Come together: On-chip bioelectric wound closure

Abstract

There is a growing interest in bioelectric wound treatment and electrotaxis, the process by which cells detect an electric field and orient their migration along its direction, has emerged as a potential cornerstone of the endogenous wound healing response. Despite recognition of the importance of electrotaxis in wound healing, no experimental demonstration to date has shown that the actual closing of a wound can be accelerated solely by the electrotaxis response itself, and in vivo systems are too complex to resolve cell migration from other healing stages such as proliferation and inflammation. This uncertainty has led to a lack of standardization between stimulation methods, model systems, and electrode technology required for device development. In this paper, we present a ‘healing-on-chip’ approach that is a standardized, low-cost, model for investigating electrically accelerated wound healing. Our device provides a biomimetic convergent field geometry that more closely resembles actual wound fields. We validate this device by using electrical stimulation to close a 1.5 mm gap between two large (30 mm2) layers of primary skin keratinocyte to completely heal the gap twice as quickly as in an unstimulated tissue. This demonstration proves that convergent electrotaxis is both possible and can accelerate healing and offers an accessible ‘healing-on-a-chip’ platform to explore future bioelectric interfaces.