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- ItemBiocompatible Micron-Scale Silk Fibers Fabricated by Microfluidic Wet Spinning(Weinheim : Wiley-VCH, 2021) Lüken, Arne; Geiger, Matthias; Steinbeck, Lea; Joel, Anna-Christin; Lampert, Angelika; Linkhorst, John; Wessling, MatthiasFor successful material deployment in tissue engineering, the material itself, its mechanical properties, and the microscopic geometry of the product are of particular interest. While silk is a widely applied protein-based tissue engineering material with strong mechanical properties, the size and shape of artificially spun silk fibers are limited by existing processes. This study adjusts a microfluidic spinneret to manufacture micron-sized wet-spun fibers with three different materials enabling diverse geometries for tissue engineering applications. The spinneret is direct laser written (DLW) inside a microfluidic polydimethylsiloxane (PDMS) chip using two-photon lithography, applying a novel surface treatment that enables a tight print-channel sealing. Alginate, polyacrylonitrile, and silk fibers with diameters down to 1 µm are spun, while the spinneret geometry controls the shape of the silk fiber, and the spinning process tailors the mechanical property. Cell-cultivation experiments affirm bio-compatibility and showcase an interplay between the cell-sized fibers and cells. The presented spinning process pushes the boundaries of fiber fabrication toward smaller diameters and more complex shapes with increased surface-to-volume ratio and will substantially contribute to future tailored tissue engineering materials for healthcare applications. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
- ItemControlling Structure with Injectable Biomaterials to Better Mimic Tissue Heterogeneity and Anisotropy(Weinheim : Wiley-VCH, 2021) Babu, Susan; Albertino, Filippo; Omidinia-Anarkoli, Abdolrahman; De Laporte, LauraTissue regeneration of sensitive tissues calls for injectable scaffolds, which are minimally invasive and offer minimal damage to the native tissues. However, most of these systems are inherently isotropic and do not mimic the complex hierarchically ordered nature of the native extracellular matrices. This review focuses on the different approaches developed in the past decade to bring in some form of anisotropy to the conventional injectable tissue regenerative matrices. These approaches include introduction of macroporosity, in vivo pattering to present biomolecules in a spatially and temporally controlled manner, availability of aligned domains by means of self-assembly or oriented injectable components, and in vivo bioprinting to obtain structures with features of high resolution that resembles native tissues. Toward the end of the review, different techniques to produce building blocks for the fabrication of heterogeneous injectable scaffolds are discussed. The advantages and shortcomings of each approach are discussed in detail with ideas to improve the functionality and versatility of the building blocks. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
- ItemGuiding cell adhesion and motility by modulating cross-linking and topographic properties of microgel arrays(San Francisco, California, US : PLOS, 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.
- ItemAnisometric Microstructures to Determine Minimal Critical Physical Cues Required for Neurite Alignment(Weinheim : Wiley-VCH, 2021) Vedaraman, Sitara; Perez-Tirado, Amaury; Haraszti, Tamas; Gerardo-Nava, Jose; Nishiguchi, Akihiro; De Laporte, LauraIn nerve regeneration, scaffolds play an important role in providing an artificial extracellular matrix with architectural, mechanical, and biochemical cues to bridge the site of injury. Directed nerve growth is a crucial aspect of nerve repair, often introduced by engineered scaffolds imparting linear tracks. The influence of physical cues, determined by well-defined architectures, has been mainly studied for implantable scaffolds and is usually limited to continuous guiding features. In this report, the potential of short anisometric microelements in inducing aligned neurite extension, their dimensions, and the role of vertical and horizontal distances between them, is investigated. This provides crucial information to create efficient injectable 3D materials with discontinuous, in situ magnetically oriented microstructures, like the Anisogel. By designing and fabricating periodic, anisometric, discreet guidance cues in a high-throughput 2D in vitro platform using two-photon lithography techniques, the authors are able to decipher the minimal guidance cues required for directed nerve growth along the major axis of the microelements. These features determine whether axons grow unidirectionally or cross paths via the open spaces between the elements, which is vital for the design of injectable Anisogels for enhanced nerve repair. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
- ItemA New Approach to Harness Probiotics Against Common Bacterial Skin Pathogens: Towards Living Antimicrobials(New York, NY [u.a.] : Springer, 2021) Khalfallah, Ghazi; Gartzen, Rita; Möller, Martin; Heine, Elisabeth; Lütticken, RudolfIn this study, the potential of certain lactic acid bacteria—classified as probiotics and known to be antimicrobially active against pathogens or food-poisoning microorganisms—was evaluated with respect to their activity against bacterial skin pathogens. The aim of the study was to develop a plaster/bandage for the application of inhibitory substances produced by these probiotics when applied to diseased skin. For this purpose, two Streptococcus salivarius strains and one Lactobacillus plantarum were tested for production of antimicrobials (bacteriocin-like substances) active against Gram-positive and Gram-negative pathogens using established methods. A newly designed membrane test ensured that the probiotics produce antimicrobials diffusible through membranes. Target organisms used were Cutibacterium acnes, Staphylococcus aureus, and Pseudomonas aeruginosa. Moreover, the L. plantarum 8P-A3 strain was tested against additional bacteria involved in skin disorders. The Lactobacillales used were active against all potential skin pathogens tested. These probiotics could be enclosed between polymer membranes—one tight, the other permeable for their products, preserved by vacuum drying, and reactivated after at least three months storage. Importantly, the reactivated pads containing the probiotics demonstrated antibacterial activity on agar plates against all pathogens tested. This suggests that the probiotic containing pads may be topically applied for the treatment of skin disorders without the need for a regular antibiotic treatment or as an adjunctive therapy.