Freeform Perfusable Microfluidics Embedded in Hydrogel Matrices.
Ontology highlight
ABSTRACT:
SUBMITTER: Stumberger G
PROVIDER: S-EPMC6316925 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π-π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K+ ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.
| S-EPMC10336844 | biostudies-literature
Project description:The kinetics of supramolecular bindings are fundamentally important for molecular motions and spatial-temporal distributions in biological systems, but have rarely been employed in preparing artificial materials. This report proposes a bio-inspired concept to regulate dynamic gradients through the coupled supramolecular binding and diffusion process in receptor-embedded hydrogel matrices. A new type of hydrogel that uses cyclodextrin (CD) as both the gelling moiety and the receptors is prepared as the diffusion matrices. The diffusible guest, 4-aminoazobenzene, quickly and reversibly binds to matrices-bound CD during diffusion and generates steeper gradients than regular diffusion. Weakened bindings induced through UV irradiation extend the gradients. Combined with numerical simulation, these results indicate that the coupled binding-diffusion could be viewed as slowed diffusion, regulated jointly by the binding constant and the equilibrium receptor concentrations, and gradients within a bio-relevant extent of 4?mm are preserved up to 90?h. This report should inspire design strategies of biomedical or cell-culturing materials.
| S-EPMC4981054 | biostudies-literature
Project description:Hydrogels are networks of hydrophilic polymer chains that are swollen with water, and they are useful for a wide range of applications because they provide stable niches for immobilizing proteins and cells. We report here the marriage of hydrogels with digital microfluidic devices. Until recently, digital microfluidics, a fluid handling technique in which discrete droplets are manipulated electromechanically on the surface of an array of electrodes, has been used only for homogeneous systems involving liquid reagents. Here, we demonstrate for the first time that the cylindrical hydrogel discs can be incorporated into digital microfluidic systems and that these discs can be systematically addressed by droplets of reagents. Droplet movement is observed to be unimpeded by interaction with the gel discs, and gel discs remain stationary when droplets pass through them. Analyte transport into gel discs is observed to be identical to diffusion in cases in which droplets are incubated with gels passively, but transport is enhanced when droplets are continually actuated through the gels. The system is useful for generating integrated enzymatic microreactors and for three-dimensional cell culture. This paper demonstrates a new combination of techniques for lab-on-a-chip systems which we propose will be useful for a wide range of applications.
| S-EPMC3365348 | biostudies-other
Project description:Electroactive hydrogels that exhibit large deformation in response to an electric field have received significant attention as a potential actuating material for soft actuators and artificial muscle. However, their mechanical actuation has been limited in simple bending or folding due to uniform electric field modulation. To implement complex movements, a pre-program, such as a hinge and a multilayer pattern, is usually required for the actuator in advance. Here, we propose a reprogrammable actuating method and sophisticated manipulation by using multipolar three-dimensional electric field modulation without pre-program. Through the multipolar spatial electric field modulator, which controls the polarity/intensity of the electric field in three-dimensions, complex three-dimensional (3D) actuation of single hydrogels are achieved. Also, air bubbles generated during operation in the conventional horizontal configuration are not an issue in the proposed new vertical configuration. We demonstrate soft robotic actuators, including basic bending mechanics in terms of controllability and reliability, and several 3D shapes having positive and negative curvature can easily be achieved in a single sheet, paving the way for continuously reconfigurable materials.
| S-EPMC7015902 | biostudies-literature
Project description:Fiber-based materials with microchannels have drawn considerable attention in recent years owing to their ability to mimic intrinsic morphologies of living tissues. Folded morphologies, which are common in vivo, such as in skeletal muscle capillaries and intestine luminal endoderm, play important roles in the achievement of tissue functions. Here, microfibers with folded hollow channels are fabricated. Channel morphologies, such as straight-folded, double-folded and double-helical channels, can be regulated by adjusting flow conditions in the microfluidic devices. To further demonstrate the potential to be used in tissue engineering, intestine and skeletal muscle constructs are fabricated using these microfibers as building blocks. Furthermore, the properties of perfusability, permeability, cytocompatibility and weavability of the microfibers are evaluated. The asymmetric molecular distributions in the microfibers provide promising platforms for the study of nutrient exchange and energy supplement between normal and tortuous tissues. The new features of biofibers and proof-of-concept of tissue constructs with folded morphologies may contribute to the development of regenerative medicine and drug screening in the future.
| S-EPMC9081586 | biostudies-literature
Project description:Hydrogels have numerous biomedical applications including synthetic matrices for cell culture and tissue engineering. Here we report the development of hydrogel based multifunctional matrices that not only provide three-dimensional structural support to the embedded cells but also can simultaneously provide potentially beneficial dynamic mechanical and electrical cues to the cells. A unique aspect of these matrices is that they undergo reversible, anisotropic bending dynamics in an electric field. The direction and magnitude of this bending can be tuned through the hydrogel crosslink density while maintaining the same electric potential gradient, allowing control over the mechanical strain imparted to the cells in a three-dimensional environment. The conceptual design of these hydrogels was motivated through theoretical modeling of the osmotic pressure changes occurring at the gel-solution interfaces in an electric field. These electro-mechanical matrices support survival, proliferation, and differentiation of stem cells. Thus, these new three-dimensional in vitro synthetic matrices, which mimic multiple aspects of the native cellular environment, take us one step closer to in vivo systems.
| S-EPMC3837709 | biostudies-literature
Project description:Biomolecular signaling is of utmost importance in governing many biological processes such as the patterning of the developing embryo where biomolecules regulate key cell-fate decisions. In vivo, these factors are presented in a spatiotemporally tightly controlled fashion. Although state-of-the-art microfluidic technologies allow precise biomolecule delivery in time and space, long-term (stem) cell culture at the micro-scale is often far from ideal due to medium evaporation, limited space for cell growth or shear stress. To overcome these challenges, we here introduce a concept based on hydrogel microfluidics for decoupling conventional, macro-scale cell culture from precise biomolecule delivery through a gel layer. We demonstrate the spatiotemporally controlled neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid gradients. This technique should be useful for testing the effect of dose and timing of biomolecules, singly or in combination, on stem cell fate.
| S-EPMC3964519 | biostudies-literature
Project description:Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of metastatic cascade still remains a challenge. We here developed an in vitro model of extravasation composed of (i) a single channel-based 3D cell laden hydrogel representative of the metastatic site, (ii) a circulation system recapitulating the bloodstream where CTCs can flow. Two polymers (i.e., fibrin and alginate) were tested and compared in terms of mechanical and biochemical proprieties. Computational fluid-dynamic (CFD) simulations were also performed to predict the fluid dynamics within the polymeric matrix and, consequently, the optimal culture conditions. Next, once the platform was validated through perfusion tests by fluidically connecting the hydrogels with the external circuit, highly metastatic breast cancer cells (MDA-MB-231) were injected and exposed to physiological wall shear stress (WSS) conditions (5 Dyn/cm2) to assess their migration toward the hydrogel. Results indicated that CTCs arrested and colonized the polymeric matrix, showing that this platform can be an effective fluidic system to model the first steps occurring during the metastatic cascade as well as a potential tool to in vitro elucidate the contribution of hemodynamics on cancer dissemination to a secondary site.
| S-EPMC7690854 | biostudies-literature
Project description:Stimuli-responsive hydrogels have a wide range of potential applications in microfluidics, which has drawn great attention. Double cross-linked hydrogels are very well suited for this application as they offer both stability and the required responsive behavior. Here, we report the integration of poly(N-isopropylacrylamide) (PNiPAAm) hydrogel with a permanent cross-linker (N,N'-methylenebisacrylamide, BIS) and a redox responsive reversible cross-linker (N,N'-bis(acryloyl)cystamine, BAC) into a microfluidic device through photopolymerization. Cleavage and re-formation of disulfide bonds introduced by BAC changed the cross-linking densities of the hydrogel dots, making them swell or shrink. Rheological measurements allowed for selecting hydrogels that withstand long-term shear forces present in microfluidic devices under continuous flow. Once implemented, the thiol-disulfide exchange allowed the hydrogel dots to successfully capture and release the protein bovine serum albumin (BSA). BSA was labeled with rhodamine B and functionalized with 2-(2-pyridyldithio)-ethylamine (PDA) to introduce disulfide bonds. The reversible capture and release of the protein reached an efficiency of 83.6% in release rate and could be repeated over 3 cycles within the microfluidic device. These results demonstrate that our redox-responsive hydrogel dots enable the dynamic capture and release of various different functionalized (macro)molecules (e.g., proteins and drugs) and have a great potential to be integrated into a lab-on-a-chip device for detection and/or delivery.
| S-EPMC8780672 | biostudies-literature
Project description:Patterned deposition and 3D fabrication techniques have enabled the use of hydrogels for a number of applications including microfluidics, sensors, separations, and tissue engineering in which form fits function. Devices such as reconfigurable microvalves or implantable tissues have been created using lithography or casting techniques. Here, we present a novel open-microfluidic patterning method that utilizes surface tension forces to form hydrogel layers on top of each other, into a patterned 3D structure. We use a patterning device to form a temporary open microfluidic channel on an existing gel layer, allowing the controlled flow of unpolymerized gel in device-regions. After layer gelation and device removal, the process can be repeated iteratively to create multi-layered 3D structures. The use of open-microfluidic and surface tension-based methods to define the shape of each individual layer enables patterning to be performed with a simple pipette and with minimal dead-volume. Our method is compatible with unmodified (native) biological hydrogels, and other non-biological materials with precursor fluid properties compatible with capillary flow. With our open-microfluidic layer-by-layer fabrication method, we demonstrate the capability to build agarose, type I collagen, and polymer-peptide 3D structures featuring asymmetric designs, multiple components, overhanging features, and cell-laden regions.
| S-EPMC8018606 | biostudies-literature