The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow

Mansouri, Mehran; Ahmed, Adeel; Ahmad, Sarfraz; McCloskey, Molly C.; Joshi, Indranil M; Gaborski, Thomas R.; Waugh, Richard E.; McGrath, James L.; Day, Steven W.; Abhyankar, Vinay V.

doi:10.1002/adhm.202200802

Cited by 13 publications

(7 citation statements)

References 103 publications

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“…Although EK techniques such as EP and DEP are able to form densely packed layers of colloidal particles, there is little control in the particle packing order within these layers, highlighting a major area of improvement [67][68][69][70][71][72]. The combination of multiple EK techniques within the same system has allowed higher control, resulting in the patterning of colloidal particles into advanced structures [51,58,64].…”

Section: Hybrid Systems Employed For the Patterning Of Colloidsmentioning

confidence: 99%

“…Gels are an increasingly popular material for 3D cell cultures due to their biological and mechanical properties [124][125][126]. Gels are 3D networks able to assimilate large amounts of water and/or biological fluids, making them excellent options for applications that require a resemblance to biological tissue [67,[127][128][129]. Recent reports on the formation of patterns in gels using EK mechanisms are discussed in the following sections.…”

Section: Gelsmentioning

confidence: 99%

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Electropatterning—Contemporary developments for selective particle arrangements employing electrokinetics

et al. 2023

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The selective positioning and arrangement of distinct types of multiscale particles can be used in numerous applications in microfluidics, including integrated circuits, sensors and biochips. Electrokinetic (EK) techniques offer an extensive range of options for label‐free manipulation and patterning of colloidal particles by exploiting the intrinsic electrical properties of the target of interest. EK‐based techniques have been widely implemented in many recent studies, and various methodologies and microfluidic device designs have been developed to achieve patterning two‐ and three‐dimensional (3D) patterned structures. This review provides an overview of the progress in electropatterning research during the last 5 years in the microfluidics arena. This article discusses the advances in the electropatterning of colloids, droplets, synthetic particles, cells, and gels. Each subsection analyzes the manipulation of the particles of interest via EK techniques such as electrophoresis and dielectrophoresis. The conclusions summarize recent advances and provide an outlook on the future of electropatterning in various fields of application, especially those with 3D arrangements as their end goal.

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Section: Hybrid Systems Employed For the Patterning Of Colloidsmentioning

confidence: 99%

Section: Gelsmentioning

confidence: 99%

Electropatterning—Contemporary developments for selective particle arrangements employing electrokinetics

et al. 2023

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“…Microfluidic approaches are well-recognized as experimental tools that enable precise control over the cellular microenvironment. [44,70,71,72] Conventional microfluidic systems are permanently sealed, and the introduction of cells requires that they are included in the self-assembling gel solution or added through ancillary seeding channels. [73][74][75][76] Incorporating cells in the gel solution limits the parameter space (e.g., gelation temperature, ionic strength, pH, mechanical strain, or photoinitiator concentration) that can be used to control matrix properties.…”

Section: A Reversibly Sealed Microchannel Allows Direct Access To Mic...mentioning

confidence: 99%

Microengineering 3D Collagen Matrices with Tumor‐Mimetic Gradients in Fiber Alignment

Joshi,

Mansouri,

Ahmed

et al. 2023

Adv Funct Materials

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Collagen fibers in the 3D tumor microenvironment (TME) exhibit complex alignment landscapes that are critical in directing cell migration through a process called contact guidance. Previous in vitro work studying this phenomenon has focused on quantifying cell responses in uniformly aligned environments. However, the TME also features short‐range gradients in fiber alignment that result from cell‐induced traction forces. Although the influence of graded biophysical taxis cues is well established, cell responses to physiological alignment gradients remain largely unexplored. In this work, fiber alignment gradients in biopsy samples are characterized and recreated using a new microfluidic biofabrication technique to achieve tunable sub‐millimeter to millimeter scale gradients. This study represents the first successful engineering of continuous alignment gradients in soft, natural biomaterials. Migration experiments on graded alignment show that human umbilical vein endothelial cells (HUVECs) exhibit increased directionality, persistence, and speed compared to uniform and unaligned fiber architectures. Similarly, patterned MDA‐MB‐231 breast cancer cell aggregates exhibit biased migration toward increasing fiber alignment, suggesting a role for alignment gradients as a taxis cue. This user‐friendly approach, requiring no specialized equipment, is anticipated to offer new insights into the biophysical cues that cells interpret as they traverse the extracellular matrix (ECM), with broad applicability in healthy and diseased tissue environments.

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“…After quantifying relationships between CoA, porosity, and fiber density in our gels, we sought to quantify how cells respond to fiber alignment gradients in our microfluidic platform. Microfluidic approaches are well-recognized as experimental tools that enable precise control over the cellular microenvironment [64][65][66]. Conventional microfluidic systems are permanently sealed, and the introduction of cells requires that they are included in the self-assembling gel solution or added through ancillary seeding channels are used [67][68][69][70].…”

Section: A Reversibly Sealed Microchannel Allows Direct Access To Mic...mentioning

confidence: 99%

Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment

Joshi,

Mansouri,

Ahmed

et al. 2023

Preprint

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In the tumor microenvironment (TME), collagen fibers facilitate tumor cell migration through the extracellular matrix. Previous studies have focused on studying the responses of cells on uniformly aligned or randomly aligned collagen fibers. However, the in vivo environment also features spatial gradients in alignment, which arise from the local reorganization of the matrix architecture due to cell-induced traction forces. Although there has been extensive research on how cells respond to graded biophysical cues, such as stiffness, porosity, and ligand density, the cellular responses to physiological fiber alignment gradients have been largely unexplored. This is due, in part, to a lack of robust experimental techniques to create controlled alignment gradients in natural materials. In this study, we image tumor biopsy samples and characterize the alignment gradients present in the TME. To replicate physiological gradients, we introduce a first-of-its-kind biofabrication technique that utilizes a microfluidic channel with constricting and expanding geometry to engineer 3D collagen hydrogels with tunable fiber alignment gradients that range from sub-millimeter to millimeter length scales. Our modular approach allows easy access to the microengineered gradient gels, and we demonstrate that HUVECs migrate in response to the fiber architecture. We provide preliminary evidence suggesting that MDA-MB-231 cell aggregates, patterned onto a specific location on the alignment gradient, exhibit preferential migration towards increasing alignment. This finding suggests that alignment gradients could serve as an additional taxis cue in the ECM. Importantly, our study represents the first successful engineering of continuous gradients of fiber alignment in soft, natural materials. We anticipate that our user-friendly platform, which needs no specialized equipment, will offer new experimental capabilities to study the impact of fiber-based contact guidance on directed cell migration.

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The Modular µSiM Reconfigured: Integration of Microfluidic Capabilities to Study In Vitro Barrier Tissue Models under Flow

Cited by 13 publications

References 103 publications

Electropatterning—Contemporary developments for selective particle arrangements employing electrokinetics

Electropatterning—Contemporary developments for selective particle arrangements employing electrokinetics

Microengineering 3D Collagen Matrices with Tumor‐Mimetic Gradients in Fiber Alignment

Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment

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