A circuit designer is required to adjust the maximum allowable current carried along metal interconnects according to the frequency of pulsed DC as well as geometrical dimensions of metal interconnects. Hence, robustness in circuit design even in the earlier stage of development phase can be accomplished for metal interconnects by suppressing electromigration and rupture caused by thermal transient.
In this paper, we will report the reliability characterization of advanced FinFET technology which is developed by utilizing EUV. The intrinsic device reliability including HCI, BTI, and TDDB is ...comparable across FinFET technologies, and would not be degraded by scaling down. The use of EUV single patterning significantly improves reliability variation so that improved reliability lifetime compared to the use of ArF multi-patterning. Also, the fact that long-term reliability results support lifetime projection of TDDB follows power model, enables us to utilize more reliability margins in the scaled FinFET technologies.
During the past decades, FinFET has been the main device architecture to accelerate transistor performance. Since FinFET should be scaled down with multi-function replace metal gate (RMG) and narrow ...and taller fin shape, the reliability issues have been concerned as well. It is very important to address the current reliability consideration on evolutionary FinFET and would be helpful to consider the new device architecture like gate all around device beyond FinFET. The baseline reliability on gate dielectric TDDB and BTI is less impacted by work-function modulation for scaled FinFET. In order to meet the wide range of Vt, the additional dipole is utilized resulting in TDDB improvement. The self-heating effect (SHE) should be considered for the intrinsic reliability with very narrower vertical fin structure. The layout dependent self-heating characterization and its model are presented. The BEOL electro-migration needs to add the transistor level self-heating in the thermal aware EM model. Since MOL and BEOL pitch is aggressive reduced, the intrinsic reliability and extrinsic reliability should be considered at the same time. For the high-volume products, the extrinsic failures should be suppressed below ppm level. Since the physical spacing all across the critical is very close to direct tunneling regime, the TTF based reliability model should be considered with power law for FEOL, MOL and BEOL for FinFET technology and beyond.
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