Elsevier

Biomaterials

Volume 285, June 2022, 121479
Biomaterials

Flexible patch with printable and antibacterial conductive hydrogel electrodes for accelerated wound healing

https://doi.org/10.1016/j.biomaterials.2022.121479Get rights and content

Abstract

Electrical stimulation can facilitate wound healing with high efficiency and limited side effects. However, current electrical stimulation devices have poor conformability with wounds due to their bulky nature and the rigidity of electrodes utilized. Here, a flexible electrical patch (ePatch) made with conductive hydrogel as electrodes to improve wound management was reported. The conductive hydrogel was synthesized using silver nanowire (AgNW) and methacrylated alginate (MAA), with the former chosen as the electrode material considering its antibacterial properties, and the latter used due to its clinical suitability in wound healing. The composition of the hydrogel was optimized to enable printing on medical-grade patches for personalized wound treatment. The ePatch was shown to promote re-epithelization, enhance angiogenesis, mediate immune response, and prevent infection development in the wound microenvironment. In vitro studies indicated an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to electrical stimulation. An in vivo study in the Sprague-Dawley rat model revealed a rapid wound closure within 7 days compared to 20 days of usual healing process in rodents.

Graphical abstract

A flexible electrical patch (ePatch) with conductive hydrogel was designed to accelerate wound healing. The conductive hydrogel contains silver nanowire and methacrylated alginate, which endow antibacterial efficacy and printability to the ePatch. Healing speed was promoted in a Sprague Dawley rat-based wound model.

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Section snippets

Credit author statement

Canran Wang: Methodology, Investigation, Validation, Writing - Original Draft. Xing Jiang: Methodology, Investigation, Validation, Writing - Original Draft. Han-Jun Kim: Methodology, Investigation, Validation, Writing - Original Draft. Shiming Zhang: Methodology, Investigation. Xingwu Zhou: Investigation. Yi Chen: Investigation. Haonan Ling: Investigation. Yumeng Xu: Investigation. Zhaowei Chen: Investigation. Moyuan Qu: Investigation. Li Ren: Investigation. Jixiang Zhu: Investigation. Alberto

Preparation and characterization of AgNW-MAA ink

Conductive hydrogel has been investigated for a variety of medical applications. They are generally composed of conductive nanomaterials and organic binders [52]. In our study, MAA was chosen as the organic binder, and AgNW was selected as the conductive nanomaterial [53,54]. AgNWs and MAA were synthesized and characterized by scanning electron microscope (SEM) and nuclear magnetic resonance (NMR), respectively (Fig. S1, S2). As shown in Fig. S1, the synthesized AgNWs had a large

Conclusion

In summary, we have developed a flexible ePatch based on conductive hydrogel for accelerated wound healing. Conductive AgNW used in the hydrogel conferred antibacterial properties to the ePatch. Moreover, clinically used alginate hydrogel endowed the ePatch with good biocompatibility and printability. The double-crosslinked network enhanced the mechanical strength of the conductive hydrogel. By delivering EF to the wound, our ePatch was shown to boost the expression of growth factors by NIH 3T3

Materials

Polyvinylpyrrolidone (PVP360, Mw ≈ 360,000 g mol−1), silver nitrate, sodium chloride, sodium alginate (A2033, medium viscosity), 2-Aminoethyl methacrylate hydrochloride (AEMA, 900,652), polydimethylsiloxane (PHR1518, PDMS) and calcium chloride (C1016) were purchased from Sigma-Aldrich. Fibronectin and polyimide tapes were supplied by Thermofisher Scientific.

Synthesis of the silver nanowire

AgNW was synthesized by reducing silver nitrate according to previous report. Briefly, 1 g of polyvinylpyrrolidone was mixed with 14 mg

Data availability

The experimental data required to reproduce the findings from this study will be made available to interested investigators upon request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

The authors acknowledge funding from the National Institutes of Health (EB024403, EB023052, GM126831, and HL140618).

References (82)

  • C. Xu et al.

    Skin-interfaced sensors in digital medicine: from materials to applications

    Matter

    (2020)
  • H. Chen et al.

    An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair

    NPG Asia Mater.

    (2019)
  • B. ter Horst et al.

    Advances in keratinocyte delivery in burn wound care

    Adv. Drug Deliv. Rev.

    (2018)
  • Y. Zhu et al.

    Modulation of macrophages by bioactive glass/sodium alginate hydrogel is crucial in skin regeneration enhancement

    Biomaterials

    (2020)
  • W.Y. Ng et al.

    Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing

    Int. J. Biol. Macromol.

    (2017)
  • R. Rudež et al.

    Preparation and influence of highly concentrated screen-printing inks on the development and characteristics of thick-film varistors

    J. Eur. Ceram. Soc.

    (2015)
  • Y. Li et al.

    Engineering cell alignment in vitro

    Biotechnol. Adv.

    (2014)
  • H. Zhuang et al.

    Electrical stimulation induces the level of TGF-beta 1 mRNA in osteoblastic cells by a mechanism involving calcium/calmodulin pathway

    Biochem. Biophys. Res. Commun.

    (1997)
  • A.R. Unnithan et al.

    Electrospun zwitterionic nanofibers with in situ decelerated epithelialization property for non-adherent and easy removable wound dressing application

    Chem. Eng. J.

    (2016)
  • A. Gupta et al.

    A time course study for the development of an immunocompromised wound model, using hydrocortisone

    J. Pharmacol. Toxicol. Methods

    (1999)
  • C. Bradford et al.

    In vitro study of sustained antimicrobial activity of a new silver alginate dressing

    J. Am. Col. Certif. Wound Spec.

    (2009)
  • T.N. Demidova-Rice et al.

    Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care

    Adv. Skin Wound Care

    (2012)
  • Z. Iheozor-Ejiofor et al.

    Negative pressure wound therapy for open traumatic wounds

    Cochrane Database Syst. Rev.

    (2018)
  • Y. Xi et al.

    Bioactive anti-inflammatory, antibacterial, antioxidative silicon-based nanofibrous dressing enables cutaneous tumor photothermo-chemo therapy and infection-induced wound healing

    ACS Nano

    (2020)
  • N. Mookherjee et al.

    Antimicrobial host defence peptides: functions and clinical potential

    Nat. Rev. Drug Discov.

    (2020)
  • R.G. Frykberg et al.

    Challenges in the treatment of chronic wounds

    Adv. Wound Care

    (2015)
  • M. Mochizuki et al.

    Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing

    Nat. Biomed. Eng.

    (2020)
  • H. Lev-Tov

    Small spice for big wounds: can curcumin close the gap?

    Sci. Transl. Med.

    (2017)
  • A.L. Brundage et al.

    Methods for external disinfection of blow fly (Diptera: calliphoridae) eggs prior to use in wound debridement therapy

    Wound Repair Regen.

    (2016)
  • M.L. Costa

    Negative pressure wound therapy for open fractures-reply

    JAMA

    (2018)
  • J.F. Holmes et al.

    Effect of abdominal ultrasound on clinical care, outcomes, and resource use among children with blunt torso trauma: a randomized clinical trial

    JAMA

    (2017)
  • C.K. Sen et al.

    Human skin wounds: a major and snowballing threat to public health and the economy

    Wound Repair Regen.

    (2009)
  • G. Thakral et al.

    Electrical stimulation to accelerate wound healing

    Diabet. Foot Ankle

    (2013)
  • S. Kargozar et al.

    Nanotechnology for Angiogenesis: Opportunities and Challenges

    (2020)
  • M. Ashrafi et al.

    The efficacy of electrical stimulation in lower extremity cutaneous wound healing: a systematic review

    Exp. Dermatol.

    (2017)
  • G. Yao et al.

    Self-activated electrical stimulation for effective hair regeneration via a wearable omnidirectional pulse generator

    ACS Nano

    (2019)
  • S. Roy et al.

    Disposable patterned electroceutical dressing (PED-10) is safe for treatment of open clinical chronic wounds

    Adv. Wound Care

    (2019)
  • T. Someya et al.

    Toward a new generation of smart skins

    Nat. Biotechnol.

    (2019)
  • B. Yang et al.

    Injectable Adhesive self-healing multicross-linked double-network hydrogel facilitates full-thickness skin wound healing

    ACS Appl. Mater. Interfaces

    (2020)
  • Y. Chang et al.

    First Decade of Interfacial Iontronic Sensing: from Droplet Sensors to Artificial Skins, Advanced Materials

    (2020)
  • S.R. Madhvapathy et al.

    Reliable, low-cost, fully integrated hydration sensors for monitoring and diagnosis of inflammatory skin diseases in any environment

    Sci. Adv.

    (2020)
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    These authors contributed equally to this work.

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