Cardiac toxicity screening using polymeric cantilever integrated with cell stimulators

This paper describes a smart cantilever device to precisely monitor the drug-induced contraction forces of cardiac muscle cells. The cantilever device is composed of two parallel microelectrodes and 3D micro-patterns on the surface. The microelectrodes are utilized to synchronize beating of individual cell during drug screening experiments. These also enhance the expression of connexin 43 (Cx-43) of gap junctions that electrically couple cardiac cells. The optimized 3D microstructures greatly improve the contraction force. These physical stimulations (electrical and mechanical) are very effective to mature cardiac cells obtained from neonatal rats. The fabricated cantilever devices are also employed for pre-screening of drugs in cardiac toxicity.

[1]  Jason Lazarou,et al.  Incidence of Adverse Drug Reactions in Hospitalized Patients , 1999 .

[2]  Young-Soo Choi,et al.  Surface-patterned SU-8 cantilever arrays for preliminary screening of cardiac toxicity. , 2016, Biosensors & bioelectronics.

[3]  Gregory T. A. Kovacs,et al.  Current-Controlled Electrical Point-Source Stimulation of Embryonic Stem Cells , 2009, Cellular and molecular bioengineering.

[4]  Yen Chang,et al.  Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating. , 2013, Biomaterials.

[5]  R. Curi,et al.  Effects of moderate electrical stimulation on reactive species production by primary rat skeletal muscle cells: Cross talk between superoxide and nitric oxide production , 2012, Journal of cellular physiology.

[6]  Gordana Vunjak-Novakovic,et al.  Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes , 2016, Nature Communications.

[7]  J. Hescheler,et al.  Electrophysiological and Morphological Maturation of Murine Fetal Cardiomyocytes During Electrical Stimulation In Vitro , 2015, Journal of cardiovascular pharmacology and therapeutics.

[8]  N. Bursac,et al.  Biomechanics and Mechanotransduction in Cells and Tissues Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes , 2005 .

[9]  WeiningBian,et al.  Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells , 2006 .

[10]  Hui Ye,et al.  Neuron matters: electric activation of neuronal tissue is dependent on the interaction between the neuron and the electric field , 2015, Journal of NeuroEngineering and Rehabilitation.

[11]  L. Griffin,et al.  Neuromuscular Electrical Stimulation for Skeletal Muscle Function , 2012, The Yale journal of biology and medicine.

[12]  Joel Voldman,et al.  Surface-patterned electrode bioreactor for electrical stimulation. , 2010, Lab on a chip.

[13]  Wolfgang Eberle,et al.  Localized electrical stimulation of in vitro neurons using an array of sub-cellular sized electrodes. , 2010, Biosensors & bioelectronics.