Skin is the body's biggest organ, protecting against chemicals, biological agents, and mechanical effects. Skin injuries suffered by millions of people every year occur due to reasons such as accidents, surgeries, burns, superficial cuts, and traumas. In addition to serious injuries, certain conditions, such as diabetes and vascular diseases, interfere with wound healing and require a longer process [1,2]. Although various approaches have been developed to heal wounds, complete wound healing is a long process and creates a physiological and financial burden. Accelerated wound healing is valuable not just in everyday situations but also in critical scenarios such as wartime and natural disasters, where the swift return to regular activities proves advantageous for individuals and the community [3,4].

The electrical conductivity of the skin, which varies between 0.26 S/m and 1 × 10−5 S/m, has an important role in the complex wound healing process consisting of hemostasis, inflammation, proliferation, and remodeling stages [5]. It is known that the endogenous electric field has a positive effect on wound healing. Although biochemical factors such as enzymes, growth factors, and cytokines have an active role in the self-healing process of a wound, their effectiveness is limited in the case of large and complex defects [6,7]. The application of electric fields at the site of the wound has been documented to direct the movement and growth of skin cells, particularly epithelial cells and fibroblasts, through the activation of ion channels and subsequent transmission of signals. Therefore, an externally applied EF stimulation to mimic natural electrical current in wounds is an alternative method to accelerate wound healing by increasing cell adhesion, migration, proliferation, and differentiation [8,9]. Electrical stimulation has been extensively employed as a form of physical therapy for expediting soft tissue healing and promoting functional recovery, attributed to the application of electrical stimuli, which helps transduce electrobiological signals. Similarly, commercial electrodes have been developed for wound healing, allowing even 18-month-old chronic wounds to heal completely within 12 weeks [10,11]. However, these commercial electrodes are metallic, bulky, and rigid; therefore, their mechanical compatibility with the skin is very low. In addition, they have side effects such as skin inflammation, epidermal peeling, redness, pain, and decreased patient comfort due to long-term contact with the skin [12,13]. Considering these shortcomings of the available systems and since wounds have different shapes and sizes, flexible, stretchable, soft, and conductive wearable wound dressing systems are desired.

Recently, significant advancements have been pursued in creating wearable bioelectrodes for personalized wound care with mechanical compatibility at the skin-electronic interface [14]. Hydrogels have great potential for developing soft wearable bioelectronic materials due to their compatibility with biological systems, adjustable elasticity, ability to conduct electricity, and mechanical properties resembling human tissue. Thanks to their tissue-mimicking properties, they can reduce shortcomings of the metal electrodes in bioelectronic applications, resulting from the sharp structural differences between living tissue and electronic devices. Thus, the new type of wearable conductive hydrogels can effectively carry electronic signals to the cells in the wound tissue by acting as a membrane at the skin interface and can produce the desired therapeutic effects. In addition, hydrogel wound dressing systems provide a hydrated environment due to their high water content, absorb tissue exudates, and contribute to wound healing by providing air permeability [15,16].

PVA is an artificial polymer known for its biocompatibility, tunable mechanical properties, thermal stability, and biodegradability, making it a suitable material for hydrogel fabrication for biological applications. [17]. PVA is affordable, extensively utilized, and recognized as a biomaterial by the U.S. Food and Drug Administration (FDA). PVA is a hydrophilic polymer and has a tendency for hydrogen bonding due to the abundant hydroxyl groups (-OH) in its structure, which results in PVA hydrogels showing high swelling behavior in aqueous solutions and high physical stability [18,19]. Hydrogels made from PVA can be produced using chemical, physical, or a combination of crosslinking techniques. The type of crosslinker and crosslink density in the hydrogel structure affect the swelling capacity and physicochemical structure [20]. Crosslinkers used in synthesizing chemically crosslinked hydrogels are generally toxic and cause undesirable reactions in the bioactive substances of the hydrogel matrix. Using physical crosslinking methods in the production of PVA-based hydrogels prevents such adverse effects [21].

The freeze-thaw (F/T) physical crosslinking process allows us to obtain PVA hydrogels with a standard, simple, environmentally friendly, and easily scalable method. In the F/T process, when PVA aqueous solutions undergo freezing, the water in the polymer dispersion freezes, and the polymer chains concentrate in the unfrozen liquid areas, similar to phase separation, creating high-concentration regions that interact with each other. The close interactions between these chains facilitate the creation of hydrogen bonds, which serve as crosslinking sites, leading to the development of a physical network structure [22,23]. As F/T cycles continue, molecular chains are incorporated into concentrated binding sites. This physical bonding remains intact during thawing, forming a three-dimensional polymer network that does not degrade [24]. In the F/T process, the number and duration of cycles are critical and usually vary between 3 and 10 cycles [25]. F/T crosslinking offers a variety of desired hydrogel properties such as favorable mechanical strength, good stability at room temperature, and the absence of any radical by-products [26]. PVA-based hydrogels are extensively utilized in numerous biomedical fields, such as controlled drug delivery, artificial organs, and tissue engineering, thanks to their biocompatibility and similar biomechanical properties with natural tissues [27,28].

PVA-based hydrogels have low electrical conductivity, so their conductivity needs to be increased in order to be used in bioelectronic fields [29]. To increase their conductivity, materials such as conductive polymers, carbon-based materials, and metal particles are generally added to the hydrogel structure [30,31]. Additionally, structural stability is very important for stable electrical conductivity. Particles added to the hydrogel structure should not be desorbed or agglomerated [32,33]. Incorporating conductive polymers, recognized for their distinctive electrical features, can increase composite hydrogels’ electrical conductivity while improving characteristics such as roughness, porosity, stability, mechanical strength, and degradability. Conductive polymers are also good in creating interpenetrating polymer networks (IPN) and acting as filler agents [34,35]. Poly (3, 4-ethylenedioxthiophene)/poly (styrene-sulfonate) (PEDOT:PSS) is one of the most commonly used conductive polymers in the production of conductive hydrogel bioelectronics due to its adjustable electrical conductivity, excellent thermal stability, and biocompatibility [36,37]. These conductive hydrogel composites are now emerging as a new class of biomaterials for various bioelectronic and controlled drug delivery applications [38].

Stimuli-responsive controlled drug delivery methods allow us to circumvent some of the disadvantages of conventional drug delivery (e.g. IV, PO, or SC) such as limited bioavailability, high doses, and potential toxicity. Controlling how, when, and where drugs reach tissues can increase drug efficacy and improve patient compliance and quality of life by reducing the frequency of doses, drug concentration, and toxicity [39,40] Recent studies have focused on the development of hydrogel-based drug delivery systems that enable controlled drug release under the influence of electric fields, owing to their dual functionality in wound healing—providing localized electrical stimulation and facilitating remotely controlled, precise, and accurate drug delivery [41,42].

The development of hydrogel-nanoclay composite systems has attracted increasing attention for years, as nanoclays have properties such as large surface area, biocompatibility, and high adsorption capacity [43,44]. Laponite (LAP), a synthetic nanoclay, has a large surface area (about 330 m2 g−1) and interlayer voids with a negative charge [45]. It is known that LAP, which has a high swelling ability in water, exhibits an electrically sensitive electro-rheological behavior. Due to its surface charges, reversible changes in rheological properties are observed within a few milliseconds when exposed to an electric field [46]. Drug release from composite hydrogel systems containing LAP is a complex process affected by the electrostatic interactions formed by LAP with the polymer segments and drug molecules. The electric field affects the drug release rate by changing the electrostatic interactions of LAP with the polymer and the drugs. Thus, the drug release rate can be regulated by changing the applied electric field intensity of such drug carrier composite systems [47,48].

Although the mechanical properties of hydrogel electrodes optimized for electrical conductivity are partially improved, achieving mechanical characteristics comparable to those of human skin is of paramount importance for their practical use as wound dressings. In this regard, recent research has increasingly focused on the fabrication of conductive hydrogels integrated with a supporting layer. Such composite systems not only enhance the mechanical performance but also provide a protective barrier between the hydrogel electrode and the external environment, thereby preventing dehydration of the hydrogel during application [49,50]. Natural Rubber Latex (NRL), owing to its skin-like elasticity and flexibility [51], biocompatibility, low cytotoxicity, intrinsic bioactivity in accelerating wound healing, low cost, and ease of processing, presents significant potential as a support material in wound healing applications [[52], [53], [54]].

Here, we developed a PVA/PEDOT:PSS/LAP hydrogel electrode with dual effects capable of electric field-sensitive drug delivery and exogenous EF for wound healing applications (Fig. 1). This electrically conductive hydrogel, which has desirable properties such as mechanical flexibility, stretchability, biocompatibility, and electroactivity, was designed by a simple and facile F/T crosslinking method on the surface of NRL patches. NRL was used as a main support substrate in this study due to its mechanical flexibility and inexpensive nature, and its suitable properties in the wound healing process when used as a physical barrier [53,54]. Tannic acid (TA) was used to provide stabilization between the conductive hydrogel layer and the NRL-based layer. TA is a polyphenolic compound characterized by multiple hydroxyl groups and a high capacity for hydrogen bonding. It is capable of interacting with a variety of polymers through non-covalent, ionic, hydrophobic, and hydrogen bonding interactions. Additionally, TA exhibits antibacterial, antimutagenic, antioxidant, and antigenic properties [55,56]. In PVA-based hydrogels designed for wound dressing applications, TA functions dually as a cross-linking agent and a therapeutic component [57]. Unlike conventional single-layer hydrogel electrodes, this bilayer-designed e-patch system aims to achieve long-term, stable, and effective wound healing by combining the enhanced structural stability and user comfort provided by the NRL-PVA support layer with stable electrical conductivity resulting from preserved hydrogel moisture content, a moist wound environment, and the advantages of patternability. The bioinspired, 3D crosslinked, multifunctional e-Patch system has a stable structure that aids in the performance of electrical stimulation and therapeutic properties in wound healing. The high comfort, micropattern printability, low-cost production process, high moisture content, biocompatibility, and stability features of the developed e-Patch system present an innovative solution to addressing challenges in bioelectricity and personalized wound care.