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Effect of Periodical Tensile Stimulation on the Human Skin Equivalents by Magnetic Stretching Skin-on-a-Chip (MSSC)

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Abstract

The skin is the largest organ that protects the body from the outside and is subjected to constant physical stimulation, such as stretching. Although many studies currently focus on UV radiation and skin aging, few studies have been reported on the effects of excessive physical stimulation on the skin. We have developed a magnetic stretching skin-on-chip (MSSC) with a built-in electromagnet to apply magnetic field-based tensile stimulation. According to the 12-h cycle circadian locomotor output cycles kaput (CLOCK) gene expression, 5% tensile stimulation was added at 0.01 Hz for 12 h per day. Physical stress was applied during the 28 days of the skin regeneration cycle, and the tissue morphological changes, protein expression, and gene expression of skin equivalents were compared to previous study results of compressive stimulation (opposite mode of tensile) to confirm the effects. Comprehensively report the skin reaction depending on the type of stimulation. The expression of genes related to the epidermal barrier showed a similar tendency for both stimulation in the case of filaggrin, but the opposite tendency appeared for involucrin and keratin 10. The proteins that make up the dermis and epidermis also showed opposite trends in expression.

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References

  1. Kindred, C., Oresajo C.O., Halder R.M. (2009) Overview of the structure and function of ethnic skin. Nutritional Cosmetics pp. 47–62 Elsevier

  2. Rawlings, A., Harding, C.: Moisturization and skin barrier function. Dermatol. Ther. 17, 43–48 (2004)

    Article  Google Scholar 

  3. Ingber, D.: Mechanobiology and diseases of mechanotransduction. Ann. Med. 35, 564–577 (2003)

    Article  Google Scholar 

  4. DuFort, C.C., Paszek, M.J., Weaver, V.M.: Balancing forces: architectural control of mechanotransduction. Nat. Rev. Mol. Cell Biol. 12, 308–319 (2011)

    Article  CAS  Google Scholar 

  5. Nishimura, S., Seo, K., Nagasaki, M., Hosoya, Y., Yamashita, H., Fujita, H., et al.: Responses of single-ventricular myocytes to dynamic axial stretching. Prog. Biophys. Mol. Biol. 97, 282–297 (2008)

    Article  CAS  Google Scholar 

  6. Sniadecki, N.J., Lamb, C.M., Liu, Y., Chen, C.S., Reich, D.H.: Magnetic microposts for mechanical stimulation of biological cells: fabrication, characterization, and analysis. Rev. Sci. Instrum. 79, 044302 (2008)

    Article  Google Scholar 

  7. Tan, Y., Sun, D., Wang, J., Huang, W.: Mechanical characterization of human red blood cells under different osmotic conditions by robotic manipulation with optical tweezers. IEEE Trans. Biomed. Eng. 57, 1816–1825 (2010)

    Article  Google Scholar 

  8. Deguchi, S., Kudo, S., Matsui, T.S., Huang, W., Sato, M.: Piezoelectric actuator-based cell microstretch device with real-time imaging capability. AIP Adv. 5, 067110 (2015)

    Article  Google Scholar 

  9. Huang, Y., Nguyen, N.-T.: A polymeric cell stretching device for real-time imaging with optical microscopy. Biomed. Microdevice 15, 1043–1054 (2013)

    Article  CAS  Google Scholar 

  10. Nava, G., Bragheri, F., Yang, T., Minzioni, P., Osellame, R., Cristiani, I., et al.: All-silica microfluidic optical stretcher with acoustophoretic prefocusing. Microfluid. Nanofluid. 19, 837–844 (2015)

    Article  CAS  Google Scholar 

  11. He, Z., Potter, R., Li, X., Flessner, M.: Stretch of human mesothelial cells increases cytokine expression. Adv Perit Dial. 28, 2–9 (2012)

    Google Scholar 

  12. Greek, R., Menache, A.: Systematic reviews of animal models: methodology versus epistemology. Int. J. Med. Sci. 10, 206 (2013)

    Article  Google Scholar 

  13. Song, H.J., Lim, H.Y., Chun, W., Choi, K.C., Lee, T.-Y., Sung, J.H., et al.: Development of 3D skin-equivalent in a pump-less microfluidic chip. J. Ind. Eng. Chem. 60, 355–359 (2018)

    Article  CAS  Google Scholar 

  14. Abaci, H.E., Gledhill, K., Guo, Z., Christiano, A.M., Shuler, M.L.: Pumpless microfluidic platform for drug testing on human skin equivalents. Lab Chip 15, 882–888 (2015)

    Article  CAS  Google Scholar 

  15. Reijnders, C.M., van Lier, A., Roffel, S., Kramer, D., Scheper, R.J., Gibbs, S.: Development of a full-thickness human skin equivalent in vitro model derived from TERT-immortalized keratinocytes and fibroblasts. Tissue Eng. Part A 21, 2448–2459 (2015)

    Article  CAS  Google Scholar 

  16. Murphy, S.V., Atala, A.: 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773–785 (2014)

    Article  CAS  Google Scholar 

  17. Koch, L., Deiwick, A., Schlie, S., Michael, S., Gruene, M., Coger, V., et al.: Skin tissue generation by laser cell printing. Biotechnol. Bioeng. 109, 1855–1863 (2012)

    Article  CAS  Google Scholar 

  18. Fatehullah, A., Tan, S.H., Barker, N.: Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246–254 (2016)

    Article  Google Scholar 

  19. Kim, K., Kim, H., Sung, G.Y.: An Interleukin-4 and interleukin-13 induced atopic dermatitis human skin equivalent model by a skin-on-a-chip. Int. J. Mol. Sci. 23, 2116 (2022)

    Article  CAS  Google Scholar 

  20. Kim, K., Kim, J., Kim, H., Sung, G.Y.: Effect of α-lipoic acid on the development of human skin equivalents using a pumpless skin-on-a-chip model. Int. J. Mol. Sci. 22, 2160 (2021)

    Article  CAS  Google Scholar 

  21. Kim, K., Jeon, H.M., Choi, K.C., Sung, G.Y.: Testing the effectiveness of curcuma longa leaf extract on a skin equivalent using a pumpless skin-on-a-chip model. Int. J. Mol. Sci. 21, 3898 (2020)

    Article  CAS  Google Scholar 

  22. Sung, J.H., Wang, Y., Shuler, M.L.: Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems (MPS). APL bioengineering. 3, 021501 (2019)

    Article  Google Scholar 

  23. Harshad, K., Jun, M., Park, S., Barton, M.J., Vadivelu, R.K., St, J.J., et al.: An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells. Biomed. Microdevice 18, 1–10 (2016)

    Article  Google Scholar 

  24. Lü, D., Liu, X., Gao, Y., Huo, B., Kang, Y., Chen, J., et al.: Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model. PLoS ONE 8, e74563 (2013)

    Article  Google Scholar 

  25. Mihic, A., Li, J., Miyagi, Y., Gagliardi, M., Li, S.-H., Zu, J., et al.: The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials 35, 2798–2808 (2014)

    Article  CAS  Google Scholar 

  26. Mori, N., Morimoto Y., Takeuchi S. (2015) Skin-equivalent integrated with perfusable channels on curved surface. 2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS) IEEE, 351–353

  27. Mori, N., Morimoto Y., Takeuchi S. (2016) Stretchable culture device of skin-equivalent with improved epidermis thickness. 2016 IEEE 29th International Conference on Micro Electro Mechanical Systems (MEMS) IEEE, 259–262

  28. Jeong, S., Kim, J., Jeon, H.M., Kim, K., Sung, G.Y.: Development of an aged full-thickness skin model using flexible skin-on-a-chip subjected to mechanical stimulus reflecting the circadian rhythm. Int. J. Mol. Sci. 22, 12788 (2021)

    Article  CAS  Google Scholar 

  29. Gekakis, N., Staknis, D., Nguyen, H.B., Davis, F.C., Wilsbacher, L.D., King, D.P., et al.: Role of the CLOCK protein in the mammalian circadian mechanism. Science 280, 1564–1569 (1998)

    Article  CAS  Google Scholar 

  30. Brown, S.A., Fleury-Olela, F., Nagoshi, E., Hauser, C., Juge, C., Meier, C.A., et al.: The period length of fibroblast circadian gene expression varies widely among human individuals. PLoS Biol. 3, e338 (2005)

    Article  Google Scholar 

  31. Spörl, F., Schellenberg, K., Blatt, T., Wenck, H., Wittern, K.-P., Schrader, A., et al.: A circadian clock in HaCaT keratinocytes. J. Investig. Dermatol. 131, 338–348 (2011)

    Article  Google Scholar 

  32. Lim, H.Y., Kim, J., Song, H.J., Kim, K., Choi, K.C., Park, S., et al.: Development of wrinkled skin-on-a-chip (WSOC) by cyclic uniaxial stretching. J. Ind. Eng. Chem. 68, 238–245 (2018)

    Article  CAS  Google Scholar 

  33. Grinnell, F., Ho, C.-H., Lin, Y.-C., Skuta, G.: Differences in the regulation of fibroblast contraction of floating versus stressed collagen matrices. J. Biol. Chem. 274, 918–923 (1999)

    Article  CAS  Google Scholar 

  34. Grinnell, F.: Fibroblast–collagen-matrix contraction: growth-factor signalling and mechanical loading. Trends Cell Biol. 10, 362–365 (2000)

    Article  CAS  Google Scholar 

  35. Han, Y.L., Ronceray, P., Xu, G., Malandrino, A., Kamm, R.D., Lenz, M., et al.: Cell contraction induces long-ranged stress stiffening in the extracellular matrix. Proc. Natl. Acad. Sci. 115, 4075–4080 (2018)

    Article  CAS  Google Scholar 

  36. Ramtani, S.: Mechanical modelling of cell/ECM and cell/cell interactions during the contraction of a fibroblast-populated collagen microsphere: theory and model simulation. J. Biomech. 37, 1709–1718 (2004)

    Article  CAS  Google Scholar 

  37. Chipev, C.C., Simon, M.: Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and TGFβ1. BMC Dermatol. 2, 1–13 (2002)

    Article  Google Scholar 

  38. Sriram, G., Bigliardi, P.L., Bigliardi-Qi, M.: Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur. J. Cell Biol. 94, 483–512 (2015)

    Article  CAS  Google Scholar 

  39. Sand, J., Genovese F., Karsdal M. (2016) Type IV collagen. Biochemistry of Collagens, Laminins and Elastin. pp. 31–41. Elsevier

  40. Kaur, J., Reinhardt D.P. (2015) Extracellular matrix (ECM) molecules. stem cell biology and tissue engineering in dental sciences. pp. 25–45. Elsevier

  41. Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., et al.: Global quantification of mammalian gene expression control. Nature 473, 337–342 (2011)

    Article  Google Scholar 

  42. Mondrinos, M.J., Alisafaei F., Yi A.Y., Ahmadzadeh H., Lee I., Blundell C., et al. (2021) Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue. Science Advances. 7 eabe9446

  43. Huh, D., Mondrinos M., Blundell C., Seo J. (2021) Systems and methods for immobilizing extracellular matrix material on organ on chip, multilayer microfluidics microdevices, and three-dimensional cell culture systems. Google Patents

  44. Puccinelli, T.J., Bertics, P.J., Masters, K.S.: Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation. Acta Biomater. 6, 3415–3425 (2010)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the national Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (NRF-2020R1A2C2009928), Republic of Korea, and the Technology Innovation Program (or Industrial Strategic Technology Development Program-3D Organ-on-a-Chip-Based new Drug Development Platform Construction Project) (20008414, Development of intestine–liver–kidney multiorgan tissue chip mimicking absorption, distribution, metabolism, excretion of drug) funded By the Ministry of Trade, Industry and Energy(MOTIE, Korea).

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Authors and Affiliations

  1. Interdisciplinary Program of Nano-Medical Device Engineering, Hallym University, Chuncheon, 24252, Republic of Korea

    Kyunghee Kim, Subin Jeong & Gun Yong Sung

  2. Integrative Materials Research Institute, Hallym University, Chuncheon, 24252, Republic of Korea

    Kyunghee Kim, Subin Jeong & Gun Yong Sung

  3. Major in Materials Science and Engineering, Hallym University, Chuncheon, 24252, Republic of Korea

    Gun Yong Sung

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  1. Kyunghee Kim
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Correspondence to Gun Yong Sung.

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Kim, K., Jeong, S. & Sung, G.Y. Effect of Periodical Tensile Stimulation on the Human Skin Equivalents by Magnetic Stretching Skin-on-a-Chip (MSSC). BioChip J 16, 501–514 (2022). https://doi.org/10.1007/s13206-022-00092-x

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