Mechanical Modulation of Fracture Healing and Implications for Skeletal Tissue Engineering - Engineered Bone: Tissue Engineering Intelligence Unit - page 72

C HAPTER 7

Mechanical Modulation of Fracture Healing
and Implications for Skeletal Tissue
Engineering

Allen Goodship

Abstract

This chapter addresses the factors involved in the functional adaption of intact bone and

the relevance of these to mechanical modulation of bone repair. The sensitivity of the
repair process to the overall mechanical conditions imposed by the fixation system used
is described. In addition the further modulation of the process of indirect bone repair by ap-
plication of dynamic inter-fragmentary micro-movement. The putative common mechano-
transduction pathways that may link functional adaptation in intact bone to the mechanical
modulation of indirect bone repair and the relevance of these in optimisation of fracture heal-
ing are presented.
The process of indirect bone repair involving a cascade of connective tissue differentiation is
discussed in relation to mechanical cues for selective specific tissue differentiation and the
computer modelling of this process. Finally bone repair is discussed in relation to new concepts
in skeletal tissue engineering and control of tissue responses in vivo.

Introduction
The mammalian skeleton provides structural support for the body, protection of some of
the vital organs and a reserve of minerals. However, the mechanical aspects of the skeleton are
paramount in enabling movement and locomotion with optimal energetic efficiency. The indi-
vidual skeletal elements form a series of specific bones, identifiable from their specific morpho-
logical characteristics. The formation of these elements arises from a combination of a geneti-
cally determined template and the ability to mount a response to mechanical cues arising from
the prevailing functional environment. Experimental evidence has been produced to demon-
strate the refinement of certain morphological features of the genetically determined form by
functional mechanical loading (Fig. 1) and the identification of morphological features deter-
mined by genetic influences and those arising from mechanical loading. 9,26
During the changing mechanical demands of development and growth and throughout
adult life the skeleton responds to mechanical input in a manner that optimises the functional
and energetic performance of the individual.
Bone may be considered as a tissue, a structure and an organ. At the tissue level it is classi-
fied as a connective tissue in that it comprises cell populations and a composite extra-cellular
matrix. This tissue is acutely sensitive to changes in mechanical environment in terms of mass
and architecture. The cell populations respond to mechanical signals in a coordinated manner
to optimise the distribution and mass of tissue within the structural skeletal elements to ac-
commodate the magnitude and distribution of loads experienced at any particular time. 80