Skip to main content

Advertisement

Log in

A contactless electrical stimulator: application to fabricate functional skeletal muscle tissue

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Engineered skeletal muscle tissues are ideal candidates for applications in drug screening systems, bio-actuators, and as implantable constructs in tissue engineering. Electrical field stimulation considerably improves the differentiation of muscle cells to muscle myofibers. Currently used electrical stimulators often use direct contact of electrodes with tissue constructs or their culture medium, which may cause hydrolysis of the culture medium, joule heating of the medium, contamination of the culture medium due to products of electrodes corrosion, and surface fouling of electrodes. Here, we used an interdigitated array of electrodes combined with an isolator coverslip as a contactless platform to electrically stimulate engineered muscle tissue, which eliminates the aforementioned problems. The effective stimulation of muscle myofibers using this device was demonstrated in terms of contractile activity and higher maturation as compared to muscle tissues without applying the electrical field. Due to the wide array of potential applications of electrical stimulation to two- and three-dimensional (2D and 3D) cell and tissue constructs, this device could be of great interest for a variety of biological applications as a tool to create noninvasive, safe, and highly reproducible electric fields.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • C. Adam, Endogenous musculoskeletal tissue engineering - a focused perspective. Cell Tissue Res. 347, 489–499 (2012)

    Article  Google Scholar 

  • S. Ahadian, J. Ramón-Azcón, S. Ostrovidov, G. Camci-Unal, V. Hosseini, H. Kaji, K. Ino, H. Shiku, A. Khademhosseini, T. Matsue, Interdigitated array of Pt electrodes as a new platform for the electrical stimulation of engineered muscle tissue. Lab Chip. 12, 3494–3503 (2012)

    Google Scholar 

  • S. Arber, G. Halder, P. Caroni, Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 79, 221–231 (1994)

    Article  Google Scholar 

  • H. Aubin, J.W. Nichol, C.B. Hutson, H. Bae, A.L. Sieminski, D.M. Cropek, P. Akhyari, A. Khademhosseini, Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31, 6941–6951 (2010)

    Article  Google Scholar 

  • D. Berdat, A.C. Martin Rodriguez, F. Herrera, M.A.M. Gijs, Label-free detection of DNA with interdigitated micro-electrodes in a fluidic cell. Lab Chip 8, 302–308 (2008)

    Article  Google Scholar 

  • W. Bian, M. Juhas, T.W. Pfeiler, N. Bursac, Local tissue geometry determines contractile force generation of engineered muscle networks. Tissue Eng. Part A. 18, 957–967 (2011)

    Article  Google Scholar 

  • P. Clark, G.A. Dunn, A. Knibbs, M. Peckham, Alignment of myoblasts on ultrafine gratings inhibits fusion in vitro. Int. J. Biochem. Cell Biol. 34, 816–825 (2002)

    Article  Google Scholar 

  • H. Fujita, T. Van Dau, K. Shimizu, R. Hatsuda, S. Sugiyama, E. Nagamori, Designing of a Si-MEMS device with an integrated skeletal muscle cell-based bio-actuator. Biomed. Microdevices 13, 123–129 (2011)

    Article  Google Scholar 

  • A.M. Ghaemmaghami, M.J. Hancock, H. Harrington, H. Kaji, A. Khademhosseini, Biomimetic tissues on a chip for drug discovery. Drug Discov. Today 17, 173–181 (2012)

    Article  Google Scholar 

  • D.B. Hibbert, K. Weitzner, B. Tabor, P. Carter, Mass changes and dissolution of platinum during electrical stimulation in artificial perilymph solution. Biomaterials 21, 2177–2182 (2000)

    Article  Google Scholar 

  • S. Hinds, W. Bian, R.G. Dennis, N. Bursac, The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle. Biomaterials 32, 3575–3583 (2011)

    Article  Google Scholar 

  • V. Hosseini, S. Ahadian, S. Ostrovidov, G. Camci-Unal, S. Chen, H. Kaji, M. Ramalingam, A. Khademhosseini, Engineered contractile skeletal muscle tissue on a microgrooved methacrylated gelatin substrate. Tissue Eng. Part A. (2012)

  • M. Hronik-Tupaj, D.L. Kaplan, A review of the responses of two- and three-dimensional engineered tissues to electric fields. Tissue Eng. Part B: Rev. 18, 167–180 (2012)

    Article  Google Scholar 

  • H. Kaji, T. Ishibashi, K. Nagamine, M. Kanzaki, M. Nishizawa, Electrically induced contraction of C2C12 myotubes cultured on a porous membrane-based substrate with muscle tissue-like stiffness. Biomaterials 31, 6981–6986 (2010)

    Article  Google Scholar 

  • A. Khademhosseini, R. Langer, J. Borenstein, J.P. Vacanti, Microscale technologies for tissue engineering and biology. Proc. Natl. Acad. Sci. U. S. A. 103, 2480–2487 (2006)

    Article  Google Scholar 

  • M. Koning, M.C. Harmsen, M.J.A. van Luyn, P.M.N. Werker, Current opportunities and challenges in skeletal muscle tissue engineering. J. Tissue Eng. Regen. Med. 3, 407–415 (2009)

    Article  Google Scholar 

  • S. Musa, D.R. Rand, C. Bartic, W. Eberle, B. Nuttin, G. Borghs, Coulometric detection of irreversible electrochemical reactions occurring at Pt microelectrodes used for neural stimulation. Anal. Chem. 83, 4012–4022 (2011)

    Article  Google Scholar 

  • K. Nagamine, T. Kawashima, T. Ishibashi, H. Kaji, M. Kanzaki, M. Nishizawa, Micropatterning contractile C2C12 myotubes embedded in a fibrin gel. Biotechnol. Bioengin. 105, 1161–1167 (2010)

    Google Scholar 

  • K. Nagamine, T. Kawashima, S. Sekine, Y. Ido, M. Kanzaki, M. Nishizawa, Spatiotemporally controlled contraction of micropatterned skeletal muscle cells on a hydrogel sheet. Lab Chip 11, 513–517 (2011)

    Article  Google Scholar 

  • T. Nedachi, H. Fujita, M. Kanzaki, Contractile C2C12 myotube model for studying exercise-inducible responses in skeletal muscle. Am. J. Physiol.-Endocrinol. Metab. 295, E1191–E1204 (2008)

    Article  Google Scholar 

  • M. Nishizawa, H. Nozaki, H. Kaji, T. Kitazume, N. Kobayashi, T. Ishibashi, T. Abe, Electrodeposition of anchored polypyrrole film on microelectrodes and stimulation of cultured cardiac myocytes. Biomaterials 28, 1480–1485 (2008)

    Article  Google Scholar 

  • H. Park, R. Bhalla, R. Saigal, Effects of electrical stimulation in C2C12 muscle constructs. J. Tissue Eng. Regen. Med. 2, 279–287 (2008)

    Article  Google Scholar 

  • K. Park, H.-J. Suk, D. Akin, R. Bashir, Dielectrophoresis-based cell manipulation using electrodes on a reusable printed circuit board. Lab Chip 9, 2224–2229 (2009)

    Article  Google Scholar 

  • N.A. Peppas, J.Z. Hilt, A. Khademhosseini, R. Langer, Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006)

    Article  Google Scholar 

  • J. Ramón-Azcón, S. Ahadian, R. Obregon, G. Camci-Unal, S. Ostrovidov, V. Hosseini, H. Kaji, K. Ino, H. Shiku, A. Khademhosseini, T. Matsue, Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells. Lab Chip 12, 2959–2969 (2012)

    Article  Google Scholar 

  • S.A. Riboldi, M. Sampaolesi, P. Neuenschwander, G. Cossu, S. Mantero, Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering. Biomaterials 26, 4606–4615 (2005)

    Article  Google Scholar 

  • C.A. Rossi, M. Pozzobon, P. De Coppi, Advances in musculoskeletal tissue engineering: moving towards therapy. Organogenesis 6, 167–172 (2010)

    Article  Google Scholar 

  • H. Shafiee, J. Caldwell, M. Sano, R. Davalos, Contactless dielectrophoresis: a new technique for cell manipulation. Biomed. Microdevices 11, 997–1006 (2009)

    Article  Google Scholar 

  • H. Shafiee, M.B. Sano, E.A. Henslee, J.L. Caldwell, R.V. Davalos, Selective isolation of live/dead cells using contactless dielectrophoresis (cDEP). Lab Chip 10, 438–445 (2010)

    Article  Google Scholar 

  • B.V. Slaughter, S.S. Khurshid, O.Z. Fisher, A. Khademhosseini, N.A. Peppas, Hydrogels in regenerative medicine. Adv. Mater. 21, 3307–3329 (2009)

    Article  Google Scholar 

  • H. Vandenburgh, High-content drug screening with engineered musculoskeletal tissues. Tissue Eng. Part B: Rev. 16, 55–64 (2009)

    Article  Google Scholar 

Download references

Acknowledgments

S.A. conceived the idea. S.A. and J.R. designed the research. S.A., J.R., H.K., H.S., A.K., and T.M. analyzed the results. S.A. wrote the paper. G.C-U. synthesized the GelMA hydrogel. S.A. and J.R. performed all other experiments. H.K., H.S., A.K., and T.M. supervised the research. All authors read the manuscript, commented on it, and approved its content. This work was supported by the World Premier International Research Center Initiative (WPI), MEXT, Japan.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ali Khademhosseini or Tomokazu Matsue.

Additional information

Samad Ahadian and Javier Ramón-Azcón contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 43 kb)

(WMV 17786 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahadian, S., Ramón-Azcón, J., Ostrovidov, S. et al. A contactless electrical stimulator: application to fabricate functional skeletal muscle tissue. Biomed Microdevices 15, 109–115 (2013). https://doi.org/10.1007/s10544-012-9692-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-012-9692-1

Keywords

Navigation