Abstract
Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body’s regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting “blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation”. In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.
Highlights
Another method, tried in the late 1960s and early 70s, was low voltage electricity
It has been shown that disrupting normal electrical fields in tissues surrounding the neural tube during chick embryogenesis causes severe developmental deformities; a cut in the skin short-circuits transepithelial potential differences and gives rise to injury current flow that plays an important role in initiating dermal healing; immediately following amputation of a newt limb elevated levels of electrical current emanate from the amputated stump for 10–14 days, and as the limb regrows levels decrease to pre-amputation levels
In the middle of the last century, these observations led researchers to experiment with the application of electrical current to stimulate healing and regeneration in bone, skin, nerves and even whole limbs
Summary
Another method, tried in the late 1960s and early 70s, was low voltage electricity. In 1972, an Orthopedic Surgeon, Robert Becker published a landmark article in the journal Nature[13] in which he reported that he had induced partial limb regeneration, in a rat limb amputation model, using low voltage direct current (DC) electrical stimulation. Libbin et al later reproduced Becker’s experiments, but were more careful describing their observations, and emphasized the important role “mechanical factors” might play in the observed regenerative response[16] Stemming partially from this early work, electrical stimulation was subsequently developed and is used widely today in clinical applications to heal dermal wounds, promote regeneration of nerves in the peripheral and central nervous systems, and to treat a variety of different bone related diseases like osteoporosis, osteoarthrosis, nonunion fractures, and to promote the integration of implanted biomaterials in orthopedics (reviewed in[17]). In recent years a great deal of research has focused on unraveling the underlying mechanisms of electrical stimulation (ES) at a cellular and subcellular level using in vitro model systems These have shown that ES influences stem and progenitor cell behavior, increasing cell proliferation, differentiation, matrix formation and migration. In contrast to the above cited in vitro studies, in the present study we delivered low voltage direct current (DC) electrical stimulation to the stumps of amputated rat forelimbs and used histology and immunohistochemistry to assess the resulting healing and regeneration response
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