TY - JOUR
T1 - Nanovibrational stimulation of mesenchymal stem cells induces therapeutic reactive oxygen species and inflammation for three-dimensional bone tissue engineering
AU - Orapiriyakul, Wich
AU - Tsimbouri, Monica P.
AU - Childs, Peter
AU - Campsie, Paul
AU - Wells, Julia
AU - Fernandez-Yague, Marc A.
AU - Burgess, Karl
AU - Tanner, K. Elizabeth
AU - Tassieri, Manlio
AU - Meek, Dominic
AU - Vassalli, Massimo
AU - Biggs, Manus J. P.
AU - Salmerón-Sánchez, Manuel
AU - Oreffo, Richard O. C.
AU - Reid, Stuart
AU - Dalby, Matthew J.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - 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.
AB - 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.
KW - mesenchymal stem cells
KW - nanovibration
KW - mechanotransduction
KW - bioreactor
KW - bone tissue engineering
U2 - 10.1021/acsnano.0c03130
DO - 10.1021/acsnano.0c03130
M3 - Article
SN - 1936-0851
VL - 14
SP - 10027
EP - 10044
JO - ACS Nano
JF - ACS Nano
IS - 8
ER -