Nanomaterials in 4D Printing: Expanding the Frontiers of Advanced Manufacturing.

As an innovative technology, four-dimentional (4D) printing is built upon the principles of three-dimentional (3D) printing with an additional dimension: time. While traditional 3D printing creates static objects, 4D printing generates "responsive 3D printed structures", enabling them to transform or self-assemble in response to external stimuli. Due to the dynamic nature, 4D printing has demonstrated tremendous potential in a range of industries, encompassing aerospace, healthcare, and intelligent devices. Nanotechnology has gained considerable attention owing to the exceptional properties and functions of nanomaterials. Incorporating nanomaterials into an intelligent matrix enhances the physiochemical properties of 4D printed constructs, introducing novel functions. This review provides a comprehensive overview of current applications of nanomaterials in 4D printing, exploring their synergistic potential to create dynamic and responsive structures. Nanomaterials play diverse roles as rheology modifiers, mechanical enhancers, function introducers, and more. The overarching goal of this review is to inspire researchers to delve into the vast potential of nanomaterial-enabled 4D printing, propelling advancements in this rapidly evolving field.

Titanium-Based Nanoarchitectures for Sonodynamic Therapy-Involved Multimodal Treatments.

Sonodynamic therapy (SDT) has considerably revolutionized the healthcare sector as a viable noninvasive therapeutic procedure. It employs a combination of low-intensity ultrasound and chemical entities, known as a sonosensitizer, to produce cytotoxic reactive oxygen species (ROS) for cancer and antimicrobial therapies. With nanotechnology, several unique nanoplatforms are introduced as a sonosensitizers, including, titanium-based nanomaterials, thanks to their high biocompatibility, catalytic efficiency, and customizable physicochemical features. Additionally, developing titanium-based sonosensitizers facilitates the integration of SDT with other treatment modalities (for example, chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy), hence increasing overall therapeutic results. This review summarizes the most recent developments in cancer therapy and tissue engineering using titanium nanoplatforms mediated SDT. The synthesis strategies and biosafety aspects of Titanium-based nanoplatforms for SDT are also discussed. Finally, various challenges and prospects for its further development and potential clinical translation are highlighted.

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.

Critical signaling pathways governing hepatocellular carcinoma behavior; small molecule-based approaches.

Hepatocellular carcinoma (HCC) is the second leading cause of death due to cancer. Although there are different treatment options, these strategies are not efficient in terms of restricting the tumor cell's proliferation and metastasis. The liver tumor microenvironment contains the non-parenchymal cells with supportive or inhibitory effects on the cancerous phenotype of HCC. Several signaling pathways are dis-regulated in HCC and cause uncontrolled cell propagation, metastasis, and recurrence of liver carcinoma cells. Recent studies have established new approaches for the prevention and treatment of HCC using small molecules. Small molecules are compounds with a low molecular weight that usually inhibit the specific targets in signal transduction pathways. These components can induce cell cycle arrest, apoptosis, block metastasis, and tumor growth. Devising strategies for simultaneously targeting HCC and the non-parenchymal population of the tumor could lead to more relevant research outcomes. These strategies may open new avenues for the treatment of HCC with minimal cytotoxic effects on healthy cells. This study provides the latest findings on critical signaling pathways governing HCC behavior and using small molecules in the control of HCC both in vitro and in vivo models.

On-Chip Concentration and Patterning of Biological Cells Using Interplay of Electrical and Thermal Fields.

We demonstrate a method of concentrating and patterning of biological cells on a chip, exploiting the confluence of electric and thermal fields, without necessitating the use of any external heating or illuminating sources. The technique simply employs two parallel plate electrodes and an insulating layer over the bottom electrode, with a drilled insulating layer for inducing localized variations in the thermal field. A strong induced electric field, in the process, penetrates through the narrow hole and generates highly nonuniform heating, which in turn, results in gradients in electrical properties and induces mobile charges to impose directional fluid flow. The toroidal vortices, induced by secondary electrokinetic forces originating out of temperature-dependent electrical property variations, transport the suspended cells toward a hot-spot site of the chip, for rapid concentrating and patterning into different shaped clusters based on predesigned conditions, without exceeding safe temperature limits that do not result in damage of thermally labile biological samples. We characterize the efficacy of the cell trapping process for two different biological entities, namely, Escherichia coli bacteria and yeast cells. These results have importance toward developing biomedical microdevices for drug discovery, antibiotic resistance assessment, and medical diagnostics.

Compressive stress-induced autophagy promotes invasion of HeLa cells by facilitating protein turnover in vitro.

Metastasis remains the primary cause of cancer mortality. Throughout the process of metastasis, cancer cells experience mechanical forces, which may turn out to be the key towards their migratory, homeostatic and survival characteristics. However, the influence of compressive stress on the underlying mechanism of cancer cell adaptation during metastasis has remained grossly unexplored. In this study, we have investigated whether compressive force induces autophagy in HeLa cells with potential implications in cellular invasiveness. To this end, we have adopted a simple strategy to create the mechanically-compressed tumor microenvironment, in vitro, by applying appropriate compression to agarose-scaffolded HeLa cell-encapsulated alginate beads. Our findings confirm that compression upregulates autophagy, which promotes paxillin turnover and active MMP-2 secretion, leading to enhanced migration of HeLa cells. We further show that autophagy induction by compression is affected by the phosphorylation of p38 MAPKs, a process that is mediated by intact membrane lipid rafts. Identifying the role of such mechanically triggered cellular responses, guiding crucial processes like cell migration, may lead to better understanding of the mechanobiological aspects of metastatic cancer and unveil potential therapeutic targets.

Production and characterization of multifacet exopolysaccharide from an agricultural isolate, Bacillus subtilis.

This study aims to explore the fermentative production and physicochemical properties of an exopolysaccharide (EPS) produced from agricultural isolate, Bacillus subtilis S1 in submerged culture. The structural characterization (Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and 13 C Nuclear magnetic resonance spectrometry) revealed that the EPS is an acidic heteropolymer consisting of glucose, glucuronic acid, pyruvic acid, and succinic acid. The non-Newtonian shear thickening nature of EPS with a 1.55 × 107  Da molecular weight is confirmed by rheology analysis. The extracted EPS was 61.3% amorphous with partial crystallinity (38.7%) as confirmed by X-ray diffraction analysis. The EPS shows two-step decomposition and thermal stability up to 300 °C as confirmed by thermogravimetric analysis and differential scanning calorimetry analysis. The EPS has a small Z-average particle size (74.29 nm), high porosity (92.99%), high water holding (92.39%), and absorption capacity (1,198%). The biocompatible nature is confirmed by cytotoxic testing on the human keratinocytes cell line. The demonstrated unique characteristics of Bacillus EPS presents it as a choice of biomaterial for diverse applications.

Quorum sensing inhibitory activity of the metabolome from endophytic Kwoniella sp. PY016: characterization and hybrid model-based optimization.

Quorum sensing, the microbial communication system, is gaining importance as a therapeutic target against pathogens. The two key reasons for the rising demand of quorum sensing (QS) inhibitory molecules are low selective pressure to develop resistance by pathogens and possibility of more species-specific effects. Due to complex interactions in a unique niche of live plant tissues, endophytes, as a survival mechanism, potentially produce various bioactive compounds such as QS inhibitors. We report the isolation of an endophytic fungus Kwoniella sp. PY016 from the medicinal plant "Bahera" (Terminalia bellirica), which exhibits substantial quorum sensing inhibition and anti-biofilm activities against the standard test organism, Chromobacterium violaceum. Sugar, sugar alcohol, carboxylic acid, lipid, and phenolic classes of metabolites (predominantly xylitol) are responsible components of the metabolome for the desired bioactivity. A judicious combination of single-factor-at-a-time strategy and artificial neural network modeling combined with genetic algorithm was employed for the selection and optimization of the critical process and medium parameters. Through this newly adopted hybrid model-based optimization, the quorum sensing inhibitory activity of the endophytic metabolome was increased by ~ 30%. This is the first report on optimization of QS inhibitory activity from any fungal endophyte using such a hybrid advanced approach.

Molecular Mechanisms Associated With Particulate and Soluble Heteroglycan Mediated Immune Response.

Immune responses are outcomes of complex molecular machinery which occur inside the cells. Unravelling the cellular mechanisms induced by immune stimulating molecules such as glycans and determining their structure-function relationship are therefore important factors to be assessed. With this viewpoint, the present study identifies the functional receptor binding unit of a well characterized heteroglycan and also delineates the cellular and molecular processes that are induced upon heteroglycan binding to specific cell surface receptors in immune cells. The heteroglycan was acid hydrolysed and it was revealed that 10-30 kDa fractions served as the functional receptor binding unit of the molecule. Increasing the size of 10-30 kDa heteroglycan showed prominent immune activity. The whole soluble heteroglycan was also conjugated with hyperbranched dendrimers so as to generate a particulate form of the molecule. Dectin-1 and TLR2 were identified as the major receptors in macrophages that bind to particulate as well as soluble form of the heteroglycan and subsequently caused downstream signaling molecules such as NF-κß and MAPK to get activated. High levels of 1L-1ß and IL-10 mRNA were observed in particulate heteroglycan treated macrophages, signifying that increasing the size and availability of the heteroglycan to its specific receptors is pertinent to its biological functioning. Upregulated expression of PKC and iNOS were also noted in particulate heteroglycan treated RAW 264.7 cells than the soluble forms. Taken together, our results indicate that biological functions of immunomodulatory heteroglycan are dependent on their size and molecular weight. J. Cell. Biochem. 117: 1580-1593, 2016. © 2015 Wiley Periodicals, Inc.

Chemically enhanced double-gate bilayer graphene field-effect transistor with neutral channel for logic applications.

In this article, we present the simulation, fabrication, and characterization of a novel bilayer graphene field-effect transistor exhibiting electron mobility up to ~1600 cm(2) V(-1) s(-1), a room temperature I on/I off ≈ 60, and the lowest total charge (~10(11) cm(-2)) reported to date. This is achieved by combined electrostatic and chemical doping of bilayer graphene, which enables one to switch off the device at zero top-gate voltage. Using density functional theory and atomistic simulations, we obtain physical insight into the impact of chemical and electrostatic doping on bandgap opening of bilayer graphene and the effect of metal contacts on the operation of the device. Our results represent a step forward in the use of bilayer graphene for high-performance logic devices in the beyond-complementary metal-oxide-semiconductor (CMOS) technology paradigm.

A CFD-based approach to study the deposition and distribution behaviour of 212Pb in a calibration chamber.

Among the several aspects of decay products behavior, deposition is of special significance because of its prominent role in the activity removal from the environment, which eventually results in the occurrence of decay product disequilibrium with the parent gas. This point is particularly important in case of thoron dosimetry where thoron progeny 212Pb accounts for the most of the radiological dose. The deposition depends on the size distribution of decay products and the structure of air turbulence at the air-surface interface. In the present work, the effect of varying air-flow (fan speed) and aerosol count median diameter (CMD) was studied on the deposition and distribution profile of 212Pb using computational fluid dynamics (CFD). The simulations have been carried out in a cubical calibration chamber of volume 8 m3, facilitated at RP&AD, BARC. Simulated results showed that the increase of total depositional loss rate of attached fraction of 212Pb due to increase of the fan speed was significant for CMD up to 400 nm, beyond which this effect started becoming less prominent with increasing diameter. Besides, a minimum of the total depositional loss rate curve was seen to be shifted to the higher CMD with increase of the fan speed. CFD results were found to be in good agreement with experimental observations obtained in the controlled conditions with thoron source.

Bioengineering liver microtissues for modeling non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) has become the world's most common chronic liver disease. However, due to the lack of reliable in vitro NAFLD models, drug development studies have faced many limitations, and there is no food and drug administration-approved medicine for NAFLD treatment. A functional biomimetic in vitro human liver model requires an optimized natural microenvironment using appropriate cellular composition, to provide constructive cell-cell interactions, and niche-specific bio-molecules to supply crucial cues as cell-matrix interplay. Such a suitable liver model could employ appropriate and desired biochemical, mechanical, and physical properties similar to native tissue. Moreover, bioengineered three-dimensional tissues, specially microtissues and organoids, and more recently using infusion-based cultivation systems such as microfluidics can mimic natural tissue conditions and facilitate the exchange of nutrients and soluble factors to improve physiological function in the in vitro generated constructs. This review highlights the key players involved in NAFLD initiation and progression and discussed the available cells and matrices for in vitro NAFLD modeling. The strategies for optimizing the liver microenvironment to generate a powerful and biomimetic in vitro NAFLD model were described as well. Finally, the current challenges and future perospective for promotion in this subject were discussed.

Commercially Available Textiles as a Scaffolding Platform for Large-Scale Cell Culture.

The present study outlines the evaluation of textile materials that are currently in the market for cell culture applications. By using normal LaserJet printing techniques, we created the substrates, which were then characterized physicochemically and biologically. In particular, (i) we found that the weave pattern and (ii) the chemical nature of the textiles significantly influenced the behaviour of the cells. Textiles with closely knitted fibers and cell adhesion motifs, exhibited better cell adhesion and proliferation over a period of 7 days. All the substrates supported good viability of cells (>80%). We believe that these aspects make commercially available textiles as a potential candidate for large-scale culture of adherent cells.

Developed Bone Biomaterials Incorporated with MicroRNAs to Promote Bone Regeneration: A Systematic Review, Bioinformatics, and Meta-analysis Study.

This systematic review and meta-analysis focused on the effectiveness of biomaterials integrated with specific microRNAs (miRNAs) for bone fracture repair treatment. We conducted a comprehensive search of the PubMed, Web of Science, and Scopus databases, identifying 42 relevant papers up to March 2022. Hydrogel-based scaffolds were the most commonly used, incorporating miRNAs like miR-26a, miR-21, and miR-222, with miR-26a being the most prevalent. The meta-analysis revealed significant benefits of incorporating miRNAs into scaffolds for bone repair, particularly in hydrogel scaffolds. However, some controversies were observed among studies, presenting challenges in selecting appropriate miRNAs for this purpose. The study concludes that incorporating specific miRNAs into bone biomaterials enhances bone regeneration, but further trials comparing different biomaterials and miRNAs are necessary to validate their potential applications for bone tissue regeneration.

Defect Engineering in Biomedical Sciences.

With the promotion of nanochemistry research, large numbers of nanomaterials have been applied in vivo to produce desirable cytotoxic substances in response to endogenous or exogenous stimuli for achieving disease-specific therapy. However, the performance of nanomaterials is a critical issue that is difficult to improve and optimize under biological conditions. Defect-engineered nanoparticles have become the most researched hot materials in biomedical applications recently due to their excellent physicochemical properties, such as optical properties and redox reaction capabilities. Importantly, the properties of nanomaterials can be easily adjusted by regulating the type and concentration of defects in the nanoparticles without requiring other complex designs. Therefore, this tutorial review focuses on biomedical defect engineering and briefly discusses defect classification, introduction strategies, and characterization techniques. Several representative defective nanomaterials are especially discussed in order to reveal the relationship between defects and properties. A series of disease treatment strategies based on defective engineered nanomaterials are summarized. By summarizing the design and application of defective engineered nanomaterials, a simple but effective methodology is provided for researchers to design and improve the therapeutic effects of nanomaterial-based therapeutic platforms from a materials science perspective.

Chitosan and its derivatives in 3D/4D (bio) printing for tissue engineering and drug delivery applications.

Tissue engineering research has undergone to a revolutionary improvement, thanks to technological advancements, such as the introduction of bioprinting technologies. The ability to develop suitable customized biomaterial inks/bioinks, with excellent printability and ability to promote cell proliferation and function, has a deep impact on such improvements. In this context, printing inks based on chitosan and its derivatives have been instrumental. Thus, the current review aims at providing a comprehensive overview on chitosan-based materials as suitable inks for 3D/4D (bio)printing and their applicability in creating advanced drug delivery platforms and tissue engineered constructs. Furthermore, relevant strategies to improve the mechanical and biological performances of this biomaterial are also highlighted.

A CFD-based approach to optimize operating parameters of a flow-through scintillation cell for measurement of 220Rn in indoor environments.

The measurements and monitoring of 222Rn/220Rn have been of emerging interest in occupational environments particularly in radium/thorium handling facilities and environments with monazite deposits for the inhalation dosimetry. The performance of a flow-through Lucas scintillation cell (LSC) for long run 220Rn measurements, depends upon the exact distribution pattern of 220Rn and its decay products in the LSC which can vary with the design of inlet path and flow rates. In this work, the CFD technique has been used to study the concentration profiles of 220Rn and its decay products in LSC for varying flow rates and inlet needle lengths. The variation of alpha production efficiency (ηα) is computed and analyzed for each case; aiming to select the best operating range of parameters for the optimum performance of LSC for 220Rn measurements. It is seen that LSC can be operated in the flow rate ranging from 0.6 to 1 lpm with inlet needle length varying from 22.5 to 45 mm for improved sensitivity.

Oxygenation therapies for improved wound healing: current trends and technologies.

Degree of oxygenation is one of the important parameters governing various processes, including cell proliferation, angiogenesis, extracellular matrix production, and even combating the microbial burden at the wound site, all of which are essential for tissue function restoration and integrity. Inadequate oxygenation interrupts the normal healing process and delays patient recovery. The present article overviews the role of oxygen in the wound healing process and different oxygenation therapies that have been applied for healing dermal wounds. Furthermore, we critically assessed various challenges and opportunities in the near future for adequate and controlled oxygen delivery at the wounded site with minimal toxicity.