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- 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
- ItemGranular Cellulose Nanofibril Hydrogel Scaffolds for 3D Cell Cultivation(Weinheim : Wiley-VCH, 2020) Gehlen, David B.; Jürgens, Niklas; Omidinia-Anarkoli, Abdolrahman; Haraszti, Tamás; George, Julian; Walther, Andreas; Ye, Hua; De Laporte, LauraThe replacement of diseased and damaged organs remains an challenge in modern medicine. However, through the use of tissue engineering techniques, it may soon be possible to (re)generate tissues and organs using artificial scaffolds. For example, hydrogel networks made from hydrophilic precursor solutions can replicate many properties found in the natural extracellular matrix (ECM) but often lack the dynamic nature of the ECM, as many covalently crosslinked hydrogels possess elastic and static networks with nanoscale pores hindering cell migration without being degradable. To overcome this, macroporous colloidal hydrogels can be prepared to facilitate cell infiltration. Here, an easy method is presented to fabricate granular cellulose nanofibril hydrogel (CNF) scaffolds as porous networks for 3D cell cultivation. CNF is an abundant natural and highly biocompatible material that supports cell adhesion. Granular CNF scaffolds are generated by pre-crosslinking CNF using calcium and subsequently pressing the gel through micrometer-sized nylon meshes. The granular solution is mixed with fibroblasts and crosslinked with cell culture medium. The obtained granular CNF scaffold is significantly softer and enables well-distributed fibroblast growth. This cost-effective material combined with this efficient and facile fabrication technique allows for 3D cell cultivation in an upscalable manner. © 2020 The Authors. Published by Wiley-VCH GmbH
- ItemCompartmentalized Jet Polymerization as a High-Resolution Process to Continuously Produce Anisometric Microgel Rods with Adjustable Size and Stiffness(Weinheim : Wiley-VCH, 2019) Krüger, Andreas J.D.; Bakirman, Onur; Guerzoni, Luis P.B.; Jans, Alexander; Gehlen, David B.; Rommel, Dirk; Haraszti, Tamás; Kuehne, Alexander J.C.; De Laporte, LauraIn the past decade, anisometric rod-shaped microgels have attracted growing interest in the materials-design and tissue-engineering communities. Rod-shaped microgels exhibit outstanding potential as versatile building blocks for 3D hydrogels, where they introduce macroscopic anisometry, porosity, or functionality for structural guidance in biomaterials. Various fabrication methods have been established to produce such shape-controlled elements. However, continuous high-throughput production of rod-shaped microgels with simultaneous control over stiffness, size, and aspect ratio still presents a major challenge. A novel microfluidic setup is presented for the continuous production of rod-shaped microgels from microfluidic plug flow and jets. This system overcomes the current limitations of established production methods for rod-shaped microgels. Here, an on-chip gelation setup enables fabrication of soft microgel rods with high aspect ratios, tunable stiffness, and diameters significantly smaller than the channel diameter. This is realized by exposing jets of a microgel precursor to a high intensity light source, operated at specific pulse sequences and frequencies to induce ultra-fast photopolymerization, while a change in flow rates or pulse duration enables variation of the aspect ratio. The microgels can assemble into 3D structures and function as support for cell culture and tissue engineering. © 2019 DWI – Leibniz Institute for Interactive Materials. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim