11.2.5 Electrical stimulation wound dressings
As known，a transepithelial/endothelial potential exists in the organism.When the tissue is damaged，the potential will change，thereby generating a stable and constant directcurrent（DC）electric field，i.e.，the endogenous electric field.Studies have found that the current at the edge of the wound is significantly greater than that at the center of the wound，and the current changes as the wound heals.The internal electrical signal generated by the electric field plays an important role in the healing process of the skin wound.Therefore，by applying an external electric field locally to the wound，it is possible to modify and enhance endogenous bioelectric signals and guide and regulate the distribution，migration，proliferation，and differentiation of fibroblasts，neuronal cells，and endothelial cells，thereby accelerating the orientation of skin tissue repair.Recently，electrical stimulation（ES）therapy at the wound site has been used as an important clinical strategy in the field of tissue repair by reducing wound edema and inflammation，increasing blood microcirculation，and accelerating wound closure.
Wound repair and tissue regeneration are complex processes involving many physiological signals.Therefore，it is possible to use new types of wound dressings with effective biological activity and physiological signal response to accelerating wound healing.At present，researches about ES hydrogel wound dressings are mainly focused on the preparation of conductive hydrogel electrodes and their applications in wound healing.For example，Lu et al.prepared a rGO-CS/SF hydrogel based on PDA，rGO，chitosan（CS），and silk fibroin（SF）.The obtained hydrogel showed good mechanical strength，electrical activity，and anti-oxidizing capability.The composite hydrogels were used as an ES wound dressing.In vitro studies have shown that the electroactive rGO-CS/SF hydrogel can respond to electrical signals and promote cell behavior，and it can also reduce cell oxidation by removing excess reactive oxygen species（ROS）.Studies in the full-thickness skin defect model in vivo showed that it could effectively promote wound healing.
Similarly，Wang et al.prepared a conductive polyHEMA/polypyrrole（PPY）composite hydrogel（Figure 11-8）.When this polyHEMA/PPY hydrogel was used to electrically stimulate diabetic rats，the wound healing was much faster than that achieved by the ES strategy based on commercially available electrodes.(https://www.daowen.com)
In addition，antibacterial properties and mechanical properties should also be considered when designing a conductive hydrogel.Yang et al.developed injectable，biocompatible，selfhealing，and conductive hydrogels（PPGS）based on poly（3，4-ethylenedioxythiophene），poly（styrene sulfonate），and guar cement for various wounds.The results showed that PPGS had great potential in the fields of tissue engineering and biomedicine.Lin et al.obtained conductive hydrogels（i.e.，PDA@AgNPs/CPHs）by using PDA-modified silver NPs（PDA@AgNPs），polyaniline，and poly（vinyl alcohol），which exhibited extensive antibacterial activity against gram-negative bacteria and gram-positive bacteria and could monitor the large-scale movement of the human body in real-time.In addition，PDA@AgNPs/CPHs have a significant therapeutic effect on diabetic foot wounds by promoting angiogenesis，accelerating collagen deposition，inhibiting bacterial growth，and controlling wound infections.
In addition，the use of ES therapy in clinical operations is often restricted by bulky equipment，and it is difficult to achieve real-time treatment.There is an urgent need for wearable and point-of-care equipment that can generate an electric field at the wound site for skin wound healing.Therefore，self-powered devices such as enzyme biofuel cells and nanogenerators have also attracted growing attention，which is small in size and can produce ES without the need for a commercial power source.For example，Nishizawa et al.used flexible enzyme electrodes and stretchable hydrogels to prepare a stretchable bio-electric paste with a built-in enzyme biofuel cell，which generated ionic current on the skin surface through an enzyme electrochemical reaction.Animal experiment results showed that the ion current of electrospun fibers can promote wounds to heal faster and smoother.Zhang et al.developed a hybrid skin patch with a self-adhesive hydrogel and piezoelectric nanogenerator（HPSP，Figure 11-9），which consists of a mussel-like adhered hydrogel matrix and oriented PVDF nanofibers as piezoelectric nanogenerators.The HPSP has Young's modulus similar to that of the skin.It can self-adhere to the wound site，and locally generate a voltage caused by motions.As a wearable real-time ES device，the patch greatly accelerates the healing process and shortens the closure time of full-thickness skin defects by about 1/3.