Optimal bioelectric control accelerates collective wound healing

Effective wound healing relies on thousands of cells collectively migrating to close the gap. It is increasingly clear that part of this migration is driven by endogenous electrochemical fields which point towards the center of skin wounds and guide collective cell migration through "electrotaxis". Mounting evidence suggests exogenously applied electric fields can accelerate healing, but progress in this field has been limited by the use of brute-force, global stimulation strategies that are wound agnostic and reflect neither the collective nature of the healing process nor the dynamic nature of the wound geometry. Here, we develop an experimental system to study how monolayer mouse skin responds to spatiotemporally patterned electric fields. We first show that local electrical stimulation can produce near global cell migration responses arising from cell-cell mechanical adhesion. We apply this strategy to 2D circular wounds using a local ring electric field near the wound edge and reveal how to tune the timing of local stimulation to avoid cellular jamming. Finally, we integrate our findings with a biophysics-informed optimal control strategy to tune both when and where the electric field should be applied in time, resulting in dramatic improvements to healing.