Come together: On-chip bioelectric wound closure

Zajdel, Tom J.; Shim, Gawoon; Cohen, Daniel

doi:10.1016/j.bios.2021.113479

Cited by 30 publications

(28 citation statements)

References 45 publications

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“…This is particularly relevant in the growing space of electroceuticals and bioelectronic interfaces being developed to augment large-scale, multicellular processes such as skin healing. Here, there is already striking data of the potential for electric fields to improve re-epithelialization in vitro ( 9 , 84 ) and in vivo ( 23 , 24 , 85–87 ). For instance, we previously demonstrated that closure of the classic in vitro ‘scratch wound’ can be accelerated by at least 2x in vitro using field stimulation ( 9 ), while direct electrical stimulation in vivo of zebrafish tail injuries improved the regeneration process ( 24 ).…”

Section: Discussionmentioning

confidence: 96%

“…Here, there is already striking data of the potential for electric fields to improve re-epithelialization in vitro ( 9 , 84 ) and in vivo ( 23 , 24 , 85–87 ). For instance, we previously demonstrated that closure of the classic in vitro ‘scratch wound’ can be accelerated by at least 2x in vitro using field stimulation ( 9 ), while direct electrical stimulation in vivo of zebrafish tail injuries improved the regeneration process ( 24 ). This is a highly interdisciplinary area of research, where there is an increasing need to investigate how stimulation affects general collective cellular responses.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, externally directing collective cell migration should allow us to not only better understand these processes, but also to formally program and engineer them for applications in regenerative medicine and tissue engineering, where large scale cellular motion is necessary, such as in wound healing ( 4–9 ). Programming cell migration is increasingly feasible with myriad emerging approaches spanning chemotactic devices (cells migrate along chemical gradients) ( 8 , 10–14 ), light-induced, optogenetic modulation of signaling pathways ( 15–17 ), and bioelectric programming of cell migration through electrotaxis (cells migrate along electrical gradients) ( 9 , 18–24 ). However, a key challenge for any stimulation modality is understanding how global commands, such as ‘All Cells Migrate Rightward’, play out and drive cellular dynamics at the overall system or tissue level where 10,000+ cellular agents must coordinate at the macroscale.…”

Section: Introductionmentioning

confidence: 99%

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Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics

et al. 2022

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The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration ‘command’ differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate ‘rightward’ via electrotaxis. Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell–cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell–cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics

et al. 2022

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“…[70][71][72] In the current state-of-the-art, the implementation of DCs still relies on metal electrodes and agar bridges as electrochemical buffers. Even though several research groups have managed to miniaturize and innovate the stimulation setup, [73,74] few groups address the persistent need for electrode materials that allow DCs to be applied directly in tissue. In this context, the use of CPs is a new approach with promising prospects for generating constant current stimulation in a biocompatible process.…”

Section: Discussionmentioning

confidence: 99%

Leveraging Conducting Polymers and Hydrogels for Direct Current Stimulation

Ordonez¹,

Shaner²,

Matter³

et al. 2022

Preprint

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<p>The tunable electrical properties of conducting polymers (CPs), biocompatibility, fabrication versatility, and cost-efficiency make them an ideal coating material for stimulation electrodes in biomedical applications. Several biological processes like wound healing, neuronal regrowth, and cancer metastasis, which rely on constant electric fields, demand electrodes capable of delivering direct current stimulation (DCs) for long times without developing toxic electrochemical reactions. Recently, CPs such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) have demonstrated outstanding capability for delivering DCs without damaging cells in culture while not requiring intermediate buffers, contrary to the current research setups relying on noble-metals and buffering bridges. However, a clear understanding of how electrode design and CP synthesis influence DCs properties of these materials is still needed. This study demonstrates that various PEDOT-based CP coatings and hydrogels on rough electrodes can deliver DCs without substantial changes to the electrode and noticeable development of chemical byproducts depending on the electrode area and polymer thickness. A comprehensive analysis of the tested coatings is provided according to the desired application and available resources alongside a proposed explanation for the observed electrochemical behavior. The CPs tested herein can pave the way toward the widespread implementation of DCs as a therapeutic stimulation paradigm.</p>

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“…22,23 It is only recently that there has been more focus on electrotaxis-mediated group migration. 24,25 For instance, Zajdel et al 26 showed that two patterned monolayers of keratinocytes, with a 1.5 mm gap, can be influenced by an EF stimulus (i.e., 200 mV mm −1 ) and close the gap between the two epithelial sheets twice as fast as compared to non-stimulated controls. This work set an important precedent, and calls for further translational efforts to make EF-accelerated repair accessible to patients who are at risk for chronic wounds.…”

Section: Introductionmentioning

confidence: 99%

Bioelectronic microfluidic wound healing

Shaner

Savelyeva

Kvartuh

et al. 2022

Preprint

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This work delves into the impact of direct current (DC) stimulation on both healthy and diabetic in vitro wound healing models of keratinocytes, the most prevalent cell type of the skin. The augmentation of non-metal electrode materials and prudent microfluidic design allowed for a platform to study the effects of different sustained (12 hours DC) electric field configurations on wound closure dynamics. We found that electric guidance cues (≃ 200 mV/mm) enhance wound closure rate by nearly 3X for both healthy and diabetic-like keratinocyte sheets, compared to their respective controls. The motility-inhibited keratinocytes regained wound closure rates with stimulation (increase from 1.0 to 2.8 %/hr) comparable to healthy non-stimulated keratinocyte collectives (3.5 %/hr). Our results bring hope that electrical stimulation is a viable pathway to accelerate wound repair.

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Come together: On-chip bioelectric wound closure

Cited by 30 publications

References 45 publications

Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics

Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics

Leveraging Conducting Polymers and Hydrogels for Direct Current Stimulation

Bioelectronic microfluidic wound healing

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