Electro-stimulation, a promising therapeutic treatment modality for tissue repair: emerging roles of sulfated glycosaminoglycans as electro-regulatory mediators of intrinsic repair processes

Glycosaminoglycans (GAGs) are a family of diverse biomolecules that decorate proteoglycans in the glycocalyx and extracellular matrix of all cells. They exist as linear polysaccharide chains consisting of repeating disaccharide units that can be variably sulfated and carboxylated along their GAG chain length. These ionizable carboxyl and sulfate groups on GAGs create charged interactive motifs that convey cell regulatory properties important in tissue homeostasis and the maintenance of optimal tissue function. GAGs participate in a number of essential physiological processes including coagulation‐fibrinolysis, matrix assembly and stabilization, immune regulation, and the complement system. The high fixed charge density and the counter‐ions of GAGs is central to their role in the hydration of various connective tissues within the body. Charge transfer properties of GAGs make them amenable to electro‐stimulation and offers a potential mechanism for promoting or enhancing cellular tissue repair processes. This review is undertaken to illustrate these properties and to gain a better understanding of how these processes might be manipulated through electro‐stimulation to help improve tissue repair and the recovery of normal function in traumatized tissues. Weight‐bearing and tension‐bearing, collagen‐rich, avascular tissues have intrinsically poor repair properties and represent difficult clinical challenges. Electro‐stimulation represents a novel approach with significant potential in the stimulation of repair in these most intransigent of tissues