Perspectives on in silico bone mechanobio

Abstract

Bone mechanobiology is the study of the physical, biological and mechanical processes that continuously affect the multiscale multicellular system of the bone from the organ to the molecular scale. Current knowledge derives from experimental studies, which are often limited to gathering qualitative data in a cross-sectional manner, up to a restricted number of time points. Moreover, the simultaneous collection of information about 3D bone microarchitecture, cell activity as well as protein distribution and level is still a challenge. In silico models can expand qualitative information with hypothetical quantitative systems, which allow quantification, testing and comparison to existing quantifiable experimental data. An overview of multiscale, multiphysics, agent-based and hybrid techniques and their applications to bone mechanobiology is provided in the present review. The study analysed how mechanical signals, cells and proteins can be modelled in silico to represent bone remodelling and adaptation. Hybrid modelling of bone mechanobiology could combine the methods used in multiscale, multiphysics and agent-based models into a single model, leading to a unified and comprehensive understanding of bone mechanobiology. Numerical simulations of in vivo multicellular systems aided in hypothesis testing of such in silico models. Recently, in silico trials have been used to illustrate the mechanobiology of cells and signalling pathways in clinical biopsies and animal bones, including the effects of drugs on single cells and signalling pathways up to the organ level. This improved understanding may lead to the identification of novel therapies for degenerative diseases such as osteoporosis.

Trabecular bone remodeling in the ageing mouse: a micro-multiphysics agent-basedin silicomodel using single-cell mechanomics

“…cancellous, cortical and marrow tissues) across many spatial and temporal scales. Hybrid modeling has been identified as a powerful modeling technique which combines multiscale, multiphysics, and agent-based modeling to analyze in a unified way the organ, tissue, cell, and gene scales over weeks, months or even years (Boaretti et al 2022). Such an in silico model can deal with the action of single cells while millions of cells are active and interact with each other in a multiscale simulation, making this tool ideal to explore the hierarchical processes governing bone mechanobiology.…”

“…We have recently proposed an in silico multiscale micro-multiphysics agent-based (micro-MPA) model (Boaretti et al 2018) adapted from the model of fracture healing in cortical bone by Tourolle (2019). This micro-MPA model was based on multiscale (from the organ to the protein spatial scales and from weeks to minutes as temporal scales), multiphysics (mechanical signal, reaction-diffusiondecay of cytokines), and agent-based modeling (single-cell behavior).…”

Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-based in silico model using single-cell mechanomics

“…It is known that bone remodeling is regulated by the interaction between different cells and tissues (i.e., cancellous, cortical and marrow tissues) across many spatial and temporal scales. Hybrid modeling has been identified as a powerful modeling technique which combines multiscale, multiphysics, and agent-based modeling to analyze in a unified way the organ, tissue, cell, and gene scales over weeks, months or even years (Boaretti et al, 2022). Such an in silico model can deal with the action of single cells while millions of cells are active and interact with each other in a multiscale simulation, making this tool ideal to explore the hierarchical processes governing bone mechanobiology.…”

“…We have recently proposed an in silico multiscale micromultiphysics agent-based (micro-MPA) model (Boaretti et al, 2018) adapted from the model of fracture healing in cortical bone by Tourolle (2019). This micro-MPA model was based on multiscale (from the organ to the protein spatial scales and from weeks to minutes as temporal scales), multiphysics (mechanical signal, reaction-diffusion-decay of cytokines), and agent-based modeling (single-cell behavior).…”