Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals

Abstract

Purpose of review: Connecting organ-scale loads to cellular signals in their local in vivo environment is a current challenge in the field of bone (re)modelling. Understanding this critical missing link would greatly improve our ability to anticipate mechanotransduction during different modes of stimuli and the resultant cellular responses. This review characterises computational approaches that could enable coupling links across the multiple scales of bone.

Recent findings: Current approaches using strain and fluid shear stress concepts have begun to link organ-scale loads to cellular signals; however, these approaches fail to capture localised micro-structural heterogeneities. Furthermore, models that incorporate downstream communication from osteocytes to osteoclasts, bone-lining cells and osteoblasts, will help improve the understanding of (re)modelling activities. Incorporating this potentially key information in the local in vivo environment will aid in developing multiscale models of mechanotransduction that can predict or help describe resultant biological events related to bone (re)modelling. Progress towards multiscale determination of the cell mechanical environment from organ-scale loads remains elusive. Construction of organ-, tissue- and cell-scale computational models that include localised environmental variation, strain amplification and intercellular communication mechanisms will ultimately help couple the hierarchal levels of bone.

Keywords: Bone (re)modelling; Computational systems biomechanics; Local in vivo environment; Mechanical stimulation; Osteocytes.

Figure 1. Capturing the mechanical environment over different scales has been performed using many approaches.

(a) Organ scale, (b) Tissue scale, (c) Cell scale, and (d) Molecular scale (69) have been captured by (a1 – c2). Micro-FE models such as (a1) Schulte et al. (63) and (b1) Lambers et al. (61) have been applied at organ level to calculate the tissue level mechanical environment. Within the tissue level, localised tissue boundary conditions can be used to calculate a reduced tissue scale bone marrow environment, such as (b2) investigated by Metzger et al. (71). The RVE (c1) concept can be applied to link organ-scale loads to a BMU type environment such as that by Lerebours et al. (52) Boundary conditions from the lower end of the tissue scale can be applied to determine fluid flow stresses on the cell, as seen by Vaughan et al. (43) in (c2). In the molecular scale, stretch, primary cilia deformation and signalling between osteocytes and other mechanosensitive cells can be simulated; an example of this is the model by Jahani et al. (80) studying the osteocyte – bone lining cell signalling pathways (d1). a1 reproduced in adherence with the CC BY licence applied by PLOS One, b1, b2, d1 reproduced with permission from Elsevier and c1,c2, d reproduced with permission from Springer.