Flexible and Scalable Dry Conductive Elastomeric Nanocomposites for Surface Stimulation Applications

Abstract

Objective:

The study describes the development and testing of a dry surface stimulation flexible electrode (herein referred to as Flexatrode), a low-cost, flexible, and scalable elastomeric nanocomposite using carbon black (CB) and polydimethylsiloxane (PDMS).

Methods:

Flexatrodes composed of CB and PDMS were developed and tested for mechanical and functional stability up to 7 days. Uniform CB distribution was achieved by optimizing the dispersion process using toluene and methyl-terminated PDMS. Electromechanical testing in the through thickness directions over a long-term duration demonstrated stability of Flexatrode. Thermal stability of Flexatrode for up to a week was tested and validated, thus mitigating concerns of heat generation and deleterious skin reactions such as vasodilation or erythema.

Results:

25 wt.% CB was determined to be the optimal concentration. Electrical and thermal stability were demonstrated in the through thickness direction.

Conclusion:

Flexatrode provides stable electrical properties combined with high flexibility and elasticity. Electrotherapy treated chronic wounds were 81.9% smaller than baseline at day 10. Wounds that received an inactive device (device without any electrical stimulation) were 58.1% smaller than baseline and wounds that received standard of care treatment were 62.2% smaller than baseline.

Significance:

The increasing need for wearable bioelectronics requiring long-term monitoring/treatment has highlighted the limitations of sustained use of gel-based electrodes. These can include skin irritation, bacterial overgrowth at the electrode site, gel dehydration over time, and signal degradation due to eccrine sweat formation. Flexatrode provides stable performance in a nanocomposite with scalable fabrication, thus providing a promising platform technology for wearable bioelectronics.

I. Introduction

The integration of miniaturized surface mount electronic components on flexible substrates has ushered in a new era of bioelectronic wearable devices that can safely adhere to the skin for extended periods of time. The development of flexible, and biocompatible electrodes is recognized as essential for these applications [1], [2], [3], [4]. Current electrode technologies used for measuring biosignals are generally in pre-defined form factors that cannot readily be integrated with flexible substrates to form integrated devices. Dehydration or contamination of the conductive gels on the electrodes due to long-term wear, build-up of sweat and bacterial growth underneath the electrode adversely affects the signal-to-noise ratio of the measured biosignals and increase overall impedance, thereby hindering clinical utility. Adhesives used to adhere electrodes to the skin have also been found to cause erythema [5]. Thus, there remains an unmet clinical and engineering need to develop scalable electrode technologies without compromising the essential electrical and biological functional properties when placed directly on the skin.

Flexible bioelectronic devices leveraging host substrate materials such as polydimethyl siloxane (PDMS) for medium- or long-term wearable applications require integrated dry conductive elastomeric contact pads to serve as a “bridge” between metallic electrodes on the flexible substrate with the skin. Mechanical flexibility is crucial for devices in contact with the skin to conform to the body topography and to minimize discomfort without impeding electrical contact. PDMS-based nanocomposites utilizing conductive materials such as silver nanowires [6], graphene [7], carbon nanotubes [8], and carbon black (CB) [9], [10], [11], [12], [13] as fillers have been explored recently. The scalability, low-cost, and proven biocompatibility when tested in human primary epidermal keratinocytes [10], [11], [12] makes CB an attractive nanomaterial for flexible electrodes [14]. Carbon black consists of spherical carbon particles which are fused together in aggregates [15]. The primary obstacle to electron flow in the CB matrix is located at the interface between the particles of the various CB aggregates [15], [16]. Kelly et al. found that the maximum weight percentage of CB, that can be added to form a nanocomposite without adversely affecting the flexibility of the PDMS, is ~25 wt% [17].

Research into the inclusion of CB in elastomers such as PDMS has primarily focused on either improving fabrication methodologies (e.g., screen printing [18]) and/or using lower percentages of CB between 10–15% to maintain the necessary flexibility needed for wearable bioelectronics, specifically for strain gauges [14], [19] or for physiological monitoring [11], [12], [20]. However, the electrical resistances of these materials are too high for clinical applications using surface electrical stimulation [21], [22]. Despite advancements in the development of various elastomeric nanocomposites, there remains a gap in longitudinal benchtop studies towards evaluating the bio-electrical performance of these materials in clinically relevant environments. Furthermore, the majority of reported testing has evaluated the electrical properties of CB-based elastomeric nanocomposites in the lateral direction but not in the through thickness direction. We hypothesize that studying the resistance profiles in the through thickness direction will provide data on CB agglomeration and dispersion within the host elastomer as well as the potential for use as electrode material for surface stimulation and recording.

Towards addressing this knowledge gap, the current study assessed the mechanical and electrical properties of the Flexatrode CB-PDMS elastomeric nanocomposite, specifically for surface electrode applications. Flexatrode electro-mechanical and adhesive properties were assessed in the through thickness direction towards establishing clinical utility in wearable electroceutical devices. We demonstrate the efficacy of Flexatrode (when integrated into a flexible smart bandage device) as a conductive elastomeric nanocomposite for the delivery of an electroceutical therapy for chronic wound healing. Thus, this work demonstrates the translational pathway of a flexible elastomeric nanocomposite for surface stimulation applications requiring a low impedance in the through thickness direction and stability in both dry and hydrated (wet) environments.

II. Materials and Methods

A. Materials

All PDMS components were purchased from Dow Corning (Midland, MI, USA) and used with carbon black from Cabot (CAS#1333-86-4; Boston, MA, USA). All chemicals, including toluene, were high-performance liquid chromatography (HPLC) grades from Sigma-Aldrich (St. Louis, MO, USA) and Fisher Scientific (Waltham, MA, USA). SPI Flash-Dry Silver epoxy was from Structure Probe, Inc. (West Chester, PA, USA). Carbon wire glue was brought from Anders Products (Andover, MA, USA). The AWG30 size hook-up wires were from Remington Industry (Chicago, IL, USA). Impedance measurements were obtained using a GW-INSTEK LCR-821 meter (New Taipei City, Taiwan). Substrates were copper-clad polyimide (Cu-PI) (Pyralux LF8530R DuPont) consisting of 75 μm-thick polyimide and 18 μm-thick copper. 3M Electrically Conductive Adhesive Transfer Tape 9713 was used to adhere Flexatrodes to Cu-PI substrates. A commercially available medical-grade silicone acrylate adhesive (2477P, 3M Inc.) bonded the Flexatrode device to the skin for adhesion studies. Sodium carbonate (R71850004A; MG Chemicals) and sodium persulfate (4101; MG Chemicals) were used as received as developer’s solution and copper etchant.

B. Flexatrode Fabrication

Sylgard-184 was used in the CB-PDMS layer because of its flexibility and long-term mechanical robustness. Flexatrode samples were fabricated using a procedure previously described in [14], [23] (Fig. 1). CB particles were prepared by grinding carbon granules in a ceramic mortar and sieving the resulting powder to 0.1 mm. Next, the appropriate amount of filtered powder to achieve the desired carbon-black concentration in the PDMS composite was dispensed into a clean beaker. Toluene was added to the CB, and the beaker was sonicated for 30 min (Qsonica Q500 probe, 500 W, 20 kHz, 30% duty cycle) to ensure thorough mixing and dispersion of the CB particles. Next, the PDMS elastomer (base and curing agent) were added to a clean beaker along with toluene and mixed for 30 min. The CB-PDMS-toluene mixture was poured into a polyethylene mold and cured at 80 °C for 2 hours.

Fig. 1.

Process-flow of Flexatrode fabrication.

The resulting Flexatrode samples (length: 4 cm, width: 1 cm, thickness: 300 μm) were peeled from the mold and used for testing.

C. Cyclic Testing

The mechanical stability of the CB-PDMS under periodic loading was evaluated using a cyclic tensile test performed on a 25 wt% CB sample. The test structure was subjected to cyclic loading over a strain range of 0 to 2.5% at 5 Hz for 50 cycles.

D. Electrical Testing

Flexatrode samples were wired using flash-dry silver epoxy (SPI Flash-Dry Silver) to make pads (surface area = 0.25 cm²) and then connected with AWG-20 jumper wires, held in place using carbon wire glue. After drying at room temperature for 24 hours, a further application of silver epoxy was used to enhance wire connection rigidity. Electrical contacts to the secured wires on each sample were made using standard probes in the lateral and through thickness direction (Supplementary Figs. 1 and 3, respectively). For resistance testing, 3 rectangular samples (40 mm in length, 10 mm in width and 0.3 mm in thickness) were fabricated from each CB concentration set. Standard, two-point, current-voltage (I-V) measurements were made on each sample using a DC power supply (Keysight E3631A) and a picoammeter (Keithley 6485). Electrical measurements were characterized in the through thickness direction, to investigate the relationship between CB concentration and resistance. Each sample was secured to a glass slide to ensure that there was no stretching or flexing during I-V sweeps. The voltage was swept from 0 to 3.5 V in 0.1 V steps. The resistance was calculated from a linear fit of the I-V data. For each sample, 50 I-V loops were performed, and an average resistance was calculated in each sweep.

E. Impedance Testing

Flexatrode (length 4 cm, width 1 cm, and thickness 0.3 mm) impedance was evaluated over a frequency range from 12 Hz to 100 kHz using an LCR meter (Instek LCR-821). A hand-held multimeter was used to measure the resistance at 1 Hz. Axelgaard-735 (AG-735) (length 4 cm, width 1 cm, and thickness 0.2 mm) hydrogel electrode used in prior published work as a surface stimulation electrode for wound healing was used as a control [24], [25]. Experiments were run over 7 days, and data were collected at Day 0, 1, and 7 in both dry and hydrated environments, specifically phosphate buffer saline (PBS) solution, pH 7.4. Long term testing for 7 days was selected because epidermal-based wearable devices used for physiological monitoring are typically worn for no longer than 7 days. All experiments were run in triplicate.

F. Absorption Testing

Flexatrode and AG-735 electrodes were immersed in PBS solution, pH 7.4 and weighed at hourly increments for the first 5 hours followed by 24-hour increments for up to 7 days. All experiments were run in triplicate.

G. Pre-Clinical Assessment

The efficacy of Flexatrode as a surface stimulation electrode for the delivery of electroceutical therapy was evaluated in a pre-clinical study (Institutional Animal Care and Use Committee (IACUC) (Louis Stokes Cleveland Veterans Affairs #16–071-SW-16–009 and Case Western Reserve University (CWRU) #: 2016–0331, project approval date: 01/18/17). Six full-thickness excisional wounds (6 cm diameter, 2.5 −3 mm deep) were created bilaterally over the paraspinal region in each animal. Intra-operative anesthesia was maintained by isoflurane. The back of the animal was clipped and then wiped liberally with 4% chlorohexidine. A template was used to mark the locations of wounds to be created. Full-thickness wounds (6 cm diameter) were excised bilaterally over the paraspinal/flank region at a distance of 4 cm. Each pig served as its own control with two wounds receiving an active device (wearable electroceutical bandage with electrical stimulation), two wounds receiving inactive devices (wearable electroceutical bandage without electrical stimulation), and two wounds receiving standard of care treatment (commercial wound dressing). In order to create an ischemic wound, a sterile double-flanged silicon block was sutured into each wound for 14 days. The flanges were 9 cm in diameter and 0.5 cm high. The central core of the wound insert block was 6 cm in diameter and 1 cm high. Each wound was covered with a Tegaderm dressing. The animals were wrapped in an elastic bandage (VetRap 3M Health Care, St Paul, MN) to prevent animals interfering with the system. The pigs were covered with a protective body jacket (Goat Tube, Sullivan Supplies, Houston, TX) to prevent environmental contamination. The animals were awakened from general anesthesia, given post-operative analgesia, and placed in single-occupancy pens. They were maintained with standard laboratory feed and water ad libitum. Following the 14-day period, the wound plugs were removed and all wounds were inoculated with 0.5 McFarland solution of GFP labeled p. aeruginosa as used in our preliminary work. Inoculation with p. aeruginosa facilitated the formation of a biofilm layer on the wound. Active and inactive devices along with standard of care wound dressings were applied and changed at pre-determined Biopsy Timepoint Days (BTDs 0, 1, 3, 7, 10, 14, 17, 21, 28, 35, and 42).

The substrate was discarded, and the electronics module was replaced at each timepoint. Stimulation frequency for the active devices was set at 20 Hz with a current density of 5.3 μA/cm², an interpulse interval of 50 ms, a pulse width of 110 μs, a duty cycle of 10%, and a current amplitude of 16 mA [24], [25]. All pigs were sacrificed at the end of the stimulation period. Euthanasia was carried out by administration of 6–10 mg/kg IM Telazol for sedation and 100 mg/kg IV Euthasol. This method followed the recommendations of the AVMA Panel on Euthanasia and has been approved for use by our group in a pig study previously active at CWRU [21], [25].

III. Results and Discussion

The electrical, mechanical, and surface properties of Flexatrode samples were evaluated by benchtop testing. A representative plot of an I-V sweep for composite samples from each of the CB concentration sets shows that the samples exhibit ohmic behavior (Fig. 2(a)). Electrode conductivity is predicated on the interaction and conductive pathways formed between the CB particles. Our data suggests that at lower CB concentrations such as 10%, the statistical likelihood of conductive paths formed in the composite is lessened, thereby causing greater variance when near threshold [14]. We also found significantly improved electrical characteristics of the nanocomposite when the CB concentration approached 25 wt%. However, CB concentrations beyond 25 wt% did not improve the electrical conductivity or the mechanical stretchability of the nanocomposite. Indeed, prior work has found that CB concentrations greater than 25 wt% led to adverse mechanical properties for the nanocomposite, specifically a change from an elastomeric composition to a brittle state [17]. Resistivity, which was calculated from the resistance measured in Supplementary Fig. 2, decreased with increased CB concentrations (Fig. 2(b)).

Fig. 2.

Flexatrode samples at varied CB concentrations. (a) Current-voltage sweeps at varied CB concentrations. Data represents mean I-V curves for three samples. (b) Calculated resistivity at varied CB concentrations. (c) Water contact angle of flexatrode samples. Data presented as mean ± std. dev of three samples per CB concentration set.

Water contact angle was evaluated to quantify changes in the hydrophobicity of the PDMS surface based on varied CB concentrations (Fig. 2(c)). Increased hydrophobicity was observed from 0% to 25 wt% CB. This suggests that the addition of CB had a minor impact on the surface properties of the native PDMS substrate and that the surface chemistry of the Flexatrode is unaffected changes in CB concentration.

A composite consisting of 25 wt% CB-PDMS was selected for further testing based on its superior electrical performance and surface properties (Table I).

TABLE I.

Effect of CB Concentrations on Mechanical and Electrical Properties of Flexatrode

CB (%)	Mean Current Amplitude (mA)	Resistivity (Ω-cm)	Contact Angle (°)
0	N/A	N/A	100.1 ± 1.90°
10	0.0530	2242.43 ± 144	99.63 ± 1.50°
14	0.770	87.45 ± 5.33	101.4 ± 1.80°
18	1.93	36.38 ± 1.47	102.6 ± 2.90°
25	3.99	18.08 ± 0.46	103.8 ± 2.00°

Data presented as n = 3; mean ± std. deviation.

Mechanical cyclic testing of the Flexatrode over 2.5% strain at a frequency of 5 Hz demonstrated consistent cyclic stress of ~225 kPa over 50 cycles (Fig. 3(a)). The lack of hysteresis indicated that the Flexatrode is mechanically stable under dynamic loading over a period of 5 hours. One such application where the use of Flexatrode as a surface stimulation electrode could experience cyclic straining is at-home electroceutical therapy following arthroscopic surgery (e.g., Anterior Cruciate Ligament reconstruction) [26]. In this case, Flexatrode would be placed over the knee and electrical stimulation would be delivered from a power source through Flexatrode to the skin to facilitate and improve vascularization and osseointegration of the neo-ligament at the surgical site. The therapy lasts about one hour per day. Thus, benchtop testing to assess mechanical stability was chosen for a long-term duration (e.g., 5 hours) to factor in such therapy times. An increase in cyclic stress of ~125 kPa was noted in the Flexatrode sample relative to 100% PDMS, demonstrating the CB impact. The uniform Flexatrode cyclic stress behavior also demonstrated CB stability. Flexatrode electrical stability was confirmed at room temperature (17 °C) and physiological temperature (40 °C) (Fig. 3(b)).

Fig. 3.

Mechanical and I–V properties of flexatrode at 25 wt% CB concentration. (a) Cyclic stress of Flexatrode response under repeated cyclic loading; (b) I–V profiles of Flexatrode at room temperature (17 °C) and physiological temperature (40 °C).

Flexatrode electrical actuation was evaluated over 3000 loops (5 hours) in the through thickness direction in both a dry and hydrated environment (Fig. 4). Testing the Flexatrode in a hydrated environment (Phosphate Buffer Saline (PBS), pH 7.4) is representative of interacting with bodily fluids such as eccrine sweat or wound exudate. Hydrated samples were covered to prevent evaporation during the testing process. In the through thickness direction for the dry Flexatrode, there was an initial decrease of ~21 Ω over the first 30 minutes after which resistance remained constant around 447 Ω. A similar trend was noted when studying the hydrated sample in the thickness direction, albeit a larger drop during the transient period with the resistance stabilizing at ~468 Ω. We hypothesize that the decrease in resistance during the transient period (~30 minutes) was possibly attributed to the evaporation of the PBS solution. Results confirm that interaction between fluid and the electrode surface does not adversely affect the long-term Flexatrode performance. The homogeneity in resistance profiles over the 5-hour period suggest that the bulk properties of the Flexatrode remain unchanged thereby confirming the stability of the CB nanoparticles within the PDMS matrix.

Fig. 4.

Electrical resistance of flexatrode when exposed in a dry and hydrated (PBS solution) environment over a 5-hour period during continuous cycling in the through thickness direction.

While prior published work has assessed the signal quality of CB-PDMS electrodes immersed in a hydrated environment for underwater physiological monitoring applications over a one-week duration [10], [11], [12], this study presents the first example elucidating the long-term performance of a CB-based elastomeric nanocomposite for surface stimulation applications, particularly in the through thickness direction. This data is particularly useful as it demonstrates that during direct current (DC)-based stimulation, the electrical stability of the nanocomposite in the bulk regime remains relatively unchanged. This would have significant clinical implications from a dermatological standpoint as discussed next.

Approximately 10% of individuals suffer from erythema (extreme redness and rashes) from gel-based electrodes [5]. This can be attributed to the adhesive and/or heat generation during electrode cycling during electroceutical therapy [27]. Furthermore, with the recent hype and adoption of wearable Continuous Glucose Monitors (CGMs), the need to develop electrodes that facilitate delivery of an electrical stimulus for excretion of bodily fluids such as eccrine sweat for glucose monitoring without causing iatrogenic skin injuries in patients remains an unmet clinical need. The electrical stability of Flexatrode over a 50-hour period during continuous cycling of current at an average of 10 mA was therefore evaluated (Fig. 5(a)). It was found that the electrical response was stable with a temperature change of only 0.1 °C, measured using a hand-held infrared thermography camera (Fig. 5(b)). Our data suggests that Flexatrode may be appropriate for applications requiring either continuous or pulsed delivery of an electrical stimulus.

Fig. 5.

Long-term electrical stability of Flexatrode over 50 hours during continuous cycling. (a) Resistance versus time (hours) in dry lateral direction, (b) heat output based on changes in temperature at hour 0 and hour 50.

A thermal stability experiment was carried out to observe the Flexatrode response to increasing temperature over a range from 22 to 51 °C (Fig. 6). Resistance was measured in the through thickness direction against a temperature sweep from 22 to 51 °C. The resistance of the Flexatrode samples over the temperature range increased by 12.9% in the through thickness direction (322.48 ± 74.6 Ω to 364.11 ± 81.4 Ω). Over a physiologically relevant window between 35 °C to 41 °C, the resistance of the Flexatrode samples increased by 7.8% (322.48 ± 74.6 Ω to 347.51 ± 77.7 Ω). Thus, the data confirms the stability of the composite over this temperature range. The stability in resistance observed across a physiological range suggests the applicability of Flexatrode for use as a surface electrode.

Fig. 6.

Evaluating the resistance versus temperature in the through thickness direction.

Flexatrode performance when stretched was evaluated using the normalized change in resistance (ΔR/R_o) at 2.5%, 5%, and 10% strain (Fig. 7) [28]. Trung et al. reviewed the applications of stretchable physical sensors for human performance [28]. The authors concluded the required stretchability limit was <2% and <20% for applications on the face and hand, respectively. Thus, a range of 1 to 10% strain was carried out for our benchtop testing. Normalized change in resistance (ΔR/R_o) increased with strain, with a greater increase in the lateral direction. ΔR/R_o increased with increasing strain (0.106 ± 0.082 at 2.5%, 0.241 ± 0.12 at 5%, and 0.619 ± 0.097 at 10%). Results demonstrate that ΔR/R_o in the through thickness direction at maximum strain was ~0.55. Thus, results demonstrate the mechanical stability of Flexatrode in the through thickness direction, suggesting that the intercalation of the CB within the PDMS bulk is stable at 10% strain. Furthermore, despite the increased stiffness due to the presence of the filler, the use of PDMS as a host substrate platform provides flexibility to the Flexatrode.

Fig. 7.

Evaluating the change in resistance based on change in displacement at 2.5%, 5%, and 10% strain.

Flexatrode impedance was evaluated against AG-735 over a frequency range of 1 Hz-100 kHz. (Fig. 8). AG-735 was selected based on its prior use as a hydrogel electrode for surface stimulation applications [24], [25]. Testing was performed in the through thickness direction in both a dry and hydrated environment. As expected with a hydrogel electrode, the presence of moisture at Day 1 and 7 decreased in impedance of AG-735, owing to the intercalation of the aqueous solution. Biomedical applications utilizing surface stimulation electrodes such as for wound healing have been shown to be efficacious when delivering stimulation at frequencies (but not limited to) 20 Hz [21], [29], [30]. The homogeneity in impedance was observed across a broad range thereby demonstrating the utility of the Flexatrode for biomedical applications warranting delivery of an electrical stimulus. Impedance stability over 7 days demonstrated the stability in CB nanoparticle intercalation within the PDMS bulk. Furthermore, the presence of moisture did not alter Flexatrode impedance, thus confirming our contact angle studies indicating the stable hydrophobicity. Over a 7-day span at 20 Hz, the impedance of the Flexatrode electrode was markedly lower than that of AG-735 (Table II).

Fig. 8.

Through thickness impedance of the flexatrode compared to a commercial hydrogel electrode over 7 days in a dry and hydrated environment. (a) Day 0 dry. (b) Day 1 hydrated. (c) Day 7 hydrated.

TABLE II.

Comparative Through Thickness Impedance of Flexatrode and AG-735

Electrode	Day 0	Day 1	Day 7
Flexatrode	180.7 Ω	356 Ω	264 Ω
AG-735	15.5 kΩ	3.74 kΩ	3.8 kΩ
Percent Difference (%)	98.8%	90.4%	93.1%

The absorption capabilities of Flexatrode were compared against AG-735 over 7 days (Fig. 9). AG-735 demonstrated a ~600% mass increase over the initial 24-hour period compared to ~12% increase for Flexatrode. At day 7, AG-735 demonstrated a ~500% mass increase while Flexatrode demonstrated ~15% increase.

Fig. 9.

Absorption capabilities of flexatrode compared to AG-735 over 7 days. n = 6 samples; mean ± std. dev reported.

Systems using disposable surface electrodes require wound dressings to be removed so the electrodes can be placed at each treatment session and removed post-treatment. This introduces the potential for heterogeneity in treatment delivery due to errors in repeatability of electrode placement and increases infection risk due to repeated wound exposure. Appropriate and repeated delivery of electrotherapy to the wound bed has the potential to limit incident planktonic and polymicrobial colonization and accelerate healing. Integration of Flexatrode onto a self-contained wearable electroceutical device would mitigate such heterogeneity in treatment delivery. An example of such a device is presented herein (Fig. 10). The device was designed to meet the wound healing timeframe by tailoring the size of the bandages to that observed during wound reepithelization. Three bandage sizes were created: 6 cm (8.7 cm × 9 cm), 4 cm (8.7 cm × 7 cm), and 2 cm (8.7 cm × 5 cm).

Fig. 10.

Wearable electroceutical device with integrated flexatrodes for electroceutical therapy. (a) Electronics interfacing side of the device. (b) Skin-interfacing side of the device. (c) Application of the active device over the wound at a specified timepoint. Multilayer substrate integrates flexatrodes, AFTIDerm and temperature sensors.

The electronics (Fig. 10(a)) and skin-interfacing sides (Fig. 10(b)) are shown. Flexatrode served as a conductive and soft-bioelectronics between the device and skin to prevent bio-fouling on the copper electrodes which were microfabricated on a flexible copper-clad polyimide substrate. The inexpensive, and biocompatible device, also includes an absorbent, transparent, central region (AFTIDerm [[31]]) which enables visualization of the wound bed without removing the entire device. The device substrate was adhered to the skin of the pig using biocompatible adhesives and left in place until the following time point (Fig. 10(c)).

Bright field imaging from one pig over a 28-day period shows the re-epithelization of the wounds receiving the electroceutical therapy compared to wounds that received inactive devices or standard of care treatment (Fig. 11(a)). Results demonstrated that electrotherapy treated chronic wounds were 81.9% smaller than baseline at Day 10. Wounds that received an inactive device, were 58.1% smaller than baseline and wounds that received standard of care treatment were 62.2% smaller than baseline (Fig. 11(b), (c)). By Day 28, the integration of Flexatrode with a wearable electroceutical bandage increased the rate of wound healing and thus decreased the full healing time.

Fig. 11.

Wearable electroceutical device with integrated flexatrodes. (a) Images comparing change in re-epithelization of wounds based on wounds receiving the active device, inactive device, or standard of care treatment (b) wound area (cm²) versus time (days) (c) wound closure (%) versus time (days). n = 10 wounds per treatment group (five pigs total).

IV. Conclusion

Flexatrodes composed of CB and PDMS have been developed and tested for mechanical and functional stability up to 7 days of constant use. The fabrication methodology facilitates adapting Flexatrode geometry to match the clinical specifications required for wearable electroceutical applications. A composite consisting of 25 wt% CB-PDMS was determined to have the optimal CB concentration based on its superior electrical and surface properties. Flexatrode did not demonstrate mechanical fatigue when undergoing cyclic stress over 6 hours together with electrical stability when tested at a physiologically relevant temperature of 40 °C. The thermal stability of the Flexatrode over a 50-hour period was confirmed. The maximum Flexatrode stretchability without significant hysteresis, was between 5–10%, which is well-suited for some epidermal electronic applications. Impedance homogeneity across a wide frequency range demonstrated Flexatrode electrical stability. This is particularly useful for biomedical applications utilizing a surface electrode for electrical stimulation. Flexatrode demonstrated minimal mass increase over 7 days in a hydrated environment. The stable mechanical, electrical, and thermal properties suggest the translational potential for applications in biomedical engineering necessitating use of a dry electrode as a standalone modality for human health and performance or for integration into a wearable device. Pre-clinical validation of Flexatrode as a surface stimulation electrode in a porcine chronic wound model demonstrates its use for applications necessitating the delivery of an electroceutical therapy such as wound healing.