Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for three-dimensional bone tissue engineering

Wich Orapiriyakul, Monica P. Tsimbouri, Peter G. Childs, Paul Campsie, Julia Wells, Marc A. Fernandez-Yague, Karl Burgess, K. Elizabeth Tanner, Manlio Tassieri, Dominic Meek, Massimo Vassalli, Manus J. P. Biggs, Manuel Salmerón-Sánchez, Richard O. C. Oreffo, Stuart Reid, Matthew J. Dalby

Research output: Contribution to journalArticle

1 Downloads (Pure)

Abstract

There is a pressing clinical need to develop cell-based bone therapies due to a lack of viable, autologous bone grafts and a growing demand for bone grafts in musculoskeletal surgery. Such therapies can be tissue engineered and cellular, such as osteoblasts, combined with a material scaffold. Because mesenchymal stem cells (MSCs) are both available and fast growing compared to mature osteoblasts, therapies that utilize these progenitor cells are particularly promising. We have developed a nanovibrational bioreactor that can convert MSCs into bone-forming osteoblasts in two- and three-dimensional, but the mechanisms involved in this osteoinduction process remain unclear. Here, to elucidate this mechanism, we use increasing vibrational amplitude, from 30 nm (N30) to 90 nm (N90) amplitudes at 1000 Hz and assess MSC metabolite, gene, and protein changes. These approaches reveal that dose-dependent changes occur in MSCs' responses to increased vibrational amplitude, particularly in adhesion and mechanosensitive ion channel expression and that energetic metabolic pathways are activated, leading to low-level reactive oxygen species (ROS) production and to low-level inflammation as well as to ROS- and inflammation-balancing pathways. These events are analogous to those that occur in the natural bone-healing processes. We have also developed a tissue engineered MSC-laden scaffold designed using cells' mechanical memory, driven by the stronger N90 stimulation. These mechanistic insights and cell-scaffold design are underpinned by a process that is free of inductive chemicals.

Original languageEnglish
Pages (from-to)10027-10044
Number of pages18
JournalACS Nano
Volume14
Issue number8
Early online date23 Jul 2020
DOIs
Publication statusPublished - 25 Aug 2020

Keywords

  • mesenchymal stem cells
  • nanovibration
  • mechanotransduction
  • bioreactor
  • bone tissue engineering

Fingerprint Dive into the research topics of 'Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for three-dimensional bone tissue engineering'. Together they form a unique fingerprint.

  • Cite this

    Orapiriyakul, W., Tsimbouri, M. P., Childs, P. G., Campsie, P., Wells, J., Fernandez-Yague, M. A., Burgess, K., Tanner, K. E., Tassieri, M., Meek, D., Vassalli, M., Biggs, M. J. P., Salmerón-Sánchez, M., Oreffo, R. O. C., Reid, S., & Dalby, M. J. (2020). Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for three-dimensional bone tissue engineering. ACS Nano, 14(8), 10027-10044. https://doi.org/10.1021/acsnano.0c03130