ABSTRACT
Engineers believe that anything that is not expressly forbidden by the laws of physics is possible. Thus, an engineering approach to regeneration focuses not on whether the complex regeneration is possible, but on how it is to be accomplished. Here, we discuss a new approach: learning to intervene in the algorithms that guide large-scale pattern regulation. One of the ways in which cells coordinate their activity toward the maintenance and repair of complex anatomical structures is through bioelectrical networks. Voltage gradients produced in vivo by ion channels and pumps, and propagated through electrical synapses known as gap junctions, are used by cell groups to process global patterning information. Recent work has resulted in state-of-the-art tools that facilitate linkage between ionic controls and downstream molecular-genetic pathways, and enable control of endogenous voltage gradients. Experimental modulation of these bioelectric circuits moreover has been shown to induce organ formation and repair as a kind of top–down master regulator. Here, we review the past work on developmental bioelectricity in limb regeneration, discuss modern advances in the field, and provide a perspective on the technological and conceptual advances that are required to crack the bioelectric code and enable limb regeneration.
