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- ItemCellular responses to beating hydrogels to investigate mechanotransduction([London] : Nature Publishing Group UK, 2019) Chandorkar, Yashoda; Castro Nava, Arturo; Schweizerhof, Sjören; Van Dongen, Marcel; Haraszti, Tamás; Köhler, Jens; Zhang, Hang; Windoffer, Reinhard; Mourran, Ahmed; Möller, Martin; De Laporte, LauraCells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. While many cell fate processes are dictated by these forces, which are highly synchronized in space and time, abnormal force transduction is implicated in the progression of many diseases (muscular dystrophy, cancer). However, material platforms that enable transient, cyclic forces in vitro to recreate an in vivo-like scenario remain a challenge. Here, we report a hydrogel system that rapidly beats (actuates) with spatio-temporal control using a near infra-red light trigger. Small, user-defined mechanical forces (~nN) are exerted on cells growing on the hydrogel surface at frequencies up to 10 Hz, revealing insights into the effect of actuation on cell migration and the kinetics of reversible nuclear translocation of the mechanosensor protein myocardin related transcription factor A, depending on the actuation amplitude, duration and frequency.
- 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
- ItemBiofunctionalized aligned microgels provide 3D cell guidance to mimic complex tissue matrices(Amsterdam [u.a.] : Elsevier, 2018) Rose, Jonas C.; Gehlen, David B.; Haraszti, Tamás; Köhler, Jens; Licht, Christopher J.; De Laporte, LauraNatural healing is based on highly orchestrated processes, in which the extracellular matrix plays a key role. To resemble the native cell environment, we introduce an artificial extracellular matrix (aECM) with the capability to template hierarchical and anisotropic structures in situ, allowing a minimally-invasive application via injection. Synthetic, magnetically responsive, rod-shaped microgels are locally aligned and fixed by a biocompatible surrounding hydrogel, creating a hybrid anisotropic hydrogel (Anisogel), of which the physical, mechanical, and chemical properties can be tailored. The microgels are rendered cell-adhesive with GRGDS and incorporated either inside a cell-adhesive fibrin or bioinert poly(ethylene glycol) hydrogel to strongly interact with fibroblasts. GRGDS-modified microgels inside a fibrin-based Anisogel enhance fibroblast alignment and lead to a reduction in fibronectin production, indicating successful replacement of structural proteins. In addition, YAP-translocation to the nucleus increases with the concentration of microgels, indicating cellular sensing of the overall anisotropic mechanical properties of the Anisogel. For bioinert surrounding PEG hydrogels, GRGDS-microgels are required to support cell proliferation and fibronectin production. In contrast to fibroblasts, primary nerve growth is not significantly affected by the biomodification of the microgels. In conclusion, this approach opens new opportunities towards advanced and complex aECMs for tissue regeneration.
- ItemMicrofluidic fabrication of polyethylene glycol microgel capsules with tailored properties for the delivery of biomolecules(Cambridge : RSC, 2017) Guerzoni, Luis P. B.; Bohl, Jan; Jans, Alexander; Rose, Jonas C.; Koehler, Jens; Kuehne, Alexander J. C.; De Laporte, LauraMicrofluidic encapsulation platforms have great potential not only in pharmaceutical applications but also in the consumer products industry. Droplet-based microfluidics is increasingly used for the production of monodisperse polymer microcapsules for biomedical applications. In this work, a microfluidic technique is developed for the fabrication of monodisperse double emulsion droplets, where the shell is crosslinked into microgel capsules. A six-armed acrylated star-shaped poly(ethylene oxide-stat-propylene oxide) pre-polymer is used to form the microgel shell after a photo-initiated crosslinking reaction. The synthesized microgel capsules are hollow, enabling direct encapsulation of large amounts of multiple biomolecules with the inner aqueous phase completely engulfed inside the double emulsion droplets. The shell thickness and overall microgel sizes can be controlled via the flow rates. The morphology and size of the shells are characterized by cryo-SEM. The encapsulation and retention of 10 kDa FITC-dextran and its microgel degradation mediated release are monitored by fluorescence microscopy. © 2017 The Royal Society of Chemistry.
- ItemSynthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension(Columbus, Ohio : American Chemical Society, 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, LauraAn 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.
- ItemHigh-Throughput Production of Micrometer Sized Double Emulsions and Microgel Capsules in Parallelized 3D Printed Microfluidic Devices(Basel : MDPI, 2019) Jans, Alexander; Lölsberg, Jonas; Omidinia-Anarkoli, Abdolrahman; Viermann, Robin; Möller, Martin; De Laporte, Laura; Wessling, Matthias; Kuehne, Alexander J. C.Double emulsions are useful geometries as templates for core-shell particles, hollow sphere capsules, and for the production of biomedical delivery vehicles. In microfluidics, two approaches are currently being pursued for the preparation of microfluidic double emulsion devices. The first approach utilizes soft lithography, where many identical double-flow-focusing channel geometries are produced in a hydrophobic silicone matrix. This technique requires selective surface modification of the respective channel sections to facilitate alternating wetting conditions of the channel walls to obtain monodisperse double emulsion droplets. The second technique relies on tapered glass capillaries, which are coaxially aligned, so that double emulsions are produced after flow focusing of two co-flowing streams. This technique does not require surface modification of the capillaries, as only the continuous phase is in contact with the emulsifying orifice; however, these devices cannot be fabricated in a reproducible manner, which results in polydisperse double emulsion droplets, if these capillary devices were to be parallelized. Here, we present 3D printing as a means to generate four identical and parallelized capillary device architectures, which produce monodisperse double emulsions with droplet diameters in the range of 500 µm. We demonstrate high throughput synthesis of W/O/W and O/W/O double emulsions, without the need for time-consuming surface treatment of the 3D printed microfluidic device architecture. Finally, we show that we can apply this device platform to generate hollow sphere microgels.
- ItemAn Injectable Hybrid Hydrogel with Oriented Short Fibers Induces Unidirectional Growth of Functional Nerve Cells(Weinheim : Wiley-VCH, 2017) Omidinia-Anarkoli, Abdolrahman; Boesveld, Sarah; Tuvshindorj, Urandelger; Rose, Jonas C.; Haraszti, Tamás; De Laporte, LauraTo regenerate soft aligned tissues in living organisms, low invasive biomaterials are required to create 3D microenvironments with a structural complexity to mimic the tissue's native architecture. Here, a tunable injectable hydrogel is reported, which allows precise engineering of the construct's anisotropy in situ. This material is defined as an Anisogel, representing a new type of tissue regenerative therapy. The Anisogel comprises a soft hydrogel, surrounding magneto-responsive, cell adhesive, short fibers, which orient in situ in the direction of a low external magnetic field, before complete gelation of the matrix. The magnetic field can be removed after gelation of the biocompatible gel precursor, which fixes the aligned fibers and preserves the anisotropic structure of the Anisogel. Fibroblasts and nerve cells grow and extend unidirectionally within the Anisogels, in comparison to hydrogels without fibers or with randomly oriented fibers. The neurons inside the Anisogel show spontaneous electrical activity with calcium signals propagating along the anisotropy axis of the material. The reported system is simple and elegant and the short magneto-responsive fibers can be produced with an effective high-throughput method, ideal for a minimal invasive route for aligned tissue therapy.