ANNALS OF BIOMEDICAL ENGINEERING 4, 1--5 (1976)

Electrical Promotion of Soft Tissue Repairs

J. J. KONIKOFF
Research Division, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, New Jersey 07110

Received August 24, 1975

A short experiment was conducted to determine if levels of current similar to those

used in the electric enhancement of bone repair would also promote soft tissue repair.
Two full-thickness skin incisions were made in the lumbar region of each of five rabbits,
one on either side of the spine, and a 20 ~A current generator was connected to one
incision on each animal with a sham generator connected to the incision on the other
side. After 7 days, tensile testing of excised skin/incisions indicated that the electrically
treated wounds required a mean 53% increase in loading (0.99 to 225%) over the controls
before separation occurred at the incision.

INTRODUCTION

It has been shown that a current of injury will inevitably arise as a result of
tissue damage in the living body. This current is the result of the disruption of the
cellular membrane integrity which permits the chemical milieu to be altered as
the ionic contents of the cells spill out into the extracellular fluid. Burr et al.
(1935) and Barnes (1945), among others, have postulated that this bioelectric
current contributes in some manner to the process of wound repair. Recently,
applications of externally generated weak electric fields have been used to promote
bone regeneration (Friedenberg et al., 1971; Lavine et al., 1972, 1974; Bassett,
1971; and Bassett et al., 1974) and soft tissue repair (Tyurlikova and Lassi,
1967; Assimacopoulos, 1968; and Wolcott et al., 1969). The currents developed b y
these electric fields may be considered externally generated correlates of the
internally generated current of injury, thus inferentially supporting the causal
role of the current of injury in wound repair.
Successful bone regeneration and/or reunion has occurred at an electric current
flow ranging from 3.5 to 30 uA, whereas the successful promotion of soft tissue
healing (decubitus ulcers, skin defects) is reported at current strengths of 100 to
800 pA. The reason for the great disparity in the levels of applied current selected
for soft tissue repair and hard tissue repair is not apparent from the published
reports.
As a result, a feasibility study was designed to examine the effect of applying
a dc current of 20 uA to full-thickness skin incisions in rabbits. This level of current
flow was selected because it lies in the median range of values of applied current
found successful in bone repair studies.

Copyright ~ 1976 by AcademicPress, Inc.

All rights of reproduction in nny form reserved.
 J. J. K O N I K O F F

CONTROL '~ ~ ~/~'-J' y' EXPERIMENTAL

j CATHOOE OVE ,NC,S,O.

~" BATTERIES
,-q " ~ ANODE-SUBCUTANEOUSLY

U "%
Fro. 1. Sketch illustrating placement of stimulators on experimental animal.

E X P E R I M E N T A L PROTOCOL

Studies were conducted on ten New Zealand albino rabbits weighing approxi-
mately 289 kg each. The animals were prepared for surgery by first clipping, then
shaving the hair from the skin on their dorsal sides. The animals were then anes-
thesized by an intravenous administration of veterinary grade sodium pentabarbi-
tM through a vein in one ear and the exposed skin was then cleaned with surgical
soap followed by a liberal application of bactericidal eoncentrationn (1:750) of
benzalkonium chloride. Under sterile surgical procedures, full-thickness skin
incisions were made in the lumbar region slightly lateral to the dorsal midline from
about the 7th to the 10th thoracic vertebrae on either side of the spine. These
incisions were approximately 2.0 cm long. A control incision was made on the
left side of the spine and the experimental incision on the right side of the same
animal. Four interrupted sutures (mereilene 4.0) were used to close the incisions
(Fig. 1).
A specially designed de current generator was constructed and is shown in
Figs. 2 and 3. The design is a modification of the experimental power unit de-
scribed by Lavine, Lustrin, and Shamos (1969). It consisted of two miniature
batteries (Model RM625) connected in series with a suitable resistor to permit

5.OV (-)
MIM
AM CERO-@
TER
0-30/~a (+)
t,

150 KQ,

Fig. 2. Wiring diagram, de stimtfl~tor.

 ENHANCED SOFT TISSUE REPAIR

RM625
BATTERIES

//j,,~ ~ ~SI1ROB=ER

~ V INSULATED LEAO
ALLIGATOR CLIP
<--- pt SCREEN
RESISTOR ~,.
150 g ~
6
9~- No. 2 8 go
Pt WIRE

Fla. 3. Assembled de stimulator and electrodes.

a continuous current flow of a b o u t 20 #A. An alligator clip was placed in one of

the leads for monitoring. T h e leads were insulated between the batteries and the
electrodes. The negative lead t e r m i n a t e d in a section of p l a t i n u m gauze 1.0 X2.5
cm. This electrode was placed over the incision and secured b y four sutures
(mcrcilene 4.0), one in each corner. T h e other lead was connected to a 2.0 cm
length of # 28 ga p l a t i n u m wire which formed the positive electrode. This electrode
was situated subcutaneously (through a stab wound) a p p r o x i m a t e l y 4.0 cm distal
to the surfacedocated negative electrode. A duplicate s t i m u l a t o r containing
inoperative batteries was placed in a like m a n n e r over tile control incision. T h e
stimulators were held in place by "belly b a n d s " constructed b y wrapping surgical
gauze around the animal's b o d y with the device fixed in position b y the gauze.
T h e device and its fixation b a n d was positioned proximal to the test incisions.
Following surgery and fixation of the stimulators, the animals were returned to
their individual cages and allowed full activity. These systems were left in place
for 7 days. An electrolytic solution (Beckman Electrolyte Gel) was m a i n t a i n e d
at the site of the negative electrode (Pt gauze) in order t h a t a low-resistenee p a t h
could be m a i n t a i n e d between the electrode and skin during this time. Five of the
experimental animals were withdrawn from the s t u d y due to either a failure in the
stimulating device or an infection at the site of incision.

TABLE l
RangeofCm'rents

Animal Current (#A) Mean

no. current
Mini- Maxi- (~A)
I~unl IiIUnl

l 20 25 23.6
2 19 21 19.3
3 18 20 19.0
4 20 26 22.4
5 16 24 20.9
4 J. J. KONIKOFF

TABLE 2
Effects of Weak Currents on Wound Healing

Animal Healing Load to rupture Expt'l/ Mean Mean

no. time control current current
(days) Control Experi- (~A) density
mental (~A/cm2)

1 7 725 1630 2.25 23.6 9.4

2 740 741 1.00 19.8 7.7
3 885 878 0.99 19.0 7.6
4 775 1631 2.11 22.4 9.0
5 860 1240 1.44 20.9 8.4

Mean values 797 1244 1.53 21.0 8.4

Currents were monitored daily on each animal b y inserting a Simpson Model

260-6 Portable V.O. milliameter into the circuit between the alligator clip and the
resistor/Pt wire assembly (see Fig. 3). T h e range of values is shown in Table 1.
After the experiment duration the surviving experimentals were sacrificed using
massive iv doses of Pentothal and generous sections of skin containing the experi-
ment and control incisions were removed. These were t r i m m e d to sections 1.6 X 3.0
em with the incision comprising the 1.6 em width. T h e specimen was clamped
between the jaws of a Thwing-Albert Eleetrotensiometer initially separated b y a
distance of 1.0 em with the incision perpendicular to the direction of pull. T h e
specimen was held in place firmly, with no slippage, b y pieces of fine-grade emery
cloth cemented to the inner faces of the steel rectangular clamps (jaws) of the pull
tester. The tensile testing was conducted b y a cross-head speed of 1.0 em/min.
Normal skin samples were also tested to investigate the validity of establishing
the left incision as the control and the right side experimental. Four 1.6X3.0 em
full-thickness sections of skin were removed from the backs of two animals proxi-
mal to the site of the surgically induced incisions and subjected to tensile testing
in the same manner as the test sections. Two sections each were taken from the
left and right side. These sections averaged 1.8 m m in thickness. The normal
healing load was determined to be 2946 and 2929 g for the left sides and 2934 and
2948 g for the right sides.
RESULTS AND DISCUSSION
Table 2 summarizes the data obtained during the tensile testing. The infor-
mation presented is the mean of five experiments comparing the electrically
treated wounds with the control. A mean 53 % increase in the wound strength after
7 days was measured in the electrically treated incisions. The values for the ratio
of electrically treated vs the nontreated incisions in the five animals ranged from
0.99 to 2.25. The mean value of applied current density ranged from 7.6 to 9.4
ttA/em 2 with a mean value of 8.4 ~ A / e m s. Although the data indicate that higher
current densities yield greater tensile strength, they are not statistically significant.
Thus, no conclusions can be drawn relative to the relationship between current
density and healing.
 ENHANCED SOFT TISSUE REPAIR

H o w e v e r , a l t h o u g h t h e small n u m b e r of samples decreased t h e overall statisti-

cal c e r t a i n t y of the effect of applied currents on healing in this p r e l i m i n a r y s t u d y ,
t h e application of the Wileoxon n o n p a r a m e t r i c test (1945) indicates t h a t t h e
p r o b a b i l i t y of t h e increased s t r e n g t h of the t r e a t e d incisions being due to c h a n c e
is less t h a n 10%. Therefore, t h e e n h a n c e m e n t of w o u n d s t r e n g t h b y electric
s t i m u l a t i o n as described in this r e p o r t has a g r e a t e r t h a n 9 0 % p r o b a b i l i t y of
being beneficial.
Thus, on a gross level it is s h o w n t h a t similar values of c u r r e n t flow do achieve
similar results in b o t h soft and h a r d tissue. I t is n o t k n o w n w h e t h e r these values
are o p t i m u m for each t y p e of tissue. I n d e e d , until t h e m e c h a n i s m is fully u n d e r -
stood, it will n o t be k n o w n w h e t h e r there is an o p t i m u m value. T o this end,
additional studies are c u r r e n t l y u n d e r way.

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