Mechanical Modulation of Fracture Healing and Implications for Skeletal Tissue Engineering - Engineered Bone: Tissue Engineering Intelligence Unit - page 83

The increased progression of healing of an appropriate level of initial deformation applied
as a cyclical mechanical stimulus can be enhanced further by reducing the magnitude of the
displacement as a function of time. This subtle programming of the mechanical input signifi-
cantly improved the progression of healing in the ovine tibial osteotomy model. 18
This type of stimulus mimics the normal reduction in inter-fragmentary displacement that
occurs in normal healing and may stimulate tissue differentiation through a mechanobiologically
mediated pathway. The reduction in inter-fragmentary motion could be attributed to the in-
creased material stiffness of the different tissues present in the differentiation cascade; any
adverse loading that damages these tissues would inhibit the cascade and delay differentiation.
Alternatively the reduction in motion may be mediated by other mechanisms, possible
mechanosensory pathways, and the consequence of the reduced motion drives the tissue differ-
entiation. Thus the active time related reduction in displacement 18 demonstrated that this
additional refinement to the healing environment did have a further significant effect.
These studies using in vivo models have demonstrated the extreme sensitivity of the process
of bone healing in response to local mechanical environment, and the potential for individual
control and monitoring through appropriate fixation systems.
The Time of Application of Imposed Mechanical Stimulation
The critical period for assuring rapid progression of fracture healing is in the early stages of
the repair process. Delay in providing the correct environment for healing can lead to a delay or
even failure of the process to occur at all, resulting in a nonunion (McKibbin, personal com-
munication).
Although some regimens of applied micro-movement have been shown to enhance the rate
of repair in osteotomy models, when applied at a later stage of healing these regimens can
adversely affect the progression of healing. The regimen of a high displacement rate applied at
the onset of healing significantly increased the rate of both mineralisation and fracture stiffness
index. However, if the same regimen was applied at the time of callus bridging, the effect was to
inhibit the progression of healing. The stimulus was only applied for approximately 17 min-
utes per day, thus healing can be adversely affected by changes in mechanical environment
during the period of repair and these changes may only be for a short time. 32
The study by Lawes et al (1996), 32a in which fixators of two differing levels of compliance
were used, showed the difference between the two groups in terms of inter-fragmentary dis-
placement was seen only in the early stages of the repair process. By six weeks post-osteotomy
levels of inter-fragmentary displacement were similar in each group and remained so declining
in both groups to the end of the healing period. However, the progression and outcome of
healing were significantly greater in the groups with the low compliance fixator, which induced
a greater magnitude of inter-fragmentary displacement in the very early stages of repair. This
also provides evidence that stimulation in the early stages of healing could enhance the process.
Indeed this was confirmatory of a trial in human patients by Kershaw et al (1993) 44 in which
the magnitude of inter-fragmentary motion was determined in the early stages of healing and
found to be in the order of 0.6mm, this was increased by 50% using an externally attached
actuator. A significant reduction in healing time was obtained in a prospective trial using
micromotion applied in the early stages of the healing process.
In an ovine experimental study with a 3 mm tibial osteotomy Hente et al (1999), 39 were
unable to show an effect of axial dynamisation. However, in this study the dynamisation was
not applied until the fourth week post osteotomy, thus the lack of modulation of the repair
process could be a consequence of missing the early phase of healing or alternatively an inap-
propriate dynamisation regimen. As stated previously the characteristics of any applied me-
chanical stimulus will influence the type of modulation compared to the nonstimulated pat-
tern of repair.