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PMID: 24009651 Published · epublish English Journal Article

In vitro electrical-stimulated wound-healing chip for studying electric field-assisted wound-healing process.

Biomicrofluidics ·Vol. 6 ·No. 3 ·2012-00-00 ·Pages 34117

Sun YS, Peng SW, Cheng JY

Abstract

The wound-healing assay is an easy and economical way to quantify cell migration under diverse stimuli. Traditional assays such as scratch assays and barrier assays are widely and commonly used, but neither of them can represent the complicated condition when a wound occurs. It has been suggested that wound-healing is related to electric fields, which were found to regulate wound re-epithelialization. As a wound occurs, the disruption of epithelial barrier short-circuits the trans-epithelial potential and then a lateral endogenous electric field is created. This field has been proved invitro as an important cue for guiding the migration of fibroblasts, macrophages, and keratinocytes, a phenomenon termed electrotaxis or galvanotaxis. In this paper, we report a microfluidic electrical-stimulated wound-healing chip (ESWHC) integrating electric field with a modified barrier assay. This chip was used to study the migration of fibroblasts under different conditions such as serum, electric field, and wound-healing-promoting drugs. We successfully demonstrate the feasibility of ESWHC to effectively and quantitatively study cell migration during wound-healing process, and therefore this chip could be useful in drug discovery and drug safety tests.

Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sun Yung-Shin
Research Center for Applied Sciences, Academia Sinica, Taipei City 11529, Taiwan.
Peng Shih-Wei
Cheng Ji-Yen
References (71)
71 references, click to expand
  1. Phagocytic and metabolic reactions to chronically implanted metal brain electrodes.
    Exp Neurol. 1984 Nov;86(2):171-82 PMID: 6489492
  2. Using quality of life assessment in wound care.
    Nurs Stand. 2002 Oct 23;17(6):59-60, 64, 67-8 PMID: 12434751
  3. Superoxide plays critical roles in electrotaxis of fibrosarcoma cells via activation of ERK and reorganization of the cytoskeleton.
    Free Radic Biol Med. 2012 May 1;52(9):1888-96 PMID: 22406317
  4. Cell migration.
    Curr Biol. 2003 Sep 30;13(19):R756-9 PMID: 14521851
  5. Electrical stimulation of excitable tissue: design of efficacious and safe protocols.
    J Neurosci Methods. 2005 Feb 15;141(2):171-98 PMID: 15661300
  6. Promotion of wound healing with electrical stimulation.
    Adv Wound Care. 1996 Sep-Oct;9(5):42-5 PMID: 9069747
  7. Involvement of NO/cGMP signaling in the apoptotic and anti-angiogenic effects of beta-lapachone on endothelial cells in vitro.
    J Cell Physiol. 2007 May;211(2):522-32 PMID: 17192848
  8. Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs.
    Bioelectromagnetics. 2009 Jan;30(1):29-35 PMID: 18618607
  9. Anti-inflammatory effects of beta-lapachone in lipopolysaccharide-stimulated BV2 microglia.
    Int Immunopharmacol. 2007 Apr;7(4):506-14 PMID: 17321474
  10. Cell migration/invasion assays and their application in cancer drug discovery.
    Biotechnol Annu Rev. 2005;11:391-421 PMID: 16216785
  11. Effects of electrical stimulation on wound healing in patients with diabetic ulcers.
    Diabetes Care. 1997 Mar;20(3):405-12 PMID: 9051395
  12. Suppression of tumor necrosis factor-activated nuclear transcription factor-kappaB, activator protein-1, c-Jun N-terminal kinase, and apoptosis by beta-lapachone.
    Biochem Pharmacol. 1999 Apr 1;57(7):763-74 PMID: 10075082
  13. Reactive oxygen species (ROS) are essential mediators in epidermal growth factor (EGF)-stimulated corneal epithelial cell proliferation, adhesion, migration, and wound healing.
    Exp Eye Res. 2009 Dec;89(6):876-86 PMID: 19635476
  14. In vitro and in vivo wound healing-promoting activities of beta-lapachone.
    Am J Physiol Cell Physiol. 2008 Oct;295(4):C931-43 PMID: 18650264
  15. Asymmetric cancer-cell filopodium growth induced by electric-fields in a microfluidic culture chip.
    Lab Chip. 2011 Feb 21;11(4):695-9 PMID: 21152515
  16. Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds.
    Biomicrofluidics. 2012 Mar;6(1):14102-1410214 PMID: 22288000
  17. A review of the biophysical basis for the clinical application of electric fields in soft-tissue repair.
    J Burn Care Rehabil. 1993 May-Jun;14(3):319-35 PMID: 8360237
  18. Mechanotransduction in endothelial cell migration.
    J Cell Biochem. 2005 Dec 15;96(6):1110-26 PMID: 16167340
  19. Cancer therapy with beta-lapachone.
    Curr Cancer Drug Targets. 2002 Sep;2(3):227-42 PMID: 12188909
  20. Electrical dimensions in cell science.
    J Cell Sci. 2009 Dec 1;122(Pt 23):4267-76 PMID: 19923270
  21. Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms.
    Bioorg Med Chem. 2008 Jan 15;16(2):668-74 PMID: 18029184
  22. Human keratinocytes migrate to the negative pole in direct current electric fields comparable to those measured in mammalian wounds.
    J Cell Sci. 1996 Jan;109 ( Pt 1):199-207 PMID: 8834804
  23. Reactive oxygen species as intracellular messengers during cell growth and differentiation.
    Cell Physiol Biochem. 2001;11(4):173-86 PMID: 11509825
  24. Collective cell migration in morphogenesis and cancer.
    Int J Dev Biol. 2004;48(5-6):441-9 PMID: 15349818
  25. Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers.
    Biochemistry. 2005 May 10;44(18):6900-9 PMID: 15865435
  26. A transparent cell-culture microchamber with a variably controlled concentration gradient generator and flow field rectifier.
    Biomicrofluidics. 2008 Jun 17;2(2):24105 PMID: 19693408
  27. Direct-current electrical field guides neuronal stem/progenitor cell migration.
    Stem Cells. 2008 Aug;26(8):2193-200 PMID: 18556511
  28. Endogenous electric fields in embryos during development, regeneration and wound healing.
    Radiat Prot Dosimetry. 2003;106(4):375-83 PMID: 14690282
  29. Gene expression of human lung cancer cell line CL1-5 in response to a direct current electric field.
    PLoS One. 2011;6(10):e25928 PMID: 21998723
  30. Estrogen-induced reactive oxygen species-mediated signalings contribute to breast cancer.
    Biochim Biophys Acta. 2011 Jan;1815(1):115-33 PMID: 21036202
  31. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.
    Nature. 2006 Jul 27;442(7101):457-60 PMID: 16871217
  32. A comparative study of the effects of electrical stimulation and laser treatment on experimental wound healing in rats.
    J Rehabil Res Dev. 2004 Mar;41(2):147-54 PMID: 15558369
  33. Movements of cultured corneal epithelial cells and stromal fibroblasts in electric fields.
    Invest Ophthalmol Vis Sci. 1990 Nov;31(11):2278-82 PMID: 2242993
  34. Electrotherapy for acceleration of wound healing: low intensity direct current.
    Arch Phys Med Rehabil. 1985 Jul;66(7):443-6 PMID: 3893385
  35. A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods.
    BMC Biotechnol. 2004 Sep 09;4:21 PMID: 15357872
  36. Comparison of antibacterial and antifungal activities of lapachol and beta-lapachone.
    Planta Med. 1994 Aug;60(4):373-4 PMID: 7938274
  37. Directional protrusive pseudopodial activity and motility in macrophages induced by extracellular electric fields.
    Cell Motil. 1982;2(3):243-55 PMID: 6816471
  38. Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway.
    Cancer Res. 1999 Jan 15;59(2):391-8 PMID: 9927052
  39. Microfluidic device for studying cell migration in single or co-existing chemical gradients and electric fields.
    Biomicrofluidics. 2012 Jun;6(2):24121-2412113 PMID: 22670168
  40. Imaging the electric field associated with mouse and human skin wounds.
    Wound Repair Regen. 2008 May-Jun;16(3):432-41 PMID: 18471262
  41. Role of boundary conditions in an experimental model of epithelial wound healing.
    Am J Physiol Cell Physiol. 2006 Jul;291(1):C68-75 PMID: 16495370
  42. Electric stimulation of protein and DNA synthesis in human fibroblasts.
    FASEB J. 1987 Nov;1(5):398-402 PMID: 3678699
  43. The electric field near human skin wounds declines with age and provides a noninvasive indicator of wound healing.
    Wound Repair Regen. 2011 Sep-Oct;19(5):645-55 PMID: 22092802
  44. Cell-based sensors for quantifying the physiological impact of microsystems.
    Integr Biol (Camb). 2011 Jan;3(1):48-56 PMID: 20949196
  45. Current therapies for wound healing: electrical stimulation, biological therapeutics, and the potential for gene therapy.
    Int J Dermatol. 1999 Nov;38(11):808-17 PMID: 10583612
  46. Direct current electrical fields induce apoptosis in oral mucosa cancer cells by NADPH oxidase-derived reactive oxygen species.
    Bioelectromagnetics. 2008 Jan;29(1):47-54 PMID: 17786977
  47. Electrotaxis of lung cancer cells in a multiple-electric-field chip.
    Biosens Bioelectron. 2009 Aug 15;24(12):3510-6 PMID: 19497728
  48. Effects of electrical fields on cardiomyocyte differentiation of embryonic stem cells.
    J Cell Biochem. 1999 Dec 15;75(4):710-23 PMID: 10572253
  49. Response of C3H/10T1/2 fibroblasts to an external steady electric field stimulation. Reorientation, shape change, ConA receptor and intramembranous particle distribution and cytoskeleton reorganization.
    Exp Cell Res. 1984 Nov;155(1):92-104 PMID: 6541591
  50. Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species.
    Exp Cell Res. 2009 Dec 10;315(20):3611-9 PMID: 19720058
  51. Electric field-directed fibroblast locomotion involves cell surface molecular reorganization and is calcium independent.
    J Cell Biol. 1994 Oct;127(1):117-28 PMID: 7929557
  52. Effect of pulse direct current signals on electrotactic movement of nematodes Caenorhabditis elegans and Caenorhabditis briggsae.
    Biomicrofluidics. 2011 Dec;5(4):44116-441169 PMID: 22232698
  53. The glabrous epidermis of cavies contains a powerful battery.
    Am J Physiol. 1982 Mar;242(3):R358-66 PMID: 7065232
  54. Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS.
    Am J Physiol Heart Circ Physiol. 2012 Jan 1;302(1):H105-14 PMID: 22003059
  55. Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase; ROS-elicited Ca2+ stimulates ERK, CREB, early genes.
    J Cell Physiol. 2006 Nov;209(2):379-88 PMID: 16897752
  56. Polarity effects on wound healing using electric stimulation in rabbits.
    Arch Phys Med Rehabil. 1989 Aug;70(8):624-7 PMID: 2788400
  57. A role for endogenous electric fields in wound healing.
    Curr Top Dev Biol. 2003;58:1-26 PMID: 14711011
  58. Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells.
    Cancer Res. 2007 Nov 1;67(21):10260-7 PMID: 17974967
  59. Orientation and directed migration of cultured corneal epithelial cells in small electric fields are serum dependent.
    J Cell Sci. 1996 Jun;109 ( Pt 6):1405-14 PMID: 8799828
  60. Microfluidic devices for studying chemotaxis and electrotaxis.
    Trends Cell Biol. 2011 Aug;21(8):489-97 PMID: 21665472
  61. Embryonic fibroblast motility and orientation can be influenced by physiological electric fields.
    J Cell Biol. 1984 Jan;98(1):296-307 PMID: 6707093
  62. Antiplasmodial activity of naphthoquinones related to lapachol and beta-lapachone.
    Chem Biodivers. 2005 Feb;2(2):264-74 PMID: 17191979
  63. Differential effects of matrix and growth factors on endothelial and fibroblast motility: application of a modified cell migration assay.
    J Cell Biochem. 2006 Dec 15;99(6):1536-52 PMID: 16817234
  64. Effect of transcutaneous electrostimulation on the cell composition of skin exudate.
    Acta Physiol Pol. 1986 Jan-Feb;37(1):41-6 PMID: 3491491
  65. Electrical and ionic controls of tissue cell locomotion in DC electric fields.
    J Neurosci Res. 1985;13(1-2):223-44 PMID: 3973934
  66. Induction of Egr-1 is associated with anti-metastatic and anti-invasive ability of beta-lapachone in human hepatocarcinoma cells.
    Biosci Biotechnol Biochem. 2007 Sep;71(9):2169-76 PMID: 17827686
  67. Intrinsic electric fields promote epithelization of wounds in the newt, Notophthalmus viridescens.
    Dev Biol. 1991 Aug;146(2):377-85 PMID: 1864462
  68. Wounding induces motility in sheets of corneal epithelial cells through loss of spatial constraints: role of heparin-binding epidermal growth factor-like growth factor signaling.
    J Biol Chem. 2004 Jun 4;279(23):24307-12 PMID: 15039441
  69. Electrotaxis of Caenorhabditis elegans in a microfluidic environment.
    Lab Chip. 2010 Jan 21;10(2):220-6 PMID: 20066250
  70. Histopathological evaluation of materials implanted in the cerebral cortex.
    Acta Neuropathol. 1978 Feb 20;41(2):145-55 PMID: 636844
  71. Experimental wound healing with electrical stimulation.
    Artif Organs. 1999 May;23(5):460-2 PMID: 10378943
Article Info
Journal
Biomicrofluidics
Abbr.
Biomicrofluidics
ISSN
1932-1058
Published
2012-00-00
Epub
2012-00-05
Pages
34117
Language
English
Region
United States
NLM ID
101293825
PMCID
PMC3448595
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