Characterization of human nasal organoids from chronic rhinosinusitis patients.

Patient-derived organoids grown in three-dimensional cultures provide an excellent platform for phenotypic high-throughput screening and drug-response research. Organoid technology has been applied to study stem cell biology and various human pathologies. This study investigates the characteristics and cellular morphology of organoids derived from primary human nasal epithelial cells (HNECs) of chronic rhinosinusitis (CRS) patients. Nasal organoids were cultured up to 20 days and morphological, cell composition and functional parameters were measured by immunofluorescence, RT-qPCR, western blot and FACS analysis. The results showed that nasal organoids expressed the stem cell marker leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), and markers for apical junction genes, goblet cells and ciliated cells. Moreover, we were able to regrow and expand the nasal organoids well after freezing and thawing. This study provides an effective and feasible method for development of human nasal organoids, suitable for the phenotypic high-throughput screening and drug response research.

Advancing of 3D-Printed Titanium Implants with Combined Antibacterial Protection Using Ultrasharp Nanostructured Surface and Gallium-Releasing Agents.

This paper presents the development of advanced Ti implants with enhanced antibacterial activity. The implants were engineered using additive manufacturing three-dimensional (3D) printing technology followed by surface modification with electrochemical anodization and hydrothermal etching, to create unique hierarchical micro/nanosurface topographies of microspheres covered with sharp nanopillars that can mechanically kill bacteria in contact with the surface. To achieve enhanced antibacterial performance, fabricated Ti implant models were loaded with gallium nitrate as an antibacterial agent. The antibacterial efficacy of the fabricated substrates with the combined action of sharp nanopillars and locally releasing gallium ions (Ga3+) was evaluated toward Staphylococcus aureus and Pseudomonas aeruginosa. Results confirm the significant antibacterial performance of Ga3+-loaded substrates with a 100% eradication of bacteria. The nanopillars significantly reduced bacterial attachment and prevented biofilm formation while also killing any bacteria remaining on the surface. Furthermore, 3D-printed surfaces with microspheres of diameter 5-30 µm and interspaces of 12-35 µm favored the attachment of osteoblast-like MG-63 cells, as confirmed via the assessment of their attachment, proliferation, and viability. This study provides important progress toward engineering of next-generation 3D-printed implants, that combine surface chemistry and structure to achieve a highly efficacious antibacterial surface with dual cytocompatibility to overcome the limitations of conventional Ti implants.

Tailoring Additively Manufactured Titanium Implants for Short-Time Pediatric Implantations with Enhanced Bactericidal Activity.

Paediatric titanium (Ti) implants are used for the short-term fixation of fractures, after which they are removed. However, bone overgrowth on the implant surface can complicate their removal. The current Ti implants research focuses on improving their osseointegration and antibacterial properties for long-term use while overlooking the requirements of temporary implants. This paper presents the engineering of additively manufactured Ti implants with antibacterial properties and prevention of bone cell overgrowth. 3D-printed implants were fabricated followed by electrochemical anodization to generate vertically aligned titania nanotubes (TNTs) on the surface with specific diameters (∼100 nm) to reduce cell attachment and proliferation. To achieve enhanced antibacterial performance, TNTs were coated with gallium nitrate as antibacterial agent. The physicochemical characteristics of these implants assessed by the attachment, growth and viability of osteoblastic MG-63 cells showed significantly reduced cell attachment and proliferation, confirming the ability of TNTs surface to avoid cell overgrowth. Gallium coated TNTs showed strong antibacterial activity against S. aureus and P. aeruginosa with reduced bacterial attachment and high rates of bacterial death. Thus a new approach for the engineering of temporary Ti implants with enhanced bactericidal properties with reduced bone cell attachment is demonstrated as a new strategy toward a new generation of short-term implants in paediatrics.

Fractal Design for Advancing the Performance of Chemoresistive Sensors.

The rapid advancement of internet of things (IoT)-enabled applications along with connected automation in sensing technologies is the heart of future intelligent systems. The probable applications have significant implications, from chemical process monitoring to agriculture, mining, space, wearable electronics, industrial manufacturing, smart cities, and point-of-care (PoC) diagnostics. Advancing sensor performance such as sensitivity to detect trace amounts (ppb-ppm) of analytes (gas/VOCs), selectivity, portability, and low cost is critical for many of these applications. These advancements are mainly achieved by selecting and optimizing sensing materials by their surface functionalization and/or structural optimization to achieve favorable transport characteristics or chemical binding/reaction sites. Surprisingly, the sensor geometry, shapes, and patterns were not considered as critical parameters, and most of these sensors were designed by following simple planar and interdigitated electrode geometry. In this study, we introduce a new bioinspired fractal approach to design chemoresistive sensors with fractal geometry, which grasp the architecture of fern leaves represented by the geometric group of space-filling curves of fractal patterns. These fractal sensors were printed by an extrusion process on a flexible substrate (PET) using specially formulated graphene ink as a sensing material, which provided significant enhancement of the active surface area to volume ratio and allowed high-resolution fractal patterning along with a reduced current transportation path. To demonstrate the advantages and influence of fractal geometry on sensor performance, here, three different kinds of sensors were fabricated based on different fractal geometrics (Sierpinski, Peano, and Hilbert), and the sensing performance was explored toward different VOC analytes (e.g., ethanol, methanol, and acetone). Among all these fractal-designed sensors including interdigitate sensors, the Hilbert-designed printed sensor shows enhanced sensing properties in terms of fast response time (6 s for 30 ppm), response value (14%), enhanced detection range (5-100 ppm), high selectivity, and low interference to humidity (up to RH 80%) for ethanol at room temperature (20 °C). Moreover, a significant improvement of this sensor performance was observed by applying the mechanical deformation (positive bending) technique. The practical application of this sensor was successfully demonstrated by monitoring food spoilage using a commercial box of strawberries as a model. Based on these presented results, this biofractal biomimetic VOC sensor is demonstrated for a prospective application in food monitoring.

Converging 2D Nanomaterials and 3D Bioprinting Technology: State-of-the-Art, Challenges, and Potential Outlook in Biomedical Applications.

The development of next-generation of bioinks aims to fabricate anatomical size 3D scaffold with high printability and biocompatibility. Along with the progress in 3D bioprinting, 2D nanomaterials (2D NMs) prove to be emerging frontiers in the development of advanced materials owing to their extraordinary properties. Harnessing the properties of 2D NMs in 3D bioprinting technologies can revolutionize the development of bioinks by endowing new functionalities to the current bioinks. First the main contributions of 2D NMS in 3D bioprinting technologies are categorized here into six main classes: 1) reinforcement effect, 2) delivery of bioactive molecules, 3) improved electrical conductivity, 4) enhanced tissue formation, 5) photothermal effect, 6) and stronger antibacterial properties. Next, the recent advances in the use of each certain 2D NMs (1) graphene, 2) nanosilicate, 3) black phosphorus, 4) MXene, 5) transition metal dichalcogenides, 6) hexagonal boron nitride, and 7) metal-organic frameworks) in 3D bioprinting technology are critically summarized and evaluated thoroughly. Third, the role of physicochemical properties of 2D NMSs on their cytotoxicity is uncovered, with several representative examples of each studied 2D NMs. Finally, current challenges, opportunities, and outlook for the development of nanocomposite bioinks are discussed thoroughly.

Comparative antibacterial activity of 2D materials coated on porous-titania.

Plasma electrolytic oxidation (PEO) is a well-established technique for the treatment of titanium-based materials. The formed titania-PEO surface can improve the osseointegration properties of titanium implants. Nevertheless, it can not address bacterial infection problems associated with bone implants. Recently, 2-dimensional (2D) materials such as graphene oxide (GO), MXene, and hexagonal boron nitride (hBN) have received considerable attention for surface modifications showing their antibacterial properties. In this paper, a comparative study on the effect of partial deposition of these three materials over PEO titania substrates on the antibacterial efficiency and bioactivity is presented. Their partial deposition through drop-casting instead of continuous film coating is propsed to simultaneously address both antibacterial and osseointegration abilities. Our results demonstrate the dose-dependent nature of the deposited antibacterial agent on the PEO substrate. GO-PEO and MXene-PEO samples showed the highest antibacterial activity with 70 (±2) % and 97 (±0.5) % inactivation of S. aureus colonies in the low concentration group, respectively. Furthermore, only samples in the higher concentration group were effective against E. coli bacteria with 18 (±2) % and 17 (±4) % decrease in numbers of colonies for hBN-PEO and GO-PEO samples, respectively. Moreover, all antibacterial samples demonstrated acceptable bioactivity and good biocompatibility, making them a considerable candidates for the next generation of antibacterial titanium implants.

3D bioprinting of a cell-laden antibacterial polysaccharide hydrogel composite.

Bioink with inherent antibacterial activity is of particular interest for tissue engineering application due to the growing number of bacterial infections associated with impaired wound healing or bone implants. However, the development of cell-laden bioink with potent antibacterial activity while supporting tissue regeneration proved to be challenging. Here, we introduced a cell-laden antibacterial bioink based on Methylcellulose/Alginate (MC/Alg) hydrogel for skin tissue engineering via elimination of the risks associated with a bacterial infection. The key feature of the bioink is the use of gallium (Ga+3) in the design of bioink formulation with dual functions. First, Ga+3 stabilized the hydrogel bioink by the formation of ionic crosslinking with Alg chains. Second, the gallium-crosslinked bioink exhibited potent antibacterial activity toward both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with a bactericidal rate of 99.99 %. In addition, it was found that the developed bioink supported encapsulated fibroblast cellular functions.

Graphene ink for 3D extrusion micro printing of chemo-resistive sensing devices for volatile organic compound detection.

Printed electronic sensors offer a breakthrough in the availability of low-cost sensor devices for improving the quality of human life. Conductive ink is the core of printing technology and also one of the fastest growing sector among all ink industries. Among many developed conductive inks, graphene-based inks are especially recognized as very promising for future fabrication of devices due to their low cost, unique properties, and compatibility with various platforms such as plastics, textiles, and paper. The development of graphene ink formulations for achieving high conductivity and high resolution printing is highly realized in 2D inkjet printing. Unfortunately, the ongoing development of graphene inks is possibly hampered by the non-uniform particle size and structures (e.g., different shapes and number of layers), which adversely affect printing resolution, conductivity, adhesion, and structural integrity. This study presents an environmentally sustainable route to produce graphene inks specifically designed for 3D extrusion-printing. The application of the prepared ink is demonstrated by mask-free automatic patterning of sensing devices for the detection of volatile organic compounds (VOCs). The sensing devices fabricated with this new ink display high-resolution patterning (average height/thickness of ∼12 µm) and a 10-fold improvement in the surface area/volume (SA/V) ratio compared to a conventional drop casting method. The extrusion printed sensors show enhanced sensing characteristics in terms of sensitivity and selectivity towards trace amount of VOC (e.g. 5 ppm ethanol) at room temperature (20 °C), which highlights that our method has highly promising potential in graphene printing technology for sensing applications.

Functional inks and extrusion-based 3D printing of 2D materials: a review of current research and applications.

Graphene and related 2D materials offer an ideal platform for next generation disruptive technologies and in particular the potential to produce printed electronic devices with low cost and high throughput. Interest in the use of 2D materials to create functional inks has exponentially increased in recent years with the development of new ink formulations linked with effective printing techniques, including screen, gravure, inkjet and extrusion-based printing towards low-cost device manufacturing. Exfoliated, solution-processed 2D materials formulated into inks permits additive patterning onto both rigid and conformable substrates for printed device design with high-speed, large-scale and cost-effective manufacturing. Each printing technique has some sort of clear advantages over others that requires characteristic ink formulations according to their individual operational principles. Among them, the extrusion-based 3D printing technique has attracted heightened interest due to its ability to create three-dimensional (3D) architectures with increased surface area facilitating the design of a new generation of 3D devices suitable for a wide variety of applications. There still remain several challenges in the development of 2D material ink technologies for extrusion printing which must be resolved prior to their translation into large-scale device production. This comprehensive review presents the current progress on ink formulations with 2D materials and their broad practical applications for printed energy storage devices and sensors. Finally, an outline of the challenges and outlook for extrusion-based 3D printing inks and their place in the future printed devices ecosystem is presented.

Flame Retardancy of Bio-Based Polyurethanes: Opportunities and Challenges.

Sustainable polymers are emerging fast and have received much more attention in recent years compared to petro-sourced polymers. However, they inherently have low-quality properties, such as poor mechanical properties, and inadequate performance, such as high flammability. In general, two methods have been considered to tackle such drawbacks: (i) reinforcement of sustainable polymers with additives; and (ii) modification of chemical structure by architectural manipulation so as to modify polymers for advanced applications. Development and management of bio-based polyurethanes with flame-retardant properties have been at the core of attention in recent years. Bio-based polyurethanes are currently prepared from renewable, bio-based sources such as vegetable oils. They are used in a wide range of applications including coatings and foams. However, they are highly flammable, and their further development is dependent on their flame retardancy. The aim of the present review is to investigate recent advances in the development of flame-retardant bio-based polyurethanes. Chemical structures of bio-based flame-retardant polyurethanes have been studied and explained from the point of view of flame retardancy. Moreover, various strategies for improving the flame retardancy of bio-based polyurethanes as well as reactive and additive flame-retardant solutions are discussed.

3D bioprinting of cell-laden electroconductive MXene nanocomposite bioinks.

MXenes, a new family of burgeoning two-dimensional (2D) transition metal carbides/nitrides, have been extensively explored in recent years owing to their outstanding properties such as a large specific surface area, high electrical conductivity, low toxicity, and biodegradability. Numerous efforts have been devoted to exploring MXenes for various biomedical applications such as cancer therapy, bioimaging, biosensing, and drug delivery. However, the potential application of MXene nanosheets in tissue engineering has been almost overlooked despite their excellent performance in other biomedical applications. The overarching goal of this paper is to demonstrate the potential of MXene cell-laden bioinks for tissue engineering and their ability to assemble functional scaffolds to regenerate damaged tissue via 3D bioprinting. We formulate a new electroconductive cell-laden bioink composed of Ti3C2 MXene nanosheets dispersed homogeneously within hyaluronic acid/alginate (HA/Alg) hydrogels and showed its performance for extrusion-based 3D bioprinting. The prepared hydrogel bioinks with MXenes display excellent rheological properties, which allows the fabrication of multilayered 3D structures with high resolution and shape retention. Moreover, the introduction of Ti3C2 MXene nanosheets within the HA/Alg hydrogel introduces electrical conductivity to the ink, addressing the poor electrical conductivity of the current bioinks that mismatch with the physico-chemical properties of tissue. In addition, the MXene nanocomposite ink with encapsulated Human Embryonic Kidney 293 (HEK-293) cells displayed high cell viability (>95%) in both bulk hydrogel and 3D bioprinted structures. These results suggest that MXene nanocomposite bioinks and their 3D bioprinting with high electrical conductivity, biocompatibility and degradability can synergize some new applications for tissue and neural engineering.

3D printing of cell-laden electroconductive bioinks for tissue engineering applications.

Bioprinting is an emerging powerful fabrication method, which enables the rapid assembly of 3D bioconstructs with dispensing cell-laden bioinks in pre-designed locations. However, to translate this technology into real applications, there are still a number of challenges that need to be addressed. First, the current inks are generally composed of polymeric materials with poor electrical conductivity that mismatches with the native tissue environment. The second challenge associated with the 3D bioprinting of hydrogel-based bioinks is the fabrication of anatomical-size constructs without any loss of shape fidelity and resolution. To address these challenges, in this work, we introduced a biocompatible bioink associated with current 3D bioprinting by combining methylcellulose and kappa-carrageenan (MC/κCA) hydrogels with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) conducting polymers. The prepared ink exhibited highly thixotropic behaviour, which could be tuned via changing the concentration of MC and κCA to obtain easy printing with high shape fidelity. The ink was able to fabricate physiological-scale constructs without requiring a secondary support bath. In addition, varying the concentration of PEDOT:PSS could control the electrical conductivity of the ink. Moreover, the encapsulated human embryonic kidney 293 (HEK-293) cells in bulk hydrogels and 3D bioprinted structures maintained high cell viability (>96%) over a week, confirming the in vitro biocompatibility of the ink. Overall, these findings indicate that the MC/κCA/PEDOT:PSS bioink can be promising in biomedical applications, which improved the electroconductivity of bioinks and can exploit the advantage of conductive polymers in the 3D bioprinting technology.

3D Bioprinting of Methylcellulose/Gelatin-Methacryloyl (MC/GelMA) Bioink with High Shape Integrity.

The advent of three-dimensional (3D) bioprinting offers a feasible approach to construct complex structures suitable for tissue regeneration, during which cell-laden materials are dispensed on a substrate according to a predesigned structure. However, the lack of ideal printable bioinks with high shape fidelity and improved biological stability remains a major challenge. In this study, methylcellulose/gelatin-methacryloyl (MC/GelMA) bioink with high shape integrity is presented, which takes advantage of the printability of MC and the permanent photo-cross-linking of GelMA under UV irradiation. Although MC demonstrates good printability at room temperature, the lack of cross-linking ability causes distortion and finally dissociation of printed MC in biological media within a few days. However, UV-cross-linked MC/GelMA bioink remains stable in biological media over a period of several months. The shape integrity of MC/GelMA was systematically characterized in terms of yield stress and complex modulus. Unlike pure MC ink, the MC/GelMA ink demonstrated self-supporting behavior once printed due to the higher complex modulus and yield stress induced by GelMA in the system. Shape integrity of MC/GelMA ink resulted in higher resolution and printability which are evaluated by the successful printing of various 1D, 2D, and 3D constructs. Moreover, human primary osteoblasts encapsulated within the MC/GelMA hydrogel show cell viability of >95%. Overall, this work introduces MC/GelMA bioink with high shape integrity and improved biological stability and highlights the importance of rheological properties and post-cross-linking for fabrication of physiologically scaled tissue implants.