Relationships between tissue dilatation and differentiation in distraction osteogenesis

Abstract

Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice‐modeling approach

“…Both models described tissue regeneration in the chamber qualitatively, but more qualitative and quantitative experimental results are necessary to corroborate the predictive capacities of the models. Although these theories predicted some of the main aspects of tissue regeneration in fracture healing, 5,7-9 tissue engineering, 10,11 bone/implant interfaces, 6,12,13 or distraction osteogenesis, [14][15][16][17] they may be criticized for this lack of corroboration.…”

Mechanobiological Models for Bone Tissue. Applications to Implant Design

“…The studies of Carter et al [84] were the first to use finite element models to explore the relationship between local stress/strain distribution and differentiated tissue types, and thus the first to quantify the level of mechanical stimulus. This theory has been used to study fracture healing [84,85] and distraction osteogenesis [86].…”

Bone regeneration during distraction osteogenesis

“…Active distraction creates pressure, fl uid fl ow, tensile strain, and tissue dilatation (local deformation occurring equally in all directions) within and around the distraction area. 41,45,46 A computational study has suggested that tissue within the distraction gap experiences a transient increase of pressure and fl uid fl ow for up to 20 min after each distraction cycle and undergoes near-static tensile stretch and tissue dilatation between one distraction cycle and the next. 46 These mechanical stimuli cause changes at the cellular and molecular level and infl uence the proliferation and the differentiation of multipotent mesenchymal cells.…”

“…41,45,46 A computational study has suggested that tissue within the distraction gap experiences a transient increase of pressure and fl uid fl ow for up to 20 min after each distraction cycle and undergoes near-static tensile stretch and tissue dilatation between one distraction cycle and the next. 46 These mechanical stimuli cause changes at the cellular and molecular level and infl uence the proliferation and the differentiation of multipotent mesenchymal cells. [17][18][19][20][21][22][23] Studies have demonstrated during the different phases of distraction osteogenesis an increased expression of the various cytokines involved in the regulation of bone synthesis and turnover.…”