A Platform to Study the Effects of Electrical Stimulation on Immune Cell Activation During Wound Healing

Wound healing is a complex process involving diverse changes in multiple cell types where the application of electric fields has been shown to accelerate wound closure. To define the efficacy of therapies based on electric fields, it would be valuable to have a platform to systematically study the e...

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Bibliographic Details
Published in:Advanced biosystems 2019-10, Vol.3 (10), p.e1900106-n/a
Main Authors: Wang, Kaiping, Parekh, Udit, Ting, Jonathan K., Yamamoto, Natasha A. D., Zhu, Juan, Costantini, Todd, Arias, Ana Claudia, Eliceiri, Brian P., Ng, Tse Nga
Format: Article
Language:English
Subjects:
electrical stimulation
flexible electrodes
phosphorylation proteins
wound healing
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Summary:Wound healing is a complex process involving diverse changes in multiple cell types where the application of electric fields has been shown to accelerate wound closure. To define the efficacy of therapies based on electric fields, it would be valuable to have a platform to systematically study the effects of electrical stimulation (ES) upon the inflammation phase and the activation of signaling mediators. Here, an in vivo ES model in which flexible electrodes are applied to an animal model for monitoring inflammation in a wound is reported on. Subcutaneous implants of polyvinyl alcohol sponges elicit inflammation response as defined by the infiltration of leukocytes. The wound site is subjected to electric fields using two types of additively fabricated flexible electrode arrays. The sponges are then harvested for flow cytometry analysis to identify changes in the phosphorylation state of intracellular targets. This platform enables studies of molecular mechanisms, as it shows that an application of low‐frequency ES ≤0.5 Hz increases phosphorylation of Erk proteins in recruited leukocytes, identifying a signaling pathway that is activated during the healing process. A novel platform is presented, combining metal–organic hybrid flexible electrode arrays with an in vivo wound model and flow cytometry‐based assays which can systematically probe the molecular mechanisms underlying accelerated wound healing by electrical stimulation. The platform is used to show that the Erk pathway is preferentially activated in immune cells at a wound site, upon low‐frequency electrical stimulation.
ISSN:2366-7478
2366-7478
DOI:10.1002/adbi.201900106