INMdok (Leibniz Institute for New Materials)
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    931 research outputs found

    Discovery of a high-performance phage-derived promoter/repressor system for probiotic lactobacillus engineering

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    Background: The Lactobacillaceae family comprises many species of great importance for the food and healthcare industries, with numerous strains identified as beneficial for humans and used as probiotics. Hence, there is a growing interest in engineering these probiotic bacteria as live biotherapeutics for animals and humans. However, the genetic parts needed to regulate gene expression in these bacteria remain limited compared to model bacteria like E. coli or B. subtilis. To address this deficit, in this study, we selected and tested several bacteriophage-derived genetic parts with the potential to regulate transcription in lactobacilli. Results: We screened genetic parts from 6 different lactobacilli-infecting phages and identified one promoter/repressor system with unprecedented functionality in Lactiplantibacillus plantarum WCFS1. The phage-derived promoter was found to achieve expression levels nearly 9-fold higher than the previously reported strongest promoter in this strain and the repressor was able to almost completely repress this expression by reducing it nearly 500-fold. Conclusions: The new parts and insights gained from their engineering will enhance the genetic programmability of lactobacilli for healthcare and industrial applications

    Biodegradable SPI-based hydrogel for controlled release of nanomedicines: A potential approach against brain tumors recurrence

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    Glioblastoma (GB) is the most common and aggressive brain tumor. The treatment for newly diagnosed glioblastoma is surgical resection of the primary tumor mass, followed by radiotherapy and chemotherapy. However, recurrences frequently occur in proximity to the surgical resection area. In these cases, none of the current therapies is effective. Recently, implantable biomaterials seem to be a promising strategy against GB recurrence. Here, for the first time we combined the tailorable properties of soy-protein hydrogels with the versatility of drug-loaded liposomes to realize a hybrid biomaterial for controlled and sustained nanoparticles release. Hydrogel consisting of 18–20 % w/v soy-protein isolated were fabricated in absence of chemical cross-linkers. They were biodegradable (−10 % and −30 % of weight by hydrolytic and enzymatic degradation, respectively in 3 days), biocompatible (>95 % of cell viability after treatment), and capable of sustained release of intact doxorubicin-loaded liposomes (diffusion coefficient between 10−18 and 10 −19 m2 s−1). A proof-of-concept in a “donut-like” 3D-bioprinted model shows that liposomes released by hydrogels were able to diffuse in a model with a complex extracellular matrix-like network and a 3D structural organization, targeting glioblastoma cells.The combination of nanoparticles' encapsulation capabilities with the hydrogels' structural support and controlled release properties will provide a powerful tool with high clinical relevance that could be applicable for the treatment of other cancers, realizing patient-specific interventions

    Biofunctional Polyacrylamide Hydrogels using Tetrazole-Methylsulfone Comonomer for Thiol Conjugation

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    Biofunctionalized polyacrylamide (PAAm) hydrogels are important 2D substrates for studying cell physics and mechanobiology. In this work, an arylmethylsulfone (MS) comonomer is developed that can be incorporated into PAAm gels under aqueous radical polymerization conditions. The resulting hydrogels show similar properties to unmodified PAAm gels, indicating that the comonomer is incorporated without affecting PAAm physical properties. The MS-containing PAAm hydrogels allow efficient conjugation of thiol derivatized biomolecules and require very low comonomer content (2 mM, 0.18 mol% relative to AAm) and thiol incubation amounts (≥ 0.15 µg per gel) to achieve functional densities that elicit cell responses. Compared to carboxyl-functionalized PAAm hydrogels, a 10-fold lower comonomer concentration and a 10-fold lower ligand feed concentration are sufficient to achieve comparable cell adhesion responses. The new comonomer opens up possibilities for efficient and straightforward biofunctionalization of PAAm hydrogels used in cell biophysical studies

    Recent Advances in Nanoengineering of Electrode-Electrolyte Interfaces to Realize High-Performance Li-Ion Batteries

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    A suitable interface between the electrode and electrolyte is crucial in achieving highly stable electrochemical performance for Li-ion batteries, as facile ionic transport is required. Intriguing research and development have recently been conducted to form a stable interface between the electrode and electrolyte. Therefore, it is essential to investigate emerging knowledge and contextualize it. The nanoengineering of the electrode-electrolyte interface has been actively researched at the electrode/electrolyte and interphase levels. This review presents and summarizes some recent advances aimed at nanoengineering approaches to build a more stable electrode-electrolyte interface and assess the impact of each approach adopted. Furthermore, future perspectives on the feasibility and practicality of each approach will also be reviewed in detail. Finally, this review aids in projecting a more sustainable research pathway for a nanoengineered interphase design between electrode and electrolyte, which is pivotal for high-performance, thermally stable Li-ion batteries

    Low-temperature sintering of Cu@AG microparticles in air for recyclable printed electronics

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    Silver-coated copper microparticles combine the oxidation resistance of silver with the low cost of copper. They are interesting components for printed conductive structures. We studied whether printed films of such particles can be printed and sintered at low temperatures in air to create highly conductive films and whether it is possible to recover the particles from them for recycling. Pastes containing 1.5 μm to 5 μm spheres and 3 μm flakes with L-ascorbic acid were prepared, screen-printed, and treated at temperatures of 110 °C to 300 °C in air. The bulk resistance of films treated below 160 °C were two orders of magnitude higher than that of bulk copper, ρCu, and limited by particle-particle contact resistances. They were reduced by treating the prints at 160 °C to 250 °C, leading to bulk film resistances down to 41ρCu. We demonstrate that the high mobility of silver enables the formation of necks that bridge the copper cores and reduce resistivity in this temperature window. The sintered prints retained their conductivity for at least 6 months. Treatments at higher temperatures in air were detrimental: resistances increased above 250 °C. These temperatures led to dewetting of the silver coating and fast copper oxidation, resulting in a continuously increasing resistance. In a final study, we demonstrated that films treated below 200 °C can be recycled by recovering the metal powder from the printed conductors and that the powder can be printed again

    Spray drying of a zinc complexing agent for inhalation therapy of pulmonary fibrosis

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    Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis

    Engineering Material Properties of Transcription Factor Condensates to Control Gene Expression in Mammalian Cells and Mice

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    Phase separation of biomolecules into condensates is a key mechanism in the spatiotemporal organization of biochemical processes in cells. However, the impact of the material properties of biomolecular condensates on important processes, such as the control of gene expression, remains largely elusive. Here, the material properties of optogenetically induced transcription factor condensates are systematically tuned, and probed for their impact on the activation of target promoters. It is demonstrated that transcription factors in rather liquid condensates correlate with increased gene expression levels, whereas stiffer transcription factor condensates correlate with the opposite effect, reduced activation of gene expression. The broad nature of these findings is demonstrated in mammalian cells and mice, as well as by using different synthetic and natural transcription factors. These effects are observed for both transgenic and cell-endogenous promoters. The findings provide a novel materials-based layer in the control of gene expression, which opens novel opportunities in optogenetic engineering and synthetic biology

    Darstellung von Meissner-Körperchen mit nicht-invasivem in vivo-Imaging

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    The presence of mechanoreceptors in glabrous skin allows humans to discriminate textures by touch. Their quantification as clinical markers by biopsy is an invasive method of diagnosis. We report the localization and quantification of Meissner corpuscles using in vivo, non-invasive optical microscopy techniques. We discovered that regions containing Meissner corpuscles could be easily identified by laser scanning microscopy (LSM) with an enhanced optical reflectance above the corpuscles, caused by a protrusion of the strongly reflecting epidermis into the Stratum corneum with its weak reflectance

    Harnessing enhanced lithium-ion storage in self-assembled organic nanowires for batteries and metal-ion supercapacitors

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    Organic materials have emerged as highly efficient electrodes for electrochemical energy storage, offering sustainable solutions independent from non-renewable resources. In this study, we showcase that mesoscale engineering can dramatically transform the electrochemical features of a molecular organic carboxylic anode. Through a sustainable, energy-efficient and environmentally benign self-assembly strategy, we developed a network of organic nanowires formed during water evaporation directly on the copper current collector, circumventing the need for harmful solvents, typically employed in such processes. The organic nanowire anode delivers high capacity and rate, reaching 1888 mA h g−1 at 0.1 A g−1 and maintaining 508 mA h g−1 at a specific current of 10 A g−1. Moreover, it exhibits superior thermal management during lithiation in comparison to graphite and other organic anodes. Comprehensive electrochemical evaluations and theoretical calculations reveal rapid charge transport mechanisms, with lithium diffusivity rates reaching 5 × 10−9 cm2 s−1, facilitating efficient and rapid interactions with 24 lithium atoms per molecule. Integrated as the negative electrode in a lithium-ion capacitor, paired with a commercially available porous carbon, the cell delivers a specific energy of 156 W h kg−1 at a specific power of 0.34 kW kg−1 and 60.2 W h kg−1 at 19.4 kW kg−1, establishing a benchmark among state-of-the-art systems in the field. These results underscore the critical role of supramolecular organization for optimizing the performance of organic electrode materials for practical and sustainable energy storage technologies

    Self-assembly of hybrid 3D cultures by integrating living and synthetic cells

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    Self-assembly, a fundamental property of living matter, drives the interconnected cellular organization of tissues. Synthetic cell models have been developed as bionic materials to mimic inherent cellular features such as self-assembly. Here, we leverage co-assembly of synthetic and natural cells to create hybrid living 3D cancer cultures. We screened synthetic cell models, including giant unilamellar vesicles, coacervates, microdroplet emulsions, proteinosomes, and colloidosomes, for their ability to form hybrid tumoroids. Our results identify the balance of inter- and extracellular adhesion and synthetic cell surface tension as key material properties driving successful co-assembly of hybrids. We further demonstrate that these synthetic cells can establish artificial tumor immune microenvironments (ART-TIMEs), mimicking immunogenic signals within tumoroids. Using the ART-TIME approach, we identify co-signaling mechanisms between PD-1 and CD2 as a driver in immune evasion of pancreatic ductal adenocarcinoma. Our findings demonstrate the 3D bottom-up self-assembly of hybrid cancer microenvironments to replace immune components with defined bionic materials, pushing the boundaries to functionally integrating living and non-living matter

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    INMdok (Leibniz Institute for New Materials)
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