In vitro models for bone mechanobiology: Applications in bone regeneration and tissue engineering

Abstract

Healthy bone healing is a remarkable, mechanically sensitive, scar-free process that leads rapidly to repair tissue of high mechanical quality and functionality, and knowledge of this process is essential for driving advances in bone tissue engineering and regeneration. Gaining this knowledge requires the use of models to probe and understand the detailed mechanisms of healing, and the tight coupling of biology and mechanics make it essential that both of these aspects are controlled and analysed together, using a mechanobiological approach. This article reviews the literature on in vitro models used for this purpose, beginning with two-dimensional (2D) cell culture models used for applying controlled mechanical stimuli to relevant cells, and detailing the analysis techniques required for understanding both substrate strain and fluid flow stimuli in sufficient detail to relate them to biological response. The additional complexity of three-dimensional (3D) models, enabling more faithful representation of the healing situation, can require correspondingly more sophisticated tools for mechanical and biological analysis, but has recently uncovered exciting evidence for the mechanical sensitivity of angiogenesis, essential for successful healing. Studies using explanted tissue continue to be vital in informing these approaches, providing additional evidence for the relevance of effects in biological and mechanical environments close to those in the living organism. Mechanobiology is essential for the proper analysis of models for bone regeneration, and has an exciting integrative role to play not only in advancing knowledge in this area, but also in ensuring successful translation of new tissue engineering and regenerative therapies to the clinic.

Quantification of fluid shear stress in bone tissue engineering scaffolds with spherical and cubical pore architectures

“…This is facilitated through the use of highly porous scaffold architectures, which enable nutrient and metabolite diffusion throughout, while also contributing to the shape and mechanical integrity of the tissue defect. Mechanical stimulation, in the form of fluid perfusion and mechanical compression, have been shown to play an important role in enhancing tissue regeneration and also directing the cellular fate of mesenchymal stem cells (MSCs) (Angele et al 2004;Delaine-Smith and Reilly 2012;Jaasma and O'Brien 2008;Keogh et al 2011;Liu et al 2012b;Miyashita et al 2014; Thompson et al 2010). For example, osteogenic differentiation of MSCs is prompted under mechanical stimulation, as indicated by the increase of Alkaline Phosphatase (ALP), Prostaglandin E 2 (PGE 2 ) expression and mineralisation (Bancroft et al 2002;Grayson et al 2008;Vance et al 2005;Yu et al 2004).…”

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

“…Recent studies have shown that mechanical stimulation enhances bone tissue regeneration in vitro to a certain extent (Sittichockechaiwut et al 2009;Jaasma et al 2008;Goldstein et al 2001). In particular, it has been shown that osteogenic differentiation, as indicated by ALP, COX 2 and PGE 2 expression (Thompson et al 2010;Keogh et al 2011;Liu et al 2012), is enhanced when bone cells are exposed to the fluid flow, compared to static culture (Jaasma et al 2008;Goldstein et al 2001;Li et al 2009). Such changes could be related to the enhanced nutrient transport or mechanical stimulation of the cells within the scaffolds, but the precise nature of such changes is not yet known.…”

A new intramedullary sustained dynamic compression nail for the treatment of long bone fractures: a biomechanical study

“…[39][40][41] Under compressive loading 400 to 2,465 μ-strain was recorded at the synthetic bone fracture site with SDCN. This value is consistent with the literature data.…”