Mechanical Modulation of Fracture Healing and Implications for Skeletal Tissue Engineering - Engineered Bone: Tissue Engineering Intelligence Unit - page 82

this short term low magnitude specific frequency inter-fragmentary stimulation was to en-
hance the progression of healing, particularly the formation of periosteal callus. This resulted
in a significantly greater torsional stiffness and strength compared to the non stimulated con-
trol. In this study the stimulus was delivered via the external fixator and the inter-fragmentary
displacement measured at the osteotomy site from accessory half pins. 31 In another study by
Wolff et al (2001), 31a using a ground vibration plate to induce 200 microns at 20 Hz no
significant effect was seen, although these authors did report 11% greater callus in the stimu-
lated group compared to controls.
Chen at al (1994) 11 used a rabbit model to evaluate the effects of different frequencies of
mechanical vibration on the repair of a fracture of the radius. They found that all vibration
stimuli enhanced repair compared to the nonstimulated control. The most effective of the
vibration frequencies was found to be 25 and 50 Hz.
This suggests a frequency dependent relationship with displacement magnitude, again re-
sembling the effects seen in intact bone. This type of stimulus would have advantages in stimu-
lation of a biological effect with minimal detriment to implants and the tissues occurring dur-
ing the process of endochondral bone repair as a consequence of the very low strain magnitudes
required.
The deformations applied at these specific frequencies were imposed as a sine wave. How-
ever, the early application of cyclical micromotion reported by Goodship and Kenwright (1985) 34
were applied using a ramped square wave, thus in both situations the rate of applied deforma-
tion was relatively high. In intact bone high strain rate is an important osteogenic mechanical
signal. Using the same ovine model the importance of high strain rate was shown by Goodship
et al (1998), 32 osteotomies stimulated with short periods of daily micromovement with a high
rate of deformation showing a statistically significant increase in the rate of mineralisation and
increase in fracture stiffness compared to both non stimulated controls and groups stimulated
with a low rate of deformation. The effect of rate of deformation may be related to the nature
of the healing callus, this being a heterogeneous mix of connective tissues, the nonosseus tissues
in particular exhibiting viscoelastic properties. The modulus of viscoelastic materials changes
as a function of strain rate. At high rates of deformation these materials exhibit a higher stiff-
ness, thus in the healing fracture it is possible that significant strains could be imposed on the
fracture fragments via the callus, whereas at lower rates of deformation the viscoelastic nature
of the callus would prevent such stimuli occurring on the fracture fragments. Thus at high rates
of deformation an osteogenic signal could be generated in the bone adjacent to the fracture.
The amount of deformation can be limited by the device stiffness in relation to the forces
applied either by the patient or by the stimulation system. The stage of tissue differentiation
will also control the level of inter-fragmentary displacement in relation to the applied force.
Thus if the applied force is high the strains may exceed the ultimate strain value for the differ-
entiating tissues and induce further damage. This may in turn lead to a delay or failure in
healing. Provided the inter-fragmentary displacements are imposed with a low force the callus
tissue differentiation will proceed from the fracture haematoma to lamellar bone.
As the tissues change during healing the material properties also change with an increase in
stiffness, thus the inter-fragmentary displacement decreases with time, whereas the loading of
the limb increased with time. Thus there is a complex control of loading of the healing fracture,
subsequent to the acute period where pain associated with inter-fragmentary motion will limit
the loading of the fracture. Experimental studies have also shown that even for very short
periods of daily stimulation the application of a high load to achieve inter-fragmentary dis-
placement can result in an inhibition to healing. 42 Goodman and Aspenberg (1993) 28 also
suggested the exogenous application of loads could provide a stimulus for bone healing and
ingrowth into porous materials by utilising the principles of Wolff 's observation as early as
1892 that bone was a dynamic material responsive to mechanical environment.