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Compartmentalized Jet Polymerization as a High-Resolution Process to Continuously Produce Anisometric Microgel Rods with Adjustable Size and Stiffness

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, Laura

In 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

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Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension

2019, Licht, Christopher, Rose, Jonas C., Anarkoli, Abdolrahman Omidinia, Blondel, Delphine, Roccio, Marta, Haraszti, Tamás, Gehlen, David B., Hubbell, Jeffrey A., Lutolf, Matthias P., De Laporte, Laura

An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanical and biochemical properties were optimized. A recombinant fibronectin fragment (FNIII9*-10/12-14) was coupled to the PEG backbone during gelation to provide cell adhesive and growth factor binding domains in close vicinity. Compared to full-length fibronectin, FNIII9*-10/12-14 supports nerve growth at similar concentrations. In a 3D environment, only the ultrasoft 1 w/v% PEG hydrogels with a storage modulus of ∼10 Pa promoted neuronal growth. This gel was used to establish the first fully synthetic, injectable Anisogel by the addition of magnetically aligned microelements, such as rod-shaped microgels or short fibers. The Anisogel led to linear neurite extension and represents a large step in the direction of clinical translation with the opportunity to treat acute spinal cord injuries.