Mechanobiology of Bone - Engineered Bone: Tissue Engineering Intelligence Unit - page 36

Figure 5. Fluid flow pattern in a remodeling osteon at maximum load during a walking cycle. Volumetric
expansion leads to influx of canalicular fluid at the tip of the cone. At the base of the cone, high volumetric
compression produces high efflux of canalicular fluid. Figure taken from Burger et al, 2002, with permis-
sion.
the soft callus tissue. In the callus a mix of cell types is present, fibroblast-like cells, osteoblasts
and chondrocytes. 36 Fibroblasts as well as bone cells and chondrocytes have been shown to be
mechano-sensitive, although the responses depend on cell-type. Responses to strain include
synthesis of growth factors, cytokines and hormones, 93,114,115 changes in matrix synthe-
sis, 41,42,45,95 and cell alignment. 44,45,90 Tensile forces have been shown to stimulate differentia-
tion of mesenchymal cells towards a fibroblastic phenotype. 45 Hence, mechanical stimuli affect
the preferential differentiation towards certain tissue types and may play an important role in
the control of tissue development. Pauwels 116 suggested preferential differentiation of tissue to
occur on the basis of the amount and type of mechanical deformation. This idea has been
refined further and translated into quantitative models. 117-119 Based on the assumption that
cells differentiate into various phenotypes in response to biophysical stimuli, the models suc-
cessfully predict patterns of fracture healing. 118,119 These theoretical models confirmed the
feasibility of mechanical controlled tissue differentiation. Several experimental findings also
support this hypothesis. For instance, a relationship between mechanical loading and BMP
expression was found in vivo. 34,120,121 BMPs are thought to be involved in controlling the
differentiation of cartilage and bone. In addition, Sato et al 122 found that the expression of the
mRNA for various bone matrix proteins was stimulated by distraction of the callus and that
mechanical tension-stress modulated cell shape and phenotype.
The mechanical context not only affects tissue growth and differentiation, but also forms
the boundary conditions in which various tissue types can thrive. Too large strains, for in-
stance, inhibit or even prevent ossification 35,37,123 and even larger strains are also deleterious
for fibrous tissue. 40 High strains applied to osteoblasts or fibroblasts in culture cause them to
align away from the principal strain direction, 44,124 indicating that they try to avoid these large
deformations. The exact load on the cells is not known because of the complex viscoelastic
nature of the tissue. The magnitude and distribution of strain over the distraction area depend
on several factors, which change over time. These factors include the relative stiffness of the
local tissue, the distraction rate, the stiffness of the fixator and the amount of loading. If areas
within the soft tissue are sufficiently stable, whether by modulated tissue stiffness or due to
external conditions, ossification occurs.
Mechanical Stimuli and Bone Engineering
We have argued that adaptive bone remodeling and osteogenesis are two distinct processes.
Osteocytes are believed to play a role as mechanosensors in adult bone. In fracture healing and
DOG new bone is formed via a cascade of events, akin to embryonic bone development, which