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Acceleration of cutaneous healing by electrical stimulation: Degenerate electrical waveform down‐regulates inflammation, up‐regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study
Author(s) -
Sebastian Anil,
Syed Farhatullah,
Perry Donna,
Balamurugan Vinayagapriya,
Colthurst James,
Chaudhry Iskander H.,
Bayat Ardeshir
Publication year - 2011
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2011.00736.x
Subject(s) - angiogenesis , cd31 , wound healing , granulation tissue , medicine , immunohistochemistry , inflammation , h&e stain , pathology , biopsy , stimulation , andrology , endocrinology , immunology
We previously demonstrated the beneficial effect of a novel electrical stimulation ( ES ) waveform, degenerate wave ( DW ) on skin fibroblasts, and now hypothesize that DW can enhance cutaneous wound healing in vivo . Therefore, a punch biopsy was taken from the upper arm of 20 volunteers on day 0 and repeated on day 14 ( NSD14 ). A contralateral upper arm biopsy was taken on day 0 and treated with DW for 14 days prior to a repeat biopsy on day 14 ( ESD14 ). A near‐completed inflammatory stage of wound healing in ESD14 , compared to NSD14 was demonstrated by up‐regulation of interleukin‐10 and vasoactive intestinal peptide using quantitative real time polymerase chain reaction and down‐regulation of CD3 by immunohistochemistry ( IHC ) ( p < 0.05). In addition to up‐regulation ( p < 0.05) of mRNA transcripts for re‐epithelialization and angiogenesis, IHC showed significant overexpression ( p < 0.05) of CD31 (15.5%), vascular endothelial growth factor (66%), and M elan A (8.6 cells/0.95 mm 2 ) in ESD14 compared to NSD14 (9.5%, 38% and 4.3 cells/0.95 mm 2 , respectively). Furthermore, granulation tissue formation (by hematoxylin and eosin staining), and myofibroblastic proliferation demonstrated by alpha‐smooth muscle actin (62.7%) plus CD3+ T lymphocytes (8.1%) showed significant up‐regulation ( p < 0.05) in NSD14 . In the remodeling stage, mRNA transcripts for fibronectin, collagen IV (by IHC , 14.1%) and mature collagen synthesis (by H erovici staining, 71.44%) were significantly up‐regulated ( p < 0.05) in ESD14 . Apoptotic ( TUNEL assay) and proliferative cells ( Ki67 ) were significantly up‐regulated ( p < 0.05) in NSD14 (5.34 and 11.9 cells/0.95 mm 2 ) while the proliferation index of ESD14 was similar to normal skin. In summary, cutaneous wounds receiving DW electrical stimulation display accelerated healing seen by reduced inflammation, enhanced angiogenesis and advanced remodeling phase.