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- ItemPhysioSkin: Rapid Fabrication of Skin-Conformal Physiological Interfaces(New York,NY,United States : Association for Computing Machinery, 2020) Nittala, Aditya Shekhar; Khan, Arshad; Kruttwig, Klaus; Kraus, Tobias; Steimle, Jürgen; Bernhaupt, ReginaAdvances in rapid prototyping platforms have made physiological sensing accessible to a wide audience. However, off-the-shelf electrodes commonly used for capturing biosignals are typically thick, non-conformal and do not support customization. We present PhysioSkin, a rapid, do-it-yourself prototyping method for fabricating custom multi-modal physiological sensors, using commercial materials and a commodity desktop inkjet printer. It realizes ultrathin skin-conformal patches (~1μm) and interactive textiles that capture sEMG, EDA and ECG signals. It further supports fabricating devices with custom levels of thickness and stretchability. We present detailed fabrication explorations on multiple substrate materials, functional inks and skin adhesive materials. Informed from the literature, we also provide design recommendations for each of the modalities. Evaluation results show that the sensor patches achieve a high signal-to-noise ratio. Example applications demonstrate the functionality and versatility of our approach for prototyping a next generation of physiological devices that intimately couple with the human body.
- ItemA Rotating Spiral Micromotor for Noninvasive Zygote Transfer(Hoboke, NJ : Wiley, 2020) Schwarz, Lukas; Karnaushenko, Dmitriy D.; Hebenstreit, Franziska; Naumann, Ronald; Schmidt, Oliver G.; Medina-Sánchez, MarianaEmbryo transfer (ET) is a decisive step in the in vitro fertilization process. In most cases, the embryo is transferred to the uterus after several days of in vitro culture. Although studies have identified the beneficial effects of ET on proper embryo development in the earlier stages, this strategy is compromised by the necessity to transfer early embryos (zygotes) back to the fallopian tube instead of the uterus, which requires a more invasive, laparoscopic procedure, termed zygote intrafallopian transfer (ZIFT). Magnetic micromotors offer the possibility to mitigate such surgical interventions, as they have the potential to transport and deliver cellular cargo such as zygotes through the uterus and fallopian tube noninvasively, actuated by an externally applied rotating magnetic field. This study presents the capture, transport, and release of bovine and murine zygotes using two types of magnetic micropropellers, helix and spiral. Although helices represent an established micromotor architecture, spirals surpass them in terms of motion performance and with their ability to reliably capture and secure the cargo during both motion and transfer between different environments. Herein, this is demonstrated with murine oocytes/zygotes as the cargo; this is the first step toward the application of noninvasive, magnetic micromotor‐assisted ZIFT.
- ItemPhotobiomodulation of lymphatic drainage and clearance: Perspective strategy for augmentation of meningeal lymphatic functions(Washington, DC : Optica, 2020) Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Klimova, Maria; Agranovich, Ilana; Terskov, Andrey; Shirokov, Alexander; Vinnik, Valeria; Kuzmina, Anna; Lezhnev, Nikita; Blokhina, Inna; Shnitenkova, Anastassia; Tuchin, Valery; Rafailov, Edik; Kurths, JurgenThere is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases.
- ItemAutofluorescence guided welding of heart tissue by laser pulse bursts at 1550 nm(Washington, DC : Optica, 2020) Litvinova, Karina; Chernysheva, Maria; Stegemann, Berthold; Leyva, FranciscoWound healing and other surgical technologies traditionally solved by suturing and stapling have recently been enhanced by the application of laser tissue welding. The usage of high energy laser radiation to anastomose tissues eliminates a foreign body reaction, reduces scar formation, and allows for the creation of watertight closure. In the current work, we show that an ultrafast pulsed fibre laser beam with 183 µJ·cm−2 energy fluence at 1550 nm provides successful welding of dissected chicken heart walls with the tensile strength of 1.03±0.12 kg·cm−2 equal to that of native tissue. The welding process was monitored employing fluorescence spectroscopy that detects the biochemical composition of tissues. We believe that fluorescence spectroscopy guided laser tissue welding is a promising approach for decreasing wound healing times and the avoiding risks of postoperative complications.
- ItemHow Much Physical Guidance is Needed to Orient Growing Axons in 3D Hydrogels?(Weinheim : Wiley-VCH, 2020) Rose, Jonas C.; Gehlen, David B.; Omidinia-Anarkoli, Abdolrahman; Fölster, Maaike; Haraszti, Tamás; Jaekel, Esther E.; De Laporte, LauraDirecting cells is essential to organize multi-cellular organisms that are built up from subunits executing specific tasks. This guidance requires a precisely controlled symphony of biochemical, mechanical, and structural signals. While many guiding mechanisms focus on 2D structural patterns or 3D biochemical gradients, injectable material platforms that elucidate how cellular processes are triggered by defined 3D physical guiding cues are still lacking but crucial for the repair of soft tissues. Herein, a recently developed anisotropic injectable hybrid hydrogel (Anisogel) contains rod-shaped microgels that orient in situ by a magnetic field and has propelled studying 3D cell guidance. Here, the Anisogel is used to investigate the dependence of axonal guidance on microgel dimensions, aspect ratio, and distance. While large microgels result in high material anisotropy, they significantly reduce neurite outgrowth and thus the guidance efficiency. Narrow and long microgels enable strong axonal guidance with maximal outgrowth including cell sensing over distances of tens of micrometers in 3D. Moreover, nerve cells decide to orient inside the Anisogel within the first three days, followed by strengthening of the alignment, which goes along with oriented fibronectin deposition. These findings demonstrate the potential of the Anisogel to tune structural and mechanical parameters for specific applications. © 2020 The Authors. Published by Wiley-VCH GmbH
- ItemDigitally Fabricated and Naturally Augmented In Vitro Tissues(Weinheim : Wiley-VCH, 2020) Duarte Campos, Daniela F.; De Laporte, LauraHuman in vitro tissues are extracorporeal 3D cultures of human cells embedded in biomaterials, commonly hydrogels, which recapitulate the heterogeneous, multiscale, and architectural environment of the human body. Contemporary strategies used in 3D tissue and organ engineering integrate the use of automated digital manufacturing methods, such as 3D printing, bioprinting, and biofabrication. Human tissues and organs, and their intra- and interphysiological interplay, are particularly intricate. For this reason, attentiveness is rising to intersect materials science, medicine, and biology with arts and informatics. This report presents advances in computational modeling of bioink polymerization and its compatibility with bioprinting, the use of digital design and fabrication in the development of fluidic culture devices, and the employment of generative algorithms for modeling the natural and biological augmentation of in vitro tissues. As a future direction, the use of serially linked in vitro tissues as human body-mimicking systems and their application in drug pharmacokinetics and metabolism, disease modeling, and diagnostics are discussed. © 2020 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
- ItemSupramolecular organization as a factor of ribonuclease cytotoxicity(Moscow : Park Media, 2020) Dudkina, Elena V.; Ulyanova, Vera V.; Ilinskaya, Olga N.One of the approaches used to eliminate tumor cells is directed destruction/modification of their RNA molecules. In this regard, ribonucleases (RNases) possess a therapeutic potential that remains largely unexplored. It is believed that the biological effects of secreted RNases, namely their antitumor and antiviral properties, derive from their catalytic activity. However, a number of recent studies have challenged the notion that the activity of RNases in the manifestation of selective cytotoxicity towards cancer cells is exclusively an enzymatic one. In this review, we have analyzed available data on the cytotoxic effects of secreted RNases, which are not associated with their catalytic activity, and we have provided evidence that the most important factor in the selective apoptosis-inducing action of RNases is the structural organization of these enzymes, which determines how they interact with cell components. The new idea on the preponderant role of non-catalytic interactions between RNases and cancer cells in the manifestation of selective cytotoxicity will contribute to the development of antitumor RNase-based drugs.
- ItemLabel‐Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells(Hoboken, NJ : Wiley, 2020) Dumitru, Andra C.; Mohammed, Danahe; Maja, Mauriane; Yang, Jinsung; Verstraeten, Sandrine; del Campo, Aranzazu; Mingeot-Leclercq, Marie-Paule; Tyteca, Donatienne; Alsteens, DavidTumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label‐free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM‐associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease.
- ItemDesign, implementation, evaluation and application of a 32-channel radio frequency signal generator for thermal magnetic resonance based anti-cancer treatment(Basel : MDPI AG, 2020) Han, Haopeng; Eigentler, Thomas Wilhelm; Wang, Shuailin; Kretov, Egor; Winter, Lukas; Hoffmann, Werner; Grass, Eckhard; Niendorf, ThoralfThermal Magnetic Resonance (ThermalMR) leverages radio frequency (RF)-induced heating to examine the role of temperature in biological systems and disease. To advance RF heating with multi-channel RF antenna arrays and overcome the shortcomings of current RF signal sources, this work reports on a 32-channel modular signal generator (SGPLL). The SGPLL was designed around phase-locked loop (PLL) chips and a field-programmable gate array chip. To examine the system properties, switching/settling times, accuracy of RF power level and phase shifting were characterized. Electric field manipulation was successfully demonstrated in deionized water. RF heating was conducted in a phantom setup using self-grounded bow-tie RF antennae driven by the SGPLL. Commercial signal generators limited to a lower number of RF channels were used for comparison. RF heating was evaluated with numerical temperature simulations and experimentally validated with MR thermometry. Numerical temperature simulations and heating experiments controlled by the SGPLL revealed the same RF interference patterns. Upon RF heating similar temperature changes across the phantom were observed for the SGPLL and for the commercial devices. To conclude, this work presents the first 32-channel modular signal source for RF heating. The large number of coherent RF channels, wide frequency range and accurate phase shift provided by the SGPLL form a technological basis for ThermalMR controlled hyperthermia anti-cancer treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemAffinity for the Interface Underpins Potency of Antibodies Operating In Membrane Environments(Maryland Heights, MO : Cell Press, 2020) Rujas, Edurne; Insausti, Sara; Leaman, Daniel P.; Carravilla, Pablo; González-Resines, Saul; Monceaux, Valérie; Sánchez-Eugenia, Rubén; Garcıá-Porras, Miguel; Iloro, Ibon; Zhang, Lei; Elortza, Félix; Julien, Jean-Philippe; Saéz-Cirión, Asier; Zwick, Michael B.; Eggeling, Christian; Ojida, Akio; Domene, Carmen; Caaveiro, Jose M.M.; Nieva, José L.The contribution of membrane interfacial interactions to recognition of membrane-embedded antigens by antibodies is currently unclear. This report demonstrates the optimization of this type of antibodies via chemical modification of regions near the membrane but not directly involved in the recognition of the epitope. Using the HIV-1 antibody 10E8 as a model, linear and polycyclic synthetic aromatic compounds are introduced at selected sites. Molecular dynamics simulations predict the favorable interactions of these synthetic compounds with the viral lipid membrane, where the epitope of the HIV-1 glycoprotein Env is located. Chemical modification of 10E8 with aromatic acetamides facilitates the productive and specific recognition of the native antigen, partially buried in the crowded environment of the viral membrane, resulting in a dramatic increase of its capacity to block viral infection. These observations support the harnessing of interfacial affinity through site-selective chemical modification to optimize the function of antibodies that target membrane-proximal epitopes. © 2020 The Author(s)Rujas et al. describe the site-selective chemical modification of antibodies to improve the molecular recognition of epitopes at membrane surfaces. The modification using aromatic compounds dramatically enhanced the virus neutralization potency and native antigen binding efficiency of HIV-1 antibodies directed against the membrane-embedded MPER epitope. © 2020 The Author(s)