Accelerated wound healing with an ionic patch assisted by a triboelectric nanogenerator

Abstract Electrical stimulation therapy has recently been suggested as a therapeutic modality to accelerate wound healing. Despite advancements in the development of flexible electronic devices for rapid wound recovery, current systems, which are fabricated from various metals, have mechanical discontinuities that have not been fully resolved, making them unsuitable for wearable applications. Here, we introduce a wearable ionic triboelectric nanogenerator (iTENG) patch, composed of a fully stretchable gel-based platform comprising a TENG, wire, and patch that harvests biophysical energy and delivers electric potential to an impaired tissue. Ionically conductive and stretchable organogel fibers in an elastomeric microtubular structure act as both a stretchable wire and a wearable generator as they are woven like fabric. The elastomeric film-encapsulated ionic patch is multifunctional, serving as both a wound dressing and an electrode. It provides a uniform and symmetrical electric field directly to a wound bed. The electric field generated by an iTENG was shown to accelerate in vitro cell migration, proliferation, and secretion of angiogenic growth factors in studies on both normal human dermal fibroblasts and dermal fibroblasts from diabetes mellitus patients. Rapid wound closure by electrical stimulation using iTENG patches in in vivo animal models has also been verified.

[1]  Seok Hee Han,et al.  A Stretchable Ionic Diode from Copolyelectrolyte Hydrogels with Methacrylated Polysaccharides , 2018, Advanced Functional Materials.

[2]  Ying Chen,et al.  A convenient method for quantifying collagen fibers in atherosclerotic lesions by ImageJ software , 2017 .

[3]  W. Cai,et al.  Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators , 2018, ACS nano.

[4]  Lingyun Wang,et al.  Highly Flexible and Transparent Polyionic‐Skin Triboelectric Nanogenerator for Biomechanical Motion Harvesting , 2018, Advanced Energy Materials.

[5]  A. de Mel,et al.  A current affair: electrotherapy in wound healing , 2017, Journal of multidisciplinary healthcare.

[6]  B. Reid,et al.  The Electrical Response to Injury: Molecular Mechanisms and Wound Healing. , 2014, Advances in wound care.

[7]  Z. Suo,et al.  Bonding dissimilar polymer networks in various manufacturing processes , 2018, Nature Communications.

[8]  Bikramjit Basu,et al.  Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective. , 2018, Biomaterials.

[9]  Cheng Xu,et al.  Quantifying the triboelectric series , 2019, Nature Communications.

[10]  Sunglok Choi,et al.  Electroactive Soft Photonic Devices for the Synesthetic Perception of Color and Sound , 2018, Advanced materials.

[11]  Min Zhao,et al.  Application of direct current electric fields to cells and tissues in vitro and modulation of wound electric field in vivo , 2006, Nature Protocols.

[12]  Min Zhao,et al.  Electrical fields in wound healing-An overriding signal that directs cell migration. , 2009, Seminars in cell & developmental biology.

[13]  Byung-Soo Kim,et al.  Therapeutic Angiogenesis via Solar Cell-Facilitated Electrical Stimulation. , 2017, ACS applied materials & interfaces.

[14]  Ze Zhang,et al.  Electrical Stimulation Promotes Wound Healing by Enhancing Dermal Fibroblast Activity and Promoting Myofibroblast Transdifferentiation , 2013, PloS one.

[15]  J. Albeck,et al.  Controlling ERK Activation Dynamics in Mammary Epithelial Cells with Alternating Electric Fields through Microelectrodes. , 2019, Nano letters.

[16]  Min Zhao,et al.  Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors , 2003, Journal of Cell Science.

[17]  Tae-Jin Lee,et al.  Zinc Oxide Nanorod‐Based Piezoelectric Dermal Patch for Wound Healing , 2017 .

[18]  Zhuo Liu,et al.  Piezoelectric nanofibrous scaffolds as in vivo energy harvesters for modifying fibroblast alignment and proliferation in wound healing , 2018 .

[19]  Seungjin Nam,et al.  Textile Resistance Switching Memory for Fabric Electronics , 2017 .

[20]  H. Levinson A Paradigm of Fibroblast Activation and Dermal Wound Contraction to Guide the Development of Therapies for Chronic Wounds and Pathologic Scars. , 2013, Advances in wound care.

[21]  Xiuli Fu,et al.  Machine‐Washable Textile Triboelectric Nanogenerators for Effective Human Respiratory Monitoring through Loom Weaving of Metallic Yarns , 2016, Advanced materials.

[22]  J. R. Sharpe,et al.  Wound contraction is significantly reduced by the use of microcarriers to deliver keratinocytes and fibroblasts in an in vivo pig model of wound repair and regeneration. , 2012, Tissue engineering. Part A.

[23]  D. Agrawal,et al.  Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy , 2016, Stem Cell Research & Therapy.

[24]  Choon Chiang Foo,et al.  Stretchable, Transparent, Ionic Conductors , 2013, Science.

[25]  J. Uitto,et al.  Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. , 1986, Dermatologic clinics.

[26]  Jennifer H. Shin,et al.  Physicochemically Tuned Myofibroblasts for Wound Healing Strategy , 2019, Scientific Reports.

[27]  Jin Qi,et al.  An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair , 2019, NPG Asia Materials.

[28]  D. Kaplan,et al.  Programmable Hydrogel Ionic Circuits for Biologically Matched Electronic Interfaces , 2018, Advanced materials.

[29]  Paul G Scott,et al.  Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis , 2007, Stem cells.

[30]  Wook Kim,et al.  Cam-based sustainable triboelectric nanogenerators with a resolution-free 3D-printed system , 2017 .

[31]  Min Zhang,et al.  Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing , 2015, Scientific Reports.

[32]  Yinghuai Qiang,et al.  Enhancing proliferation and migration of fibroblast cells by electric stimulation based on triboelectric nanogenerator , 2019, Nano Energy.

[33]  Joo Chuan Yeo,et al.  Highly Stretchable, Weavable, and Washable Piezoresistive Microfiber Sensors. , 2018, ACS applied materials & interfaces.

[34]  T. Watson,et al.  Bioelectricity and microcurrent therapy for tissue healing – a narrative review , 2009 .

[35]  Zhigang Suo,et al.  Ionic skin , 2014, Advanced materials.

[36]  Jeong-Yun Sun,et al.  Hydrogel soft robotics , 2020, Materials Today Physics.

[37]  Yongliang Wang,et al.  Pulsed electrical stimulation modulates fibroblasts' behaviour through the Smad signalling pathway , 2017, Journal of tissue engineering and regenerative medicine.

[38]  Dukhyun Choi,et al.  Transparent and attachable ionic communicators based on self-cleanable triboelectric nanogenerators , 2018, Nature Communications.

[39]  F. Gottrup,et al.  Outcomes in controlled and comparative studies on non-healing wounds: recommendations to improve the quality of evidence in wound management. , 2013, Journal of wound care.