6 results
Search Results
Now showing 1 - 6 of 6
- 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
- ItemPredicting the orientation of magnetic microgel rods for soft anisotropic biomimetic hydrogels(Cambridge : RSC Publ., 2020) Rose, Jonas C.; Fölster, Maaike; Kivilip, Lukas; Gerardo-Nava, Jose L.; Jaekel, Esther E.; Gehlen, David B.; Rohlfs, Wilko; De Laporte, LauraLiving multicellular organisms comprise a high degree of soft anisotropic tissues but the development of controlled artificial assembly processes to mimic them remains challenging. Therefore, injectable, polymeric, magneto-responsive microgel rods are fabricated to orient within a low magnetic field. The incorporated superparamagnetic nanoparticles induce local dipole moments, resulting in a total magnetic torque that endows microgels with different structural, mechanical, and biochemical properties. In this report, a predictive macroscopic model based on an ellipsoidal element dispersed in a Newtonian fluid is adjusted using experimental data, which enables the prediction of the orientation rate and the required magnetic field strength for various microgel design parameters and fluid viscosities. The ordered microgels are fixed by crosslinking of a surrounding hydrogel, and can be employed for a wide variety of applications where anisotropic composite hydrogels play a crucial role; for instance as adaptive materials or in biomedical applications, wherein the model predictions can reduce animal experiments. © 2019 The Royal Society of Chemistry.
- 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.
- 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.