Mechanobiology of Bone - Engineered Bone: Tissue Engineering Intelligence Unit - page 28

C HAPTER 4

Mechanobiology of Bone

Elisabeth H. Burger, Jenneke Klein-Nulend and Margriet Mullender

Abstract

Mechanical force is an important regulator of bone formation and resorption. Bone

tissue remains adapted to the magnitude and direction of its daily loadings through-
out life, as a result of continuous adaptive remodeling. In culture, bone cells demon-
strate a high responsiveness to mechanical strain, both resulting from fluid shear stress and
from cell stretching, but the type of response seems to differ: fluid shear stress causes the rapid
production of nitric oxide and prostaglandins, while cell stretching leads to cell alignment and
cell proliferation. Fluid shear stress occurs in the osteocyte canaliculi during dynamic loading
of intact bone, while cell stretching occurs a.o. in osteogenic soft tissue during distraction
osteogenesis. Here we discuss the concept that the response to fluid shear stress in vitro reflects
mechanotransduction by osteocytes in intact remodeling bone. The response to cell stretching
however may reflect the osteogenic response to stretching of soft tissue as occurs in distraction
osteogenesis. In tissue engineering, both stimuli offer possibilities for enhancing bone cell growth
in vitro.

Introduction
An important issue in Bone Tissue Engineering is the phenomenon of mechanical adapta-
tion, also called Wolff 's Law. 1,2 Mechanical adaptation of bone tissue means that not only the
form of a whole bone but also it's internal structure is adapted to the magnitude and direction
of the forces acting upon it during daily movement of the body. At the tissue level, mechanical
adaptation is the cellular process whereby living bone adapts it's mass and structure to prevail-
ing loads to obtain a higher efficiency of load bearing. Adaptation will improve an individual's
survival chance, because bone is not only hard, but also heavy. Too much of it is probably as
bad as too little, as it leads either to uneconomic energy consumption during movement (when
bone mass is too high) or to an enhanced fracture risk (when bone mass is too low). This easily
explains the usefulness of mechanical adaptation, even if we do not know the cellular mecha-
nism by which it is obtained. Adaptation continues throughout life, also when bone tissue is
renewed, as is necessary for most tissues in the body. Renewal occurs by resorption of old bone
and formation of new bone in a process called remodeling. 3 Changes in the magnitude and
direction of loads are followed by changes in both mass and orientation of the bony tissue, as
originally shown by Wolff, 1 and in modern medicine by the loss of alveolar bone from the
edentulous jaw and the growth of bone around hip implants. 4 Maintenance of an adapted
structure during remodeling means that the daily loads to which the bone is subjected some-
how regulate the activities of the cells involved in remodeling. The question is how this regula-
tion occurs.
A completely different case of mechanical regulation of bone tissue formation is distraction
osteogenesis (DOG), a method applied in orthopedic and oral surgery to lengthen bones. In
DOG, force is applied by mechanically separating the two bony walls of an osteotomy, after
the gap has filled with osteogenic connective tissue. 5 This collagenous connective tissue that