Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.
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Anisotropic, porous hydrogels templated by lyotropic chromonic liquid crystals
Approaches to control the microstructure of hydrogels enable the control of cell–material interactions and the design of stimuli-responsive materials. We report a versatile approach for the synthesis of anisotropic polyacrylamide hydrogels using lyotropic chromonic liquid crystal (LCLC) templating. The orientational order of LCLCs in a mold can be patterned by controlling surface anchoring conditions, which in turn patterns the polymer network. The resulting hydrogels have tunable pore size and mechanical anisotropy. For example, the elastic moduli measured parallel and perpendicular to the LCLC order are 124.9 ± 6.4 kPa and 17.4 ± 1.1 kPa for a single composition. The resulting anisotropic hydrogels also have 30% larger swelling normal to the LCLC orientation than along the LCLC orientation. By patterning the LCLC order, this anisotropic swelling can be used to create 3D hydrogel structures. These anisotropic gels can also be functionalized with extracellular matrix (ECM) proteins and used as compliant substrata for cell culture. As an illustrative example, we show that the patterned hydrogel microstructure can be used to direct the orientation of cultured human corneal fibroblasts. This strategy to make anisotropic hydrogels has potential for enabling patternable tissue scaffolds, soft robotics, or microfluidic devices.
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- Award ID(s):
- 1663367
- NSF-PAR ID:
- 10208796
- Date Published:
- Journal Name:
- Journal of Materials Chemistry B
- Volume:
- 8
- Issue:
- 31
- ISSN:
- 2050-750X
- Page Range / eLocation ID:
- 6988 to 6998
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Properties of particulate-filled polymer matrix composites are highly dependent on the spatial position, orientation and assembly of the particles throughout the matrix. External fields such as electric and magnetic have been individually used to orient, position and assemble micro and nanoparticles in polymer solutions and their resulting material properties were investigated, but the combined effect of using more than one external field on the material properties has not been studied in detail. Applying different configurations of electric and magnetic fields on geometrically and magnetically anisotropic particulates can produce varying microarchitectures with a range of material properties. Experimentally and with simulations, we systematically probe the effect of combined electric and magnetic fields on the microstructure formation of geometrically and magnetically anisotropic barium hexaferrite (BHF) in polydimethylsiloxane (PDMS). The magnetic and dielectric properties resulting from different microstructures are characterized and microstructure-property relationships are analyzed. Our results demonstrate that a variety of microarchitectures can be produced using multi-field processing depending on the nature of the applied external field. For example, the application of an electric field creates macro-chains where the orientation of the BHF stacks inside the macro-chains is random. On the other hand, application of a magnetic field rotates the BHF stacks within the macro-chain in the direction dictated by the magnetic field. In simulations, the dielectrophoretic, magnetic, and viscous forces and torques acting on the particles show that particle anisotropies are central to the ability to control orientation along the orthogonal magnetic and geometric axes, mirroring experimental results. The authors refer to the ability to manipulate particle orientation along orthogonal axes as ‘orthogonal control’. Using this technique, not only are a variety of microstructures possible, but also a range of dielectric and magnetic properties can result. For example, for 1 vol% BHF-PDMS composites, the experimental dielectric permittivity is found to vary from 2.84 to 5.12 and the squareness ratio (remnant magnetization over saturation magnetization) is found to vary from 0.55 to 0.92 (from 0.52 to 0.99 in simulations) depending on the applied external stimuli. The ability to predict and produce a variety of microstructures with a range of properties from a single material set will be particularly beneficial for resin pool based additive manufacturing and 3D printing.
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null (Ed.)Hydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.84 kPa), physiologic (8.98 ± 1.29 kPa) and fibrotic (18.27 ± 3.17 kPa) cardiac tissues. The average pore diameter and hydrogel swelling were seen to decrease with increasing substrate stiffness. Cardiomyocytes cultured within soft embryonic gels demonstrated enhanced cell spreading, elongation, and network formation, while a progressive increase in gel stiffness diminished these behaviors. Cell viability decreased with increasing hydrogel stiffness. Furthermore, cells in fibrotic gels showed enhanced protein expression of the characteristic cardiac stress biomarker, Troponin-I, while reduced protein expression of the cardiac gap junction protein, Connexin-43, in comparison to cells within embryonic gels. The results from this study demonstrate the role that 3D substrate stiffness has on cardiac tissue formation and its implications in the development of complex matrix remodeling-based conditions, such as myocardial fibrosis.more » « less
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Abstract Cracks are typically associated with the failure of materials. However, cracks can also be used to create periodic patterns on the surfaces of materials, as observed in the skin of crocodiles and elephants. In synthetic materials, surface patterns are critical to micro‐ and nanoscale fabrication processes. Here, a strategy is presented that enables freely programmable patterns of cracks on the surface of a polymer and then uses these cracks to pattern other materials. Cracks form during deposition of a thin film metal on a liquid crystal polymer network (LCN) and follow the spatially patterned molecular order of the polymer. These patterned sub‐micrometer scale cracks have an order parameter of 0.98 ± 0.02 and form readily over centimeter‐scale areas on the flexible substrates. The patterning of the LCN enables cracks that turn corners, spiral azimuthally, or radiate from a point. Conductive inks can be filled into these oriented cracks, resulting in flexible, anisotropic, and transparent conductors. This materials‐based processing approach to patterning cracks enables unprecedented control of the orientation, length, width, and depth of the cracks without costly lithography methods. This approach promises new architectures of electronics, sensors, fluidics, optics, and other devices with micro‐ and nanoscale features.
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D0TB00904K
