Inkjet-printed morphogenesis of tumor-stroma interface using bi-cellular bioinks of collagen-poly(N-isopropyl acrylamide-co-methyl methacrylate) mixture
Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named "inkjet-printed morphogenesis" (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of "morphogenetic printing" is demonstrated to create more complex structures beyond current 3D bioprinting techniques.
Resolving protein-mineral interfacial interactions during mineralization by atom probe tomography
Organic macromolecules exert remarkable control over the nucleation and growth of inorganic crystallites during (bio)mineralization, as exemplified during enamel formation where the protein amelogenin regulates the formation of hydroxyapatite (HAP). However, it is poorly understood how fundamental processes at the organic-inorganic interface, such as protein adsorption and/or incorporation into minerals, regulates nucleation and crystal growth due to technical challenges in observing and characterizing mineral-bound organics at high-resolution. Here, atom probe tomography techniques were developed and applied to characterize amelogenin-mineralized HAP particles , revealing distinct organic-inorganic interfacial structures and processes at the nanoscale. Specifically, visualization of amelogenin across the mineralized particulate demonstrates protein can become entrapped during HAP crystal aggregation and fusion. Identification of protein signatures and structural interpretations were further supported by standards analyses, i.e., defined HAP surfaces with and without amelogenin adsorbed. These findings represent a significant advance in the characterization of interfacial structures and, more so, interpretation of fundamental organic-inorganic processes and mechanisms influencing crystal growth. Ultimately, this approach can be broadly applied to inform how potentially unique and diverse organic-inorganic interactions at different stages regulates the growth and evolution of various biominerals.
Silk fibers assisted long-term 3D culture of human primary urinary stem cells via inhibition of senescence-associated genes: Potential use in the assessment of chronic mitochondrial toxicity
Despite being widely applied in drug development, existing models are not suitable to assess chronic mitochondrial toxicity. A novel assay system mimicking in vivo microenvironment for this purpose is urgently needed. The goal of this study is to establish a 3D cell platform as a reliable, sensitive, cost-efficient, and high-throughput assay to predict drug-induced mitochondrial toxicity. We evaluated a long-term culture of human primary urine-derived stem cells (USC) seeded in 3D silk fiber matrix (3D USC-SFM) and further tested chronic mitochondrial toxicity induced by Zalcitabine (ddC, a nucleoside reverse transcriptase inhibitor) as a test drug, compared to USC grown in spheroids. The numbers of USC remain steady in 3D spheroids for 4 weeks and 3D SFM for 6 weeks. However, the majority (95%) of USC survived in 3D SFM, while cell numbers significantly declined in 3D spheroids at 6 weeks. Highly porous SFM provides large-scale numbers of cells by increasing the yield of USC 125-fold/well, which enables the carrying of sufficient cells for multiple experiments with less labor and lower cost, compared to 3D spheroids. The levels of mtDNA content and mitochondrial superoxide dismutase [SOD2] as an oxidative stress biomarker and cell senescence genes (RB and P16, p21) of USC were all stably retained in 3D USC-SFM, while those were significantly increased in spheroids. mtDNA content and mitochondrial mass in both 3D culture models significantly decreased six weeks after treatment of ddC (0.2, 2, and 10 μM), compared to 0.1% DMSO control. Levels of complexes I, II, and III significantly decreased in 3D SFM-USC treated with ddC, compared to only complex I level which declined in spheroids. A dose- and time-dependent chronic MtT displayed in the 3D USC-SFM model, but not in spheroids. Thus, a long-term 3D culture model of human primary USC provides a cost-effective and sensitive approach potential for the assessment of drug-induced chronic mitochondrial toxicity.
Effective antiviral coatings for deactivating SARS-CoV-2 virus on N95 respirator masks or filters
The application of antiviral coatings to masks and respirators is a potential mitigating step toward reducing viral transmission during the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The use of appropriate masks, social distancing, and vaccines is the immediate solution for limiting the viral spread and protecting people from this virus. N95 respirator masks are effective in filtering the virus particles, but they cannot kill or deactivate the virus. We report a possible approach to deactivating SARS-CoV-2 by applying an antimicrobial coating (Goldshield 75) to masks and respirators, rendering them suitable for repeated use. Masks coated with Goldshield 75 demonstrated continuous inactivation of the Alpha and Beta variants of the SARS-CoV-2 over a 3-day period and no loss of inactivation when stored at temperatures at 50 °C.
Calcium carbonate vaterite particles for drug delivery: Advances and challenges
The recent successful application of lipid-based nanoparticles as delivery vehicles in COVID-19 vaccines demonstrated the superior potential of nanoparticle-based technology for targeted drug delivery in biomedicine. Among novel, rapidly advancing delivery platforms, the inorganic nano/microparticles gradually reach new heights and attract well-deserved attention among scientists and clinicians. Calcium carbonate in its vaterite form is used as a biocompatible carrier for a progressively increasing number of biomedical applications. Its growing popularity is conferred by beneficial porosity of particles, high mechanical stability, biodegradability under certain physiological conditions, ability to provide a continuous steady release of bioactives, preferential safety profile, and low cost, which make calcium carbonate a suitable entity of highly efficacious formulations for controlled drug delivery and release. The focal point of the current review is the success of the recent vaterite applications in the delivery of various diagnostics and therapeutic drugs. The manuscript highlights the nuances of drug loading in vaterite particles, connecting it with particle morphology, size, and charge of the loaded molecules, payload concentration, mono- or multiple drug loading. The manuscript also depicts recent successful methods of increasing the loading capacity developed for vaterite carriers. In addition, the review describes the various administration routes for vaterite particles with bioactive payloads, which were reported in recent years. Special attention is given to the multi-drug-loaded vaterite particles ("molecular cocktails") and reports on their successful delivery and .
Potentialities of graphene and its allied derivatives to combat against SARS-CoV-2 infection
Graphene is a two-dimensional material with sp hybridization that has found its broad-spectrum potentialities in various domains like electronics, robotics, aeronautics, etc.; it has recently gained its utilities in the biomedical domain. The unique properties of graphene and its derivatives of graphene have helped them find their utilities in the biomedical domain. Additionally, the sudden outbreak of SARS-CoV-2 has immensely expanded the research field, which has also benefitted graphene and its derivatives. Currently, the world is facing a global pandemic due to the sudden outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as COVID-19, from its major onset in Wuhan city, China, in December 2019. Presently, many new variants and mutants appear, which is more harmful than previous strains. However, researchers and scientists are focused on understanding the target structure of coronavirus, mechanism, causes and transmission mode, treatment, and alternatives to cure these diseases in this critical pandemic situation; many findings are achieved, but much more is unknown and pending to be explored. This review paper is dedicated to exploring the utilities of graphene and its derivatives in combating the SARS-CoV-2 by highlighting their mechanism and applications in the fabrication of biosensors, personal protection equipment (PPE) kits, 3-D printing, and antiviral coatings. Further, the paper also covers the cytotoxicity caused by graphene and its derivatives and highlights the graphene-based derivatives market aspects in biomedical domains. Thus, graphene and graphene-derived materials are our new hope in this pandemic time, and this review helps acquire broad knowledge about them.
SARS-CoV-2 in wastewater: From detection to evaluation
SARS-CoV-2 presence in wastewater has been reported in several studies and has received widespread attention among the Wastewater-based epidemiology (WBE) community. Such studies can potentially be used as a proxy for early warning of potential COVID-19 outbreak, or as a mitigation measure for potential virus transmission via contaminated water. In this review, we summarized the latest understanding on the detection, concentration, and evaluation of SARS-CoV-2 in wastewater. Importantly, we discuss factors affecting the quality of wastewater surveillance ranging from temperature, pH, starting concentration, as well as the presence of chemical pollutants. These factors greatly affect the reliability and comparability of studies reported by various communities across the world. Overall, this review provides a broadly encompassing guidance for epidemiological study using wastewater surveillance.
Materials in advanced design of personal protective equipment: a review
The outbreak of the Covid-19 pandemic has aroused tremendous attention toward personal protective equipment (PPE) in both scientific research and industrial manufacture. Despite decades of development in PPE design and fabrication, there's still much room for further optimization, in terms, of both protection performance and wear comfort. Interdisciplinary efforts have been devoted to this research field in recent years. Significantly, the innovation of materials, which brings about improved performance and versatile new functions for PPEs, has been widely adopted in PPE design. In this minireview, recent progress in the development of novel materials and structural designs for PPE application are presented in detail with the introduction of various material-based strategies for different PPE types, as well as the examples, which apply auxiliary components into face masks to enrich the functionalities and improve the personal feelings in the pandemic period.
Design and development of multilayer cotton masks via machine learning
With the ongoing COVID-19 pandemic, reusable high-performance cloth masks are recommended for the public to minimize virus spread and alleviate the demand for disposable surgical masks. However, the approach to design a high-performance cotton mask is still unclear. In this study, we aimed to find out the relationship between fabric properties and mask performance via experimental design and machine learning. Our work is the first reported work of employing machine learning to develop protective face masks. Here, we analyzed the characteristics of Egyptian cotton (EC) fabrics with different thread counts and measured the efficacy of triple-layered masks with different layer combinations and stacking orders. The filtration efficiencies of the triple-layered masks were related to the cotton properties and the layer combination. Stacking EC fabrics in the order of thread count 100-300-100 provides the best particle filtration efficiency (45.4%) and bacterial filtration efficiency (98.1%). Furthermore, these key performance metrics were correctly predicted using machine-learning models based on the physical characteristics of the constituent EC layers using Lasso and XGBoost machine-learning models. Our work showed that the machine learning-based prediction approach can be generalized to other material design problems to improve the efficiency of product development.
N95 respirator decontamination: a study in reusability
The coronavirus disease 2019 (COVID-19) pandemic had caused a severe depletion of the worldwide supply of N95 respirators. The development of methods to effectively decontaminate N95 respirators while maintaining their integrity is crucial for respirator regeneration and reuse. In this study, we systematically evaluated five respirator decontamination methods using vaporized hydrogen peroxide (VHP) or ultraviolet (254 nm wavelength, UVC) radiation. Through testing the bioburden, filtration, fluid resistance, and fit (shape) of the decontaminated respirators, we found that the decontamination methods using BioQuell VHP, custom VHP container, Steris VHP, and Sterrad VHP effectively inactivated Cardiovirus (3-log reduction) and bacteria (6-log reduction) without compromising the respirator integrity after 2-15 cycles. Hope UVC system was capable of inactivating Cardiovirus (3-log reduction) but exhibited relatively poorer bactericidal activity. These methods are capable of decontaminating 10-1000 respirators per batch with varied decontamination times (10-200 min). Our findings show that N95 respirators treated by the previously mentioned decontamination methods are safe and effective for reuse by industry, laboratories, and hospitals.
Toward the prevention of coronavirus infection: what role can polymers play?
Severe acute respiratory syndrome-associated coronavirus 2 has caused a global public health crisis with high rates of infection and mortality. Treatment and prevention approaches include vaccine development, the design of small-molecule antiviral drugs, and macromolecular neutralizing antibodies. Polymers have been designed for effective virus inhibition and as antiviral drug delivery carriers. This review summarizes recent progress and provides a perspective on polymer-based approaches for the treatment and prevention of coronavirus infection. These polymer-based partners include polyanion/polycations, dendritic polymers, macromolecular prodrugs, and polymeric drug delivery systems that have the potential to significantly improve the efficacy of antiviral therapeutics.
Engineering of biomaterials for tumor modeling
Development of biomaterials mimicking tumor and its microenvironment has recently emerged for the use of drug discovery, precision medicine, and cancer biology. These biomimetic models have developed by reconstituting tumor and stroma cells within the 3D extracellular matrix. The models are recently extended to recapitulate the tumor microenvironment, including biological, chemical, and mechanical conditions tailored for specific cancer type and its microenvironment. In spite of the recent emergence of various innovative engineered tumor models, many of these models are still early stage to be adapted for cancer research. In this article, we review the current status of biomaterials engineering for tumor models considering three main aspects - cellular engineering, matrix engineering, and engineering for microenvironmental conditions. Considering cancer-specific variability in these aspects, our discussion is focused on pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC). In addition, we further discussed the current challenges and future opportunities to create reliable and relevant tumor models.
New frontiers in atom probe tomography: a review of research enabled by cryo and/or vacuum transfer systems
There has been a recent surge in the use of cryo and/or vacuum specimen preparation and transfer systems to broaden the scope of research enabled by the microscopy technique of atom probe tomography. This is driven by the fact that, as for many microscopes, the application of atom probes to air- and temperature-sensitive materials or wet biological specimens has previously been limited by transfer through air at room temperature. Here we provide an overview of areas of research that benefit from these new transfer and analysis protocols, as well as a review of current advances in transfer devices, environmental cells, and glove boxes for controlled specimen manipulation. This includes the study of catalysis and corrosion, biological samples, liquid-solid interfaces, natural aging, and the distribution of hydrogen in materials.