Mechanical Modulation of Fracture Healing and Implications for Skeletal Tissue Engineering - Engineered Bone: Tissue Engineering Intelligence Unit - page 75

The characteristics of an osteogenic mechanical stimulus are cyclical deformation rather
than static loads, high rates of deformation, and diverse strain distributions. Recently the use of
low magnitude strain at a specific frequency has been shown to be osteogenic, particularly in
cancellous bone and in stimulating bone ingrowth into implants. 73 An interesting mediator of
the mechano transduction pathway has been identified as the estrogen receptor. 12,21,22,23
In the event of a decrease in loading bone mass is reduced. This is seen throughout the
skeleton with bed rest and long term space flight. However, although there is a loss of bone
throughout the level of loss is not uniform. Long term space flight induces a greater loss of
bone mass from the lower limbs and in particular the distal bones of the lower limb. In the
calcaneus some 5-10% of bone can be lost. Interestingly it appears that this loss can be modu-
lated using short daily periods of mechanical stimulation based upon the heel strike transient,
namely a high rate deformation. 32 Thus, these adaptive responses can be localized to regions of
the skeleton or even a site within a single bone. This is particularly seen adjacent to joint
replacement prostheses, where bone loss occurs at sites protected from normal functional strains
by load sharing with the prosthetic component. 49
This ability of the skeleton to adapt to changes in loading is very relevant to bone repair.
The degree of injury resulting in fracture together with the fixation of the fracture both con-
tribute to a reduction in the loading of the affected limb. Thus the normal mechanical environ-
ment for osteogenesis is changed to a scenario of reduced loading, associated with a drive to
reduce bone mass. However, although there is indeed a loss of bone mass in the affected limb,
the fractured bone does also undergo a repair process which involves bone formation. Thus an
interesting paradox of reduced load and a simultaneous requirement for increased bone forma-
tion arises. An understanding of the interactions of mechanical environment and bone forma-
tion can provide an ability to enhance the process of fracture repair.
The aspects of mechanical stimulation that induce an osteogenic response are summarised
as short periods of daily cyclical deformation, particularly at high strain rates and diverse strain
distributions. The recent finding that the osteogenic potential of low magnitude sub-physiological
strains at specific frequency, which can activate osteoblasts especially in cancellous bone, 73 was
similar to that advocated by Weinbaum et al, 1994, as important in the mediation of osteo-
genic activity by streaming potentials. Streaming potentials are induced as a consequence of
ionic fluid movement across a charged surface when bone is deformed. The role of streaming
potentials as part of the strain related bone adaptation transduction mechanism has been ex-
plored by a number of authors 52,63,82 The mechanical characteristics that act to stimulate os-
teogenic activity in intact bone are also useful in the modulation of bone repair.
Fracture and Modes of Mechanical Failure
Bone may fracture as a consequence of a single episode of monotonic overload resulting in
catastrophic fracture, or by fatigue failure from accumulation of micro-damage within the
matrix associated with cyclical loading over a time period inadequate for an adaptive response.
Rapid cyclical loading of bone matrix over a short time period can induce fatigue damage
within the matrix. This micro-damage, seen as micro-cracks within the matrix 3,57,85 may occur
throughout life and is normally repaired by the process of intra-cortical secondary osteonal
remodelling. The presence of micro-damage is accompanied by an increase in osteocyte apoptosis
and the activation of osteoclastic resorption followed by osteoblasts forming concentric lamel-
lae and a secondary osteon. An increased number of loading cycles over a short period of time,
as is seen for example in some training protocols, can lead to accumulation of micro-damage at
a rate greater than that of the repair process resulting in a painful condition. This scenario may
be seen in ballet dancers, army recruits and racehorses in training. 61,62 Persistent loading can
cause micro-cracks which can coalesce and result in a gross fracture of the affected bone.
Fracture can also occur under normal physiological loading conditions where bone strength
is compromised. Such fractures occur in the elderly, particularly post-menopausal women with
low bone mass. Specific sites of the skeleton are predilection sites for such fractures; these