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Guiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays

2021, Riegert, Janine, Töpel, Alexander, Schieren, Jana, Coryn, Renee, Dibenedetto, Stella, Braunmiller, Dominik, Zajt, Kamil, Schalla, Carmen, Rütten, Stephan, Zenke, Martin, Pich, Andrij, Sechi, Antonio, Blank, Kerstin G.

Biomaterial-driven modulation of cell adhesion and migration is a challenging aspect of tissue engineering. Here, we investigated the impact of surface-bound microgel arrays with variable geometry and adjustable cross-linking properties on cell adhesion and migration. We show that cell migration is inversely correlated with microgel array spacing, whereas directionality increases as array spacing increases. Focal adhesion dynamics is also modulated by microgel topography resulting in less dynamic focal adhesions on surface-bound microgels. Microgels also modulate the motility and adhesion of Sertoli cells used as a model for cell migration and adhesion. Both focal adhesion dynamics and speed are reduced on microgels. Interestingly, Gas2L1, a component of the cytoskeleton that mediates the interaction between microtubules and microfilaments, is dispensable for the regulation of cell adhesion and migration on microgels. Finally, increasing microgel cross-linking causes a clear reduction of focal adhesion turnover in Sertoli cells. These findings not only show that spacing and rigidity of surface-grafted microgels arrays can be effectively used to modulate cell adhesion and motility of diverse cellular systems, but they also form the basis for future developments in the fields of medicine and tissue engineering.

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Templating the morphology of soft microgel assemblies using a nanolithographic 3D-printed membrane

2021, Linkhorst, John, Lölsberg, Jonas, Thill, Sebastian, Lohaus, Johannes, Lüken, Arne, Naegele, Gerhard, Wessling, Matthias

Filter cake formation is the predominant phenomenon limiting the filtration performance of membrane separation processes. However, the filter cake’s behavior at the particle scale, which determines its overall cake behavior, has only recently come into the focus of scientists, leaving open questions about its formation and filtration behavior. The present study contributes to the fundamental understanding of soft filter cakes by analyzing the influence of the porous membrane’s morphology on crystal formation and the compaction behavior of soft filter cakes under filtration conditions. Microfluidic chips with nanolithographic imprinted filter templates were used to trigger the formation of crystalline colloidal filter cakes formed by soft microgels. The soft filter cakes were observed via confocal laser scanning microscopy (CLSM) under dead-end filtration conditions. Colloidal crystal formation in the cake, as well as their compaction behavior, were analyzed by optical visualization and pressure data. For the first time, we show that exposing the soft cake to a crystalline filter template promotes the formation of colloidal crystallites and that soft cakes experience gradient compression during filtration.

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Safe and efficient 2D molybdenum disulfide platform for cooperative imaging-guided photothermal-selective chemotherapy: A preclinical study

2021, Li, Xin, Kong, Lingdan, Hu, Wei, Zhang, Changchang, Pich, Andrij, Shi, Xiangyang, Wang, Xipeng, Xing, Lingxi

Introduction: The striking imbalance between the ever-increasing amount of nanomedicines and low clinical translation of products has become the focus of intense debate. For clinical translation, the critical issue is to select the appropriate agents and combination regimen for targeted diseases, not to prepare increasingly complex nanoplatforms. Objectives: A safe and efficient platform, α-tocopheryl succinate (α-TOS) married 2D molybdenum disulfide, was devised by a facile method and applied for cooperative imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Methods: A novel platform of PEGylated α-TOS and folic acid (FA) conjugated 2D MoS2 nanoflakes was fabricated for the cooperative multimode computed tomography (CT)/photoacoustic (PA)/thermal imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Results: The photothermal efficiency (65.3%) of the platform under safe near-infrared irradiation is much higher than that of other photothermal materials reported elsewhere. Moreover, the covalently linked α-TOS renders platform with selective chemotherapy for cancer cells. Remarkably, with these excellent properties, the platform can be used to completely eliminate the solid tumor by safe photothermal therapy, and then kill the residual cancer cells by selective chemotherapy to prevent tumor recurrence. More significantly, barely side effects occur in the whole treatment process. The excellent efficacy and safety benefits in vivo lead to the prominent survival rate of 100% over 91 days. Conclusion: The safe and efficient platform might be a candidate of clinical nanomedicines for multimode theranostics. This study demonstrates an innovative thought in precise nanomedicine regarding the design of next generation of cancer theranostic protocol for potential clinical practice.

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Particle movements provoke avalanche-like compaction in soft colloid filter cakes

2021, Lüken, Arne, Stüwe, Lucas, Lohaus, Johannes, Linkhorst, John, Wessling, Matthias

During soft matter filtration, colloids accumulate in a compressible porous cake layer on top of the membrane surface. The void size between the colloids predominantly defines the cake-specific permeation resistance and the corresponding filtration efficiency. While higher fluxes are beneficial for the process efficiency, they compress the cake and increase permeation resistance. However, it is not fully understood how soft particles behave during cake formation and how their compression influences the overall cake properties. This study visualizes the formation and compression process of soft filter cakes in microfluidic model systems. During cake formation, we analyze single-particle movements inside the filter cake voids and how they interact with the whole filter cake morphology. During cake compression, we visualize reversible and irreversible compression and distinguish the two phenomena. Finally, we confirm the compression phenomena by modeling the soft particle filter cake using a CFD-DEM approach. The results underline the importance of considering the compression history when describing the filter cake morphology and its related properties. Thus, this study links single colloid movements and filter cake compression to the overall cake behavior and narrows the gap between single colloid events and the filtration process.

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Ultra-strong bio-glue from genetically engineered polypeptides

2021, Ma, Chao, Sun, Jing, Li, Bo, Feng, Yang, Sun, Yao, Xiang, Li, Wu, Baiheng, Xiao, Lingling, Liu, Baimei, Petrovskii, Vladislav S., Zhang, Jinrui, Wang, Zili, Li, Hongyan, Zhang, Lei, Li, Jingjing, Wang, Fan, Gӧstl, Robert, Potemkin, Igor I., Chen, Dong, Zeng, Hongbo, Zhang, Hongjie, Liu, Kai, Herrmann, Andreas

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue’s robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.