Biobattery-Powered Wearable Electrostimulated Patch Based On Viologen Hydrogel

Electrostimulation is an emerging method of treating skin diseases in recent years,which allows drugs to overcome the barrier of the stratum corneum and enter the body transdermally.In addition,electrical stimulation provides direct interaction with cells to promote cell migration and proliferation.Self-powered electrostimulated patches have received widespread attention in recent years because of the advantages of good patient compliance,user friendliness and integratability.For self-powered electrostimulated systems,the energy used for powering systems is essential.Commercially available self-powered electrostimulated patches still employ traditional batteries as energy devices that enable long-term stable treatment processes,however,the rigidity and size of the battery limits the integration of advanced self-powered electrostimulated patches.Therefore,it is crucial to develop novel flexible energy systems.The electrode,as an essential part of the patch,requires direct contact with the skin and forms a bioelectronic interface.Electrical signal conversion at the bioelectronic interface closely related to the therapeutic effect of the patch,so the interface material usually requires such properties as high electrical conductivity,biocompatibility,antibacterial properties and mechanical adaptability.In this paper,we design and prepare various novel viologen-based conductive hydrogels to investigate the bioelectronic interface properties between hydrogels and skin.The hydrogels used as integrated electrodes for both the electrochemical energy storage and electrical stimulation response to build wearable electrical stimulation patches driven by biocompatible batteries.The paper contains three major works as follows.（1）Through molecular design,we synthesized an asymmetric viologen monomer BV and developed a viologen-based conductive hydrogel P（AM-HAM-BV）,which has high electro-responsivity and drug loading capability.The hydrogel designed as an optimal bioelectronic interface material,specifically including soft properties,high ionic conductivity,low tissue impedance,high adhesion,good cytocompatibility,and antibacterial properties.P（AM-HAM-BV）hydrogel provides stable high-dose encapsulation of ATP through electrostatic interactions and borate ester structure,achieving high release efficiency（65%）driven by low voltage（-1.0 V）.We explored the possibility of using hydrogel P（AM-HAM-BV）as a drug-loading cathode for an integrated Mg biobattery to design a novel Mg battery-powered iontophoresis patch.We have demonstrated a stable and efficient drug delivery process powered by the battery,which has the potential for long-term and efficient therapeutic administration.（2）We have synthesized an asymmetric viologen monomer SV and developed a viologen-based conductive hydrogel P（AM-co-SV）,which is an excellent bioelectronic interface material with similar softness as biological tissues,low epidermal tissue impedance,high biocompatibility for directly cell culture,excellent antibacterial ability,and electrochromic properties.The hydrogel allows effective loading of dexamethasone（Dex）by electrostatic interactions and effective drug delivery at low driving voltages,with the release profile conforming to the reduction process of viologen.The P（AM-co-SV）hydrogel drug reservoir was used as the cathode of the Mg battery,which integrated drug loading electrode enabled simplified wearable self-powered iontophoresis and eliminated the interfacial impedance between the electrode and drug reservoir.The prepared Mg biobattery provided an area energy density of 3.57m Wh cm^-2 at an area power density of 11μW cm^-2.The maximum area energy density reported in this work is higher than other self-powered iontophoresis patch drug-delivery devices.The therapeutic efficacy of this Mg biobattery-driven iontophoresis patch demonstrated by treatment of mice with imiquimod-induced psoriasis,which restored the skin of the affected mice to normal within 5 days.This work may provide a novel non-invasive treatment for chronic epidermal diseases.（3）From the material design perspective,a dual-network material design strategy was introduced to enhance the mechanical strength of the material.First,polyvinyl alcohol（PVA）introduced into the gel network to form a gel network cross-linked by hydrogen bonding through a freeze-thaw cycling process.Secondly,long chain alkyl groups introduced into the structure of viologen to increase the flexibility of viologen molecules while avoiding intermolecular stacking.The double network viologen hydrogel P（AM-co-Ba V）/PVA has high toughness(17 k J m^-3),near human skin stretch length（270%）,low epidermal impedance,low cytotoxicity and excellent antibacterial properties,which allows to be used as a wound dressing.P（AM-co-Ba V）/PVA hydrogel serves both as a cathode for biocompatible zinc battery and as a wound dressing in the electrostimulus patch.The zinc battery-powered electrical stimulation patch provides a consistent electrical signal output with the ability to effectively promote the proliferation of fibroblasts in vitro.Applying the patch to the full-thickness wound of rats accelerated the area closure efficiency of the wound site by more than 97%within 14 days,contributing to the thickening of collagen deposition and revascularization.