Electrical Modeling of the Growth and Differentiation of Skeletal Myoblasts Cell Cultures for Tissue Engineering

In tissue engineering, of utmost importance is the control of tissue formation, in order to form tissue constructs of clinical relevance. In this work, we present the use of an impedance spectroscopy technique for the real-time measurement of the dielectric properties of skeletal myoblast cell cultures. The processes involved in the growth and differentiation of these cell cultures in skeletal muscle are studied. A circuit based on the oscillation-based test technique was used, avoiding the use of high-performance circuitry or external input signals. The effect of electrical pulse stimulation applied to cell cultures was also studied. The technique proved useful for monitoring in real-time the processes of cell growth and estimating the fill factor of muscular stem cells. Impedance spectroscopy was also useful to study the real-time monitoring of cell differentiation, obtaining different oscillation amplitude levels for differentiated and undifferentiated cell cultures. Finally, an electrical model was implemented to better understand the physical properties of the cell culture and control the tissue formation process.

[1]  Gloria Huertas,et al.  Towards Bio-Impedance based labs: A review , 2015, 2015 Conference on Design of Circuits and Integrated Systems (DCIS).

[2]  Mauro Serpelloni,et al.  A Review on Biomaterials for 3D Conductive Scaffolds for Stimulating and Monitoring Cellular Activities , 2019, Applied Sciences.

[3]  A. Yúfera,et al.  Electrical pulse stimulation of skeletal myoblasts cell cultures with simulated action potentials , 2019, Journal of tissue engineering and regenerative medicine.

[4]  Jari Hyttinen,et al.  Electric impedance of human embryonic stem cell-derived retinal pigment epithelium , 2011, Medical & Biological Engineering & Computing.

[5]  Gloria Huertas,et al.  The Bio-Oscillator: A Circuit for Cell-Culture Assays , 2015, IEEE Transactions on Circuits and Systems II: Express Briefs.

[6]  Alberto Olmo,et al.  Monitoring living cell assays with bio-impedance sensors , 2013 .

[7]  Philippe Renaud,et al.  In Vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays , 2009, IEEE Transactions on Biomedical Engineering.

[8]  Yudan Whulanza,et al.  Sensing scaffolds to monitor cellular activity using impedance measurements. , 2011, Biosensors & bioelectronics.

[9]  Gloria Huertas,et al.  An Empirical-Mathematical Approach for Calibration and Fitting Cell-Electrode Electrical Models in Bioimpedance Tests , 2018, Sensors.

[10]  G. Malliaras,et al.  Conducting Polymer Scaffolds Based on Poly(3,4-ethylenedioxythiophene) and Xanthan Gum for Live-Cell Monitoring , 2018, ACS omega.

[11]  Sung June Kim,et al.  Electrical stimulation-induced cell clustering in cultured neural networks , 2007, Medical & Biological Engineering & Computing.

[12]  K. Sarker,et al.  L6 myoblast differentiation is modulated by Cdk5 via the PI3K–AKT–p70S6K signaling pathway , 2004, Oncogene.

[13]  Gloria Huertas,et al.  Remote Sensing of Cell-Culture Assays , 2017 .

[14]  I. Giaever,et al.  Monitoring fibroblast behavior in tissue culture with an applied electric field. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Pierre O. Bagnaninchi,et al.  Real-time label-free monitoring of adipose-derived stem cell differentiation with electric cell-substrate impedance sensing , 2011, Proceedings of the National Academy of Sciences.

[16]  Binil Starly,et al.  Electrical Cell‐Substrate Impedance Spectroscopy Can Monitor Age‐Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation , 2016, Stem cells translational medicine.

[17]  R A Brown,et al.  3-D in vitro model of early skeletal muscle development. , 2003, Cell motility and the cytoskeleton.

[18]  G. Malliaras,et al.  Conducting Polymer Scaffolds based on PEDOT and Xanthan Gum for Live-Cell Monitoring , 2018 .

[19]  Hua Liao,et al.  Development and progress of engineering of skeletal muscle tissue. , 2009, Tissue engineering. Part B, Reviews.

[21]  Mauro Serpelloni,et al.  Preliminary Study of Inkjet Printed Sensors for Monitoring Cell Cultures , 2016 .

[22]  Sungbo Cho,et al.  Real-Time Monitoring of Neural Differentiation of Human Mesenchymal Stem Cells by Electric Cell-Substrate Impedance Sensing , 2011, Journal of biomedicine & biotechnology.

[23]  Kin Fong Lei,et al.  Real-time and non-invasive impedimetric monitoring of cell proliferation and chemosensitivity in a perfusion 3D cell culture microfluidic chip. , 2014, Biosensors & bioelectronics.

[24]  Sungbo Cho,et al.  Detection of the osteogenic differentiation of mesenchymal stem cells in 2D and 3D cultures by electrochemical impedance spectroscopy. , 2010, Journal of biotechnology.