Stretchable wireless optoelectronic synergistic patches for effective wound healing

Skin wounds from acute injuries and chronic diseases affect over 305 million people worldwide and create a substantial healthcare burden. Current pharmacological therapies can accelerate closure but have concerns including drug resistance, absorption, immune reactions, and healing disorders. Nonpharmacological therapies such as electrical stimulation (ES) and photomodulation (PM) are FDA-cleared physical strategies that can promote repair, but clinical implementations often require bulky equipment and trained operators, limiting accessibility. ES enhances endogenous electric fields to promote epithelial migration and proliferation, but oxidative stress in wounds impairs repair. PM can improve mitochondrial activity and ATP production to reduce inflammation and oxidative stress. Given the complexity of wound environments, mono-therapy is insufficient; combining multiple physical modalities offers synergistic benefits. The authors aim to develop a noninvasive, stretchable, miniaturized, and wirelessly powered optoelectronic synergistic patch (OESP) integrating ES and PM to improve wound healing efficacy and convenience.

Flexible bioelectronics (FBEs) provide lightweight, deformable platforms for in situ therapy and have shown efficacy in delivering ES or PM for wound repair. ES can augment endogenous electric fields to drive epithelial cell migration, proliferation, and differentiation, but is hindered by oxidative stress. PM, including visible/NIR photobiomodulation, can enhance mitochondrial activity and ATP production, dampen inflammatory mediators, and mitigate persistent oxidative stress, reshaping the wound repair process. Given wound complexity, multi-physical field therapies combining ES and PM have emerged to synergistically improve healing. Prior studies demonstrate improved closure with individual ES or PM approaches, yet integration into a comfortable, stretchable, and wirelessly powered format to enable at-home or bedside use and mechanistic validation remains a development challenge addressed by this work.

Device design and fabrication: The OESP comprises seven layers: outer and inner PDMS encapsulation, a double-layer serpentine PI/Cu wireless receiver circuit separated by a PDMS interlayer, a PDMS-supported circular interdigital ES electrode, and a 620 nm LED PM component, all connected via a micro rectifier (M24LR04E-R, 13.56 MHz ±7 kHz, internal capacitance 27.5 pF). Dimensions are ~20 × 20 × 1.58 mm³. The PI/Cu transmitter and double-layer receiver were laser patterned and impedance-matched to 13.56 MHz (NFC). Fabrication steps included nanosecond laser cutting (~2 W), transfer printing of PI/Cu onto PDMS, double-layer folding using alignment marks, soldering of rectifier/LED/interdigital electrode, and PDMS encapsulation. Geometry: Receiver serpentine linewidth 200 µm, arc angle 120°, radius 300 µm. Interdigital electrode linewidth/spacing 200 µm, 6 rings, ~12 mm diameter. Performance simulations and matching: HFSS simulations varied PDMS interlayer thickness (0.1–1.5 mm) showing resonant frequency increasing with thickness; 1.0 mm (measured ~1.03 mm) selected to target 13.56 MHz. A spiral transmitter (inner radius 30 mm, outer 40 mm) with components (C1=16 pF, C2=82 pF) provided measured S11: resonance 13.76 MHz, return loss −27.19 dB, bandwidth 0.62 MHz (13.45–14.07 MHz). Load dependence: highest Vpp ~6.0 V with a 27 pF load capacitor; output decreased with receiver–transmitter distance. Thermal behavior: Infrared thermography showed stable operation with max/min/mean surface temperatures ~33.52/30.27/32.37 °C. Mechanics and biocompatibility: FEA and uniaxial tensile tests (0–30% strain) showed even strain distribution on serpentine lines; at 30% device strain, local copper strain ~0.3% (<5% failure), indicating robustness. The device tolerated repeated 0–30% stretching. Biocompatibility was assessed by culturing mouse fibroblasts on PDMS-encapsulated OESP vs dish controls for 3 days with fluorescence imaging and CCK8 viability; no cytotoxicity differences were observed. In vivo biosafety: subcutaneous implantation in SD rats showed no vital organ pathology at 2 weeks (H&E). Breathability for wound dressings: Porous PDMS was prepared by a sodium chloride templating method (10 wt% NaCl) and leaching post-cure; resulting water vapor transmission rate (WVTR) 117.1 ± 17.1 g/(m²·h). Animal model and interventions: Six-week-old male Sprague-Dawley rats (n=16; ~180±20 g) were randomized into four groups (n=4/group): OESP (combined ES+PM), ES-only, PM-only (LED 620 nm), and control (PDMS film only). Full-thickness circular dorsal skin wounds (~1 cm diameter) were created under isoflurane anesthesia. Patches were affixed with medical surgical glue. Interventions were continuous over 7 days; wounds were documented every 2 days up to day 8. An open field test assessed behavior/pain; no significant differences vs controls were found. Wound closure rate was calculated as: (Wx − W0)/W0 × 100%, where W is closure area at day x. Histology and molecular assays: On day 8, wound tissues underwent H&E and Masson’s trichrome staining to assess reepithelialization and collagen/matrix remodeling. Immunohistochemistry (IHC) for CD31 quantified microangiogenesis (average optical density, IntDen/Area). Immunofluorescence (IFC) quantified growth factors EGF, TGF-β, and VEGF. ImageJ v1.8.0 with Profile plugin computed IHC/IFC expression. Mechanism in vitro: L929 fibroblasts under H₂O₂-induced oxidative stress were subjected to PM; mitochondrial membrane potential (MMP, Δψm) was assessed using JC-1 staining (green/red ratio) via fluorescence microscopy and flow cytometry to evaluate PM protection against mitochondrial depolarization. Statistical analysis: Group comparisons with significance thresholds noted (e.g., P<0.05). Ethical approvals: Animal protocols approved by University of Electronic Science and Technology of China (1061420210617002).

• Stretchable, wirelessly powered OESP operated robustly under up to 30% tensile strain with even strain distribution; maximum copper strain ~0.3% under 30% device strain, below failure (~5%). Dimensions ~20 × 20 × 1.58 mm³; seamless skin conformability demonstrated.
• Wireless performance: Double-layer serpentine receiver with ~1 mm PDMS interlayer matched to 13.56 MHz; measured S11 resonance at 13.76 MHz with −27.19 dB return loss and 0.62 MHz bandwidth (13.45–14.07 MHz). Peak receiver Vpp ~6.0 V at matched 27 pF load; output decreased with increasing transmitter distance.
• Thermal safety: Stable skin-surface temperatures during operation (avg max 33.52 °C, min 30.27 °C, mean 32.37 °C).
• Biocompatibility: Fibroblast morphology and viability comparable to controls over 3 days (CCK8), and in vivo implantation showed no vital organ damage at 2 weeks. Open field tests indicated no pain/anxiety-like behavior differences vs controls.
• Breathable dressing: Porous PDMS achieved WVTR 117.1 ± 17.1 g/(m²·h), suitable for wound dressing breathability.
• Wound closure efficacy (day 8, mean ± SD, n=4/group): OESP 94.12 ± 3.399% vs ES 81.57 ± 2.381%, PM 79.47 ± 3.073%, Control 65.25 ± 6.782%; OESP significantly outperformed others.
• Histology: OESP group showed complete reepithelialization with a new epidermis closely linked to granulation tissue, abundant orderly collagen deposition, and presence of hair follicles and sebaceous glands, indicating advanced healing. ES and PM showed intermediate healing; controls lacked epidermis and exhibited delayed repair.
• Angiogenesis (IHC CD31, average optical density): OESP 49.7 > PM 31.62 > ES 26.28 > Control 16.45, indicating enhanced microvessel formation with OESP.
• Growth factors (IFC, average fluorescence expression): EGF—OESP 35.19, ES 19.29, PM 21.28, Control 10.35; TGF-β—OESP 28.15, ES 10.19, PM 15.85, Control 4.46; VEGF—OESP 37.92, ES 27.43, PM 25.32, Control 12.22. OESP significantly increased all three factors, with VEGF particularly elevated.
• Mechanism in vitro: PM mitigated H₂O₂-induced mitochondrial depolarization in L929 fibroblasts, lowering JC-1 green/red ratio toward control levels (fluorescence microscopy and flow cytometry), supporting mitochondrial protection, enhanced energy metabolism, and potential ROS reduction.

The study demonstrates that integrating electrical stimulation and photomodulation in a stretchable, wirelessly powered patch produces a synergistic effect on wound healing. ES likely enhances endogenous electric fields to promote epithelial cell migration and proliferation, while PM improves mitochondrial function, ATP production, and reduces oxidative stress, thereby decreasing inflammatory mediators. This combination increased angiogenesis (CD31) and elevated key growth factors (EGF, TGF-β, VEGF), advancing reepithelialization and matrix remodeling. The OESP’s mechanical compliance and wireless operation enable reliable therapy delivery on irregular skin without cumbersome wiring, potentially improving adherence and comfort. In vitro data support a mechanism where PM preserves mitochondrial membrane potential under oxidative stress, reducing ROS and supporting cellular activities essential for repair. Collectively, these findings address the need for noninvasive, effective, and convenient wound therapies, indicating that multi-physical field interventions can outperform monotherapies in a preclinical model.

A stretchable, flexible, and wirelessly powered optoelectronic synergistic patch integrating ES and 620 nm PM was developed and optimized to operate at 13.56 MHz with robust mechanical compliance (~30% strain). In a rat full-thickness wound model, OESP significantly accelerated healing, achieving ~94% closure at 8 days and superior histological regeneration compared with ES-only, PM-only, and control groups. Mechanistic analyses showed enhanced angiogenesis and elevated growth factors (CD31, EGF, TGF-β, VEGF), consistent with accelerated reepithelialization and matrix remodeling. PM protected mitochondrial function under oxidative stress, suggesting reduced ROS and improved cellular energetics as part of the synergistic effect. The wireless, miniaturized, and breathable design supports potential translation to comfortable, precise, and even bedside treatments (e.g., antenna integrated at hospital beds). Future work could include optimization of stimulation parameters and dosing, long-term safety and efficacy studies, expanded animal models and wound types (including infected or chronic wounds), characterization of ES/PM dose-response, power transmission range optimization, and steps toward clinical trials.

The study is preclinical with a small sample size (n=4 per group) and an 8-day observation window, limiting generalizability and long-term safety assessment. Efficacy was demonstrated in healthy rats with acute full-thickness wounds, which may not fully model chronic or infected human wounds. Wireless power output decreased with increasing distance from the transmitter, potentially constraining practical deployment without optimized antenna placement. Detailed ES parameterization (e.g., exact current/voltage waveform at the tissue) was not extensively reported in the provided text, and only a single PM wavelength (620 nm) was evaluated.