Electrical Stimulation Increases Random Migration of Human Dermal
Department of Biomedical Engineering, The University of Akron, Akron, OH 44325-0302, USA; and
Meinig School of
Biomedical Engineering, Cornell University, Ithaca, NY, USA
(Received 16 January 2017; accepted 3 May 2017; published online 9 May 2017)
Associate Editor Michael Gower oversaw the review of this article.
Abstract—Exogenous electrical stimulation (ES) has been
investigated as a therapy for chronic wounds, as the skin
produces currents and electrical ﬁelds (EFs) during wound
healing. ES therapies operate by applying small EFs to the
skin to mimic the transepithelial potentials that occur during
the granulation phase of wound healing. Here, we investi-
gated the effect of short duration (10 min) ES on the
migration of HDFs using various magnitudes of physiolog-
ically relevant EFs. We modeled cutaneous injury by
culturing HDFs in custom chambers that allowed the
application of ES and then performed timelapse microscopy
on a standard wound model. Using MATLAB to process cell
coordinate data, we determined that the cells were migrating
randomly and ﬁt mean squared displacement data to the
persistent random walk equation using nonlinear least
squares regression analysis. Results indicated that applica-
tion of 25–100 mV/mm DC EFs to HDFs on either uncoated
or FN-coated surfaces demonstrated no signiﬁcant changes
in viability or proliferation. Of signiﬁcance is that the HDFs
increased random migration behavior under some ES con-
ditions even after 10 min, providing a mechanism to enhance
Keywords—Electrical stimulation, Wound healing, Fibrob-
Annually, $25 billion is spent in the United States
on wound healing treatments aﬀecting 6.5 million
These excessive costs result partly from
and other nonhealing wounds,
which are deﬁned as wounds that do not heal as ex-
pected within three months.
Given the health and
economic implications of wound healing treatments, a
need exists for a wound healing therapy that can be
applied to traumatic and nonhealing wounds of vary-
ing sizes, geometries, and anatomical locations. It has
been well documented that the skin presents endoge-
nous electrical ﬁelds (EFs) in the range of 30–100 mV
during wound healing.
Ions traveling across cells and
tissues result in polarization of the tissue and a mea-
surable direct current (DC) EF gradient over the span
of a skin wound.
This phenomenon results in what
has been termed a transepithelial electric potential, and
the EF values generally fall in the range of 1–100 mV/
during normal wound healing processes.
These endogenous EFs are thought to inﬂuence cellu-
lar division, proliferation, and migration.
Attempts have been made to exploit the concept of
transepithelial electrical potentials by using ES as a
therapy to enhance wound healing.
of these studies focus on the application of EFs with
corresponding microampere (lA) currents. Most
studies utilize custom electrotaxis chambers to apply
EFs within the range of 50–100 mV/mm to two-di-
mensional cell cultures,
while in three-dimensional
systems, conductive membranes are often used to ap-
Several groups report increased rates of
wound healing in the presence of EFs.
tionally, hyperphysiological EFs and ultrasound have
been applied clinically and have been successful in
enhancing wound healing.
Based on these reports,
hyperphysiological currents with associated physio-
logical EFs may also be beneﬁcial to wound healing.
At the foundation of cutaneous wound healing is
the concept of increased cell migration into the site of
injury. Human dermal ﬁbroblasts (HDFs) have been
identiﬁed as a crucial component in cutaneous wound
as wound healing prompts the arrival
of inﬂammatory cells and ﬁbroblasts. HDFs are
Address correspondence to Rebecca Kuntz Willits, Department
of Biomedical Engineering, The University of Akron, Akron,
OH 44325-0302, USA. Electronic mail: firstname.lastname@example.org
Annals of Biomedical Engineering, Vol. 45, No. 9, September 2017 (
2017) pp. 2049–2060
2017 Biomedical Engineering Society