INMdok (Leibniz Institute for New Materials)
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Photodeagradable hydrogels for tissue gluing
Get PDFHydrogel biomaterials for wound care dressing and tissue gluing need to adhere to tissue and on-demand disappear. Advanced tissue adhesives also envision the encapsulation of therapeutic drugs or cells to promote the healing process. The design of hydrogels with all these functionalities is challenging. In this PhD, hydrogels that fulfil several of the previous properties for wound dressing at reasonable chemical complexity is presented. These hydrogels can be formed in situ and encapsulate cells, they can adhere to tissue and detach after use by light exposure at cytocompatible doses. The developed photodegradable hydrogels are based on 4-star PEG end-catechol precursors for crosslinking, and intercalate photocleavable o-nitrobenzyl groups in their structure. These gels can form at mild oxidative conditions and encapsulate cells or microparticles. UV-vis light exposure (λ= 365 or 405 nm) photocleavables the nitrobenzyl moiety and promotes degradation. This can occur at cytocompatible doses, and enables on-demand detachment from tissue and release of the encapsulated materials or cells. These biomaterials are interesting for the development of advanced tissue adhesives and cell therapies, by expanding the range of functionality of existing choices.Die entwickelten photodegradierbaren Hydrogele basieren auf 4-Stern-PEG, das in dieser Arbeit chemisch mit endständigen Catecholgruppen und photospaltbaren o-Nitrobenzylgruppen modifiziert wurde. Die Vernetzung erfolgt über die Catecholgruppen unter oxidativen Bedingungen in HEPES-Puffer mit 9-18 mM Natriumperiodat als Oxidationsmittel. Diese Bedingungen sind mild genug, um lebende Zellen oder Mikropartikeln in das Material einzubetten. Bei Belichtung mit UV (λ 365 nm) oder sichtbarem Licht (λ 405 nm) in zytokompatiblen Lichtdosen fördert die photospaltbare Nitrobenzyleinheit den Hydrogelabbau, was die on-demand Freisetzung von Zellen und das Ablösen vom Gewebe ermöglicht. Diese Biomaterialien sind interessant für die Entwicklung fortschrittlicher Gewebeklebstoffe und Zelltherapien, und erweitern den Funktionsumfang gegenüber bisherigen Auswahlmöglichkeiten
Analysis of sub-10 nm precipitates extracted from microalloyed steels
Get PDFMicroalloyed steels contain small quantities (≤ 0.5 wt%) of the microalloying elements Ti, Nb, V. Judicious combination of TMCP parameters and microalloyed steel composition leads to formation of desirable nm-sized carbide, nitride, carbonitride inclusions which improve steel mechanical properties. TMCP optimisation relies on understanding the interrelation between TMCP parameters and precipitate properties. A characterisation routine was developed in the group to provide statistically meaningful data on precipitates size distribution and chemical composition.[1] Precipitates with diameters below 10nm could not be investigated with the existing routine. Such precipitates are of interest because they play a key role in precipitation hardening. This thesis extends the existing characterisation routine to sub-10nm precipitates extracted from microalloyed steels. Electrolytic extraction was investigated as alternative extraction process to reduce undesired particle loss during chemical extraction. The suitability of various electrolytes to provide a stable colloidal suspension for colloidal analysis was assessed. Chemically extracted precipitates underwent differential centrifugation to isolate sub-10nm precipitates and enable their size and chemical composition characterisation. Improvements in precipitate analysis were achieved by implementation of speed-ramp analytical ultracentrifugation and precipitate number density determination.Mikrolegierte Stähle enthalten geringe Mengen (≤ 0.5 wt%) der Mikrolegierungselemente Ti, Nb, V. Eine geschickte Kombination aus TMCP-Parametern und Stahlzusammensetzung führt zur Bildung nm-großer Karbid-, Nitrid-, Karbonitrideinschlüsse, die mechanische Eigenschaften verbessern. TMCP-Optimierung beruht auf dem Verständnis des Zusammenhangs zwischen TMCP-Parametern und Ausscheidungseigenschaften. Eine vorhandene Charakterisierungsroutine liefert statistisch aussagekräftige Daten über die Größenverteilung und die chemische Zusammensetzung der Ausscheidungen.[ 1] Ausscheidungen mit Durchmessern unter 10nm konnten mit der bestehenden Methode nicht untersucht werden. Solche Ausscheidungen sind von Interesse, da sie eine Schlüsselrolle bei der Ausscheidungshärtung spielen. Diese Arbeit erweitert die bestehende Charakterisierungsroutine auf extrahierte Ausscheidungen kleiner 10 nm. Elektrolytische Extraktion wurde als alternatives Extraktionsverfahren erprobt, um unerwünschten Partikelverlust zu reduzieren. Die Eignung von Elektrolyten zur Bereitstellung einer stabilen kolloidalen Suspension zur Analyse mit kolloidalen Messmethoden wurde bewertet. Fraktionierung chemisch extrahierter Ausscheidungen mittels Differentialzentrifugation ermöglichte die Charakterisierung von Ausscheidungen kleiner 10 nm. Ausscheidungscharakterisierungsverbesserungen wurden durch Einführung der analytischen Ultrazentrifugation mit Geschwindigkeitsrampe und der Bestimmung der Ausscheidungsdichte erzielt
Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor
Get PDFLiposomes have been studied for decades as nanoparticulate drug delivery systems for cytostatics, and more recently, for antibiotics. Such nanoantibiotics show improved antibacterial efficacy compared to the free drug and can be effective despite bacterial recalcitrance. In this work, we present a loading method of bacteriomimetic liposomes for a novel, hydrophobic compound (HIPS5031) inhibiting energy-coupling factor transporters (ECF transporters), an underexplored antimicrobial target. The liposomes were composed of DOPG (18:1 (Δ9-cis) phosphatidylglycerol) and CL (cardiolipin), resembling the cell membrane of Gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and enriched with cholesterol (Chol). The size and polydispersity of the DOPG/CL/± Chol liposomes remained stable over 8 weeks when stored at 4 °C. Loading of the ECF transporter inhibitor was achieved by thin film hydration and led to a high encapsulation efficiency of 33.19% ± 9.5% into the DOPG/CL/Chol liposomes compared to the phosphatidylcholine liposomes (DMPC/DPPC). Bacterial growth inhibition assays on the model organism Bacillus subtilis revealed liposomal HIPS5031 as superior to the free drug, showing a 3.5-fold reduction in CFU/mL at a concentration of 9.64 µM. Liposomal HIPS5031 was also shown to reduce B. subtilis biofilm. Our findings present an explorative basis for bacteriomimetic liposomes as a strategy against drug-resistant pathogens by surpassing the drug-formulation barriers of innovative, yet unfavorably hydrophobic, antibiotics
An Outer Membrane Vesicle-Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability
Get PDFWhen searching for new antibiotics against Gram-negative bacterial infections, a better understanding of the permeability across the cell envelope and tools to discriminate high from low bacterial bioavailability compounds are urgently needed. Inspired by the phospholipid vesicle-based permeation assay (PVPA), which is designed to predict non-facilitated permeation across phospholipid membranes, outer membrane vesicles (OMVs) of Escherichia coli either enriched or deficient of porins are employed to coat filter supports for predicting drug uptake across the complex cell envelope. OMVs and the obtained in vitro model are structurally and functionally characterized using cryo-TEM, SEM, CLSM, SAXS, and light scattering techniques. In vitro permeability, obtained from the membrane model for a set of nine antibiotics, correlates with reported in bacterio accumulation data and allows to discriminate high from low accumulating antibiotics. In contrast, the correlation of the same data set generated by liposome-based comparator membranes is poor. This better correlation of the OMV-derived membranes points to the importance of hydrophilic membrane components, such as lipopolysaccharides and porins, since those features are lacking in liposomal comparator membranes. This approach can offer in the future a high throughput screening tool with high predictive capacity or can help to identify compound- and bacteria-specific passive uptake pathways
Squish this: force input on soft surfaces for visual targeting tasks
Get PDFToday's typical input device is flat, rigid and made of glass. However, advances in sensing technology and interaction design suggest thinking about input on other surface, including soft materials. While touching rigid and soft materials might feel similar, they clearly feel different when pressure is applied to them. Yet, to date, studies only investigated force input on rigid surfaces. We present a first systematic evaluation of the effects of compliance on force input. Results of a visual targeting task for three levels of softness indicate that high force levels appear more demanding for soft surfaces, but that performance is otherwise similar. Performance remained very high (∼ 5% for 20 force levels) regardless of the compliance, suggesting force input was underestimated so far. We infer implications for the design of force input on soft surfaces and conclude that interaction models used on rigid surfaces might be used on soft surfaces
A Design Strategy for Mushroom-Shaped Microfibrils with Optimized Dry Adhesion: Experiments and Finite Element Analyses
Get PDFEnhanced dry adhesion of micropatterned polymeric surfaces has been frequently demonstrated. Among the design parameters, the cap geometry plays an important role to improve their performance. In this work, we combined experiments on single polyurethane mushroom-shaped fibrils (with stalk diameter 80 µm and height 125 µm) against flat glass, with numerical simulations implementing a cohesive zone. We found that the geometry of the mushroom cap strongly affects the interfacial crack behavior and the pull-off stress. The experimental and numerical results suggest that optimal adhesion was accompanied by the appearance of both edge and interior interfacial cracks during separation. Finite elemental analyses revealed the evolution of the interfacial stress distributions as a function of the cap thickness and confirmed the distinct detachment mechanisms. Furthermore, the effect of the stalk diameter and the Young's modulus on the adhesive force was established, resulting in an optimal design for mushroom-shaped fibrils
Bioactive constituents of Verbena officinalis regulate killing efficiency of primary human natural killer cells by accelerating killing processes
Get PDFBackground Natural killer (NK) cells play a key role in eliminating tumorigenic and pathogen-infected cells. Verbena officinalis (V. officinalis) has been used as a medical plant in traditional and modern medicine, exhibiting anti-tumor and anti-inflammation activity.Purpose The impact of bioactive constituents of V. officinalis on immune responses still remains largely elusive. In this work we investigated the potential targets of V. officinalis and focused on killing efficiency and related functions of NK cells regulated by bioactive constituents of V. officinalis.Study design/methods We used primary human NK cells from peripheral blood mononuclear cells. Potential regulatory roles of selected compounds were analyzed by network pharmacology approaches. Killing efficiency was determined with real-time killing assay and live-cell imaging in 3D. Proliferation was examined by CFSE staining. Expression of cytotoxic proteins was analyzed using flow cytometry. Lytic granule release was quantified by CD107a degranulation assay. Contact time required for killing and determination of serial killers were analyzed using live cell imaging results. Results: Using network pharmacology approaches, we analyzed potential regulatory roles of five compounds (Acteoside, Apigenin, Kaempferol, Verbenalin and Hastatoside) from V. officinalis on immune cell functions and revealed NK cells as a major target. The effect of these compounds on NK killing efficiency was examined with real-time killing assay, and Verbenalin enhanced NK killing efficiency significantly. Further investigation showed that Verbenalin did not affect proliferation, expression of cytotoxic proteins, or lytic granule degranulation, but rather reduced contact time required for killing therefore enhancing total killing events per NK cell, suggestively via inhibition of inhibitory receptors as determined by docking assay.Conclusions Our findings reveal the underlying mechanisms how V. officinalis regulates functions of immune cells, especially NK cells, suggesting Verbenalin from V. officinalis as a promising therapeutic reagent to fight cancer and infection.Competing Interest StatementThe authors have declared no competing interest
Preventing Catastrophic Failure of Microfibrillar Adhesives in Compliant Systems Based on Statistical Analysis of Adhesive Strength
Get PDFAdhesives based on fibrillar surface microstructures have shown great potential for handling applications requiring strong, reversible, and switchable adhesion. Recently, the importance of the statistical distribution of adhesive strength of individual fibrils in controlling the overall performance was revealed. Strength variations physically correspond to different interfacial defect sizes, which, among other factors, are related to surface roughness. For analysis of the strength distribution, Weibull’s statistical theory of fracture was introduced. In this study, the importance of the statistical properties in controlling the stability of attachment is explored. Considering the compliance of the loading system, we develop a stability criterion based on the Weibull statistical parameters. It is shown that when the distribution in fibril adhesive strength is narrow, the global strength is higher but unstable detachment is more likely. Experimental variation of the loading system compliance for a specimen of differing statistical properties shows a transition to unstable detachment at low system stiffness, in good agreement with the theoretical stability map. This map serves to inform the design of gripper compliance, when coupled with statistical analysis of strength on the target surface of interest. Such a treatment could prevent catastrophic failure by spontaneous detachment of an object from an adhesive gripper
Three-Dimensional Cobalt Hydroxide Hollow Cube/Vertical Nanosheets with High Desalination Capacity and Long-Term Performance Stability
Get PDFFaradaic electrode materials have significantly improved the performance of membrane capacitive deionization, which offers an opportunity to produce freshwater from seawater or brackish water in an energy-efficient way. However, Faradaic materials hold the drawbacks of slow desalination rate due to the intrinsic low ion diffusion kinetics and inferior stability arising from the volume expansion during ion intercalation, impeding the engineering application of capacitive deionization. Herein, a pseudocapacitive material with hollow architecture was prepared via template-etching method, namely, cuboid cobalt hydroxide, with fast desalination rate (3.3 mg (NaCl)·g-1 (h-Co(OH)2)·min-1 at 100 mA·g-1) and outstanding stability (90% capacity retention after 100 cycles). The hollow structure enables swift ion transport inside the material and keeps the electrode intact by alleviating the stress induced from volume expansion during the ion capture process, which is corroborated well by in situ electrochemical dilatometry and finite element simulation. Additionally, benefiting from the elimination of unreacted bulk material and vertical cobalt hydroxide nanosheets on the exterior surface, the synthesized material provides a high desalination capacity ( mg (NaCl)·g-1 (h-Co(OH)2) at 30 mA·g-1). This work provides a new strategy, constructing microscale hollow faradic configuration, to further boost the desalination performance of Faradaic materials
Targeting the Microtubule-Network Rescues CTL Killing Efficiency in Dense 3D Matrices
Get PDFEfficacy of cytotoxic T lymphocyte (CTL)-based immunotherapy is still unsatisfactory against solid tumors, which are frequently characterized by condensed extracellular matrix. Here, using a unique 3D killing assay, we identify that the killing efficiency of primary human CTLs is substantially impaired in dense collagen matrices. Although the expression of cytotoxic proteins in CTLs remained intact in dense collagen, CTL motility was largely compromised. Using light-sheet microscopy, we found that persistence and velocity of CTL migration was influenced by the stiffness and porosity of the 3D matrix. Notably, 3D CTL velocity was strongly correlated with their nuclear deformability, which was enhanced by disruption of the microtubule network especially in dense matrices. Concomitantly, CTL migration, search efficiency, and killing efficiency in dense collagen were significantly increased in microtubule-perturbed CTLs. In addition, the chemotherapeutically used microtubule inhibitor vinblastine drastically enhanced CTL killing efficiency in dense collagen. Together, our findings suggest targeting the microtubule network as a promising strategy to enhance efficacy of CTL-based immunotherapy against solid tumors, especially stiff solid tumors