![]() A systems-based view of development and regeneration may provide suitable therapeutic alternatives. However, it still remains very difficult to alter the expression of genes to rebuild damaged tissue in humans, especially when considering the use of controversial treatments such as gene therapy. Research over the last few decades has helped elucidate the strong dependence on the complex orchestration of multiple gene products in space and time. These processes involve complex interactions between the chemical and physical realms. The study of development and regeneration enhances our understanding of the natural mechanisms for the building and rebuilding of organisms, from the level of the single cell to the entire body plan. ![]() Understanding the mechanisms by which native and applied EFs direct development and repair will enable current and future therapeutic applications to be optimized. Here we review the generation of endogenous EFs, the results of their alteration, and the mechanisms by which cells may sense these weak fields. However, under more rigorously controlled conditions in vitro, applied EFs induce cellular polarity and direct migration and outgrowth. EFs are thought to influence many different processes in vivo. Although clinical trials, spanning a course of decades, have shown that applied EFs enhance healing of chronic wounds, the mechanisms by which cells sense and respond to these weak cues remains unknown. EFs are applied to humans in the clinic, to provide an overwhelming signal for the enhancement of healing of chronic wounds. Nullification of endogenous EFs with pharmacological agents or applied EFs of opposite polarity disturbs the aforementioned processes, while enhancement increases the rate of wound closure and the extent of regeneration. The fields are the result of polarized ion transport and current flow through electrically conductive pathways. Endogenous DC electric fields (EFs) are important, fundamental components of development, regeneration, and wound healing.
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