Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for 3D bone tissue engineering

Orapiriyakul, W. et al. (2020) Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for 3D bone tissue engineering. ACS Nano, 14(8), pp. 10027-10044. (doi: 10.1021/acsnano.0c03130) (PMID:32658450) (PMCID:PMC7458485)

[img]
Preview
Text
220500.pdf - Published Version
Available under License Creative Commons Attribution.

7MB

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 utilise these progenitor cells are particularly promising. We have developed a nanovibrational bioreactor that can convert MSCs into bone-forming osteoblasts in 2D and 3D 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 new mechanistic insights and cell-scaffold design are underpinned by a process that is free of inductive chemicals.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Salmeron-Sanchez, Professor Manuel and Burgess, Dr Karl and Orapiriyakul, Wich and Childs, Dr Peter and Dalby, Professor Matthew and Reid, Professor Stuart and Tsimbouri, Dr Monica and Campsie, Mr Paul and Tassieri, Dr Manlio and Vassalli, Dr Massimo and Tanner, Professor Kathleen
Authors: Orapiriyakul, W., Tsimbouri, M., Childs, P., Campsie, P., Wells, J., Fernandez-Yague, M. A., Burgess, K., Tanner, K. E., Tassieri, M., Meek, D., Vassalli, M., Biggs, M. J.P., Salmeron-Sanchez, M., Oreffo, R. O.C., Reid, S., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering > Biomedical Engineering
College of Science and Engineering > School of Engineering > Electronics and Nanoscale Engineering
College of Science and Engineering > School of Physics and Astronomy
Journal Name:ACS Nano
Publisher:American Chemical Society
ISSN:1936-0851
ISSN (Online):1936-086X
Published Online:13 July 2020
Copyright Holders:Copyright © 2020 American Chemical Society
First Published:First published in ACS Nano 14(8):10027–10044
Publisher Policy:Reproduced under a Creative Commons Licence

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173494Rapid Bone Graft Synthesis Through Dual Piezoelectric/Nanomechaniocal StimulationMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/P00220X/1Institute of Molecular, Cell & Systems Biology
305758Developing the nanokick bioreactor for commercialisation and cell therapyMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/S018808/1Institute of Molecular, Cell & Systems Biology
172525Developing the NanoKick bioreactor to enable tissue engineered bone graft and use of metabolomics to identify bone specific drug candidatesMatthew DalbyEngineering and Physical Sciences Research Council (EPSRC)EP/N013905/1Institute of Molecular, Cell & Systems Biology
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering