한빛사논문
Shanika Karunasagara a,b,c, Buuvee Bayarkhangai a,b,c, Hye-Won Shim a,b,c, Han-Jin Bae a,b,c, Hwalim Lee d, Ali Taghizadeh a,b,c, Yunseong Ji a, Nandin Mandakhbayar a,b,c, Hye Sung Kim a,b,c, Jeongeun Hyun a,b,c,e, Tae-Jin Kim h,i, Jung-Hwan Lee a,b,c,d,e,f,g, Hae-Won Kim a,b,c,d,e,f,g
aInstitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea
bDepartment of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
cMechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea
dDepartment of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
eDepartment of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
fCell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea
gUCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
hDepartment of Integrated Biological Science, Pusan National University Pusan, 46241, Republic of Korea
iDepartment of Biological Sciences, Pusan National University Pusan, 46241, Republic of Korea
Corresponding authors: Jung-Hwan Lee, Hae-Won Kim
Abstract
Electrical stimulation (ES) through biomaterials and devices has been implicated in activating diverse cell behaviors while facilitating tissue healing process. Despite its significance in modulating biological events, the mechanisms governing ES-activated cellular phenomena remain largely elusive. Here, we demonstrated that millisecond-pulsed temporal ES profoundly impacted a spectrum of cellular events across the membrane-cytosol-nuclear space. These include activated ion channels, intracellular calcium influx, actomyosin contractility, cell migration and proliferation, and secretome release. Such events were coordinated mainly through ES-activated ion channels and calcium oscillation dynamics. Notably, ES increased the chromatin accessibility of genes, particularly those associated with the ES-activated cellular events, underscoring the significance of epigenetic changes in ES-induced behavioral outcomes. We identified histone acetylation (mediated by histone acetyltransferases), among other chromatin modifications, is key in reshaping the chromatin landscape upon ES. These observations were further validated through experiments involving ex vivo skin tissue samples, including activated ion channels and calcium influx, increased cell proliferation and actomyosin contractility, elevated secretome profile, and more accessible chromatin structure following ES. This work provides novel insights into the mechanisms underlying ES-activated cell and tissue events, ultimately guiding design principles for the development of electrical devices and materials effective for tissue repair and wound healing.
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