Skeletal regeneration is accomplished by a cascade of biologic process
es that may include differentiation of pluripotential tissue, endochon
dral ossification, and bone remodeling. It has been shown that all the
se processes are influenced strongly by the local tissue mechanical lo
ading history. This article reviews some of the mechanobiologic princi
ples that are thought to guide the differentiation of mesenchymal tiss
ue into bone, cartilage, or fibrous tissue during the initial phase of
regeneration. Cyclic motion and the associated shear stresses cause c
ell proliferation and the production of a large callus in the early ph
ases of fracture healing. For intermittently imposed loading in the re
generating tissue: (1) direct intramembranous bone formation is permit
ted in areas of low stress and strain; (2) low to moderate magnitudes
of tensile strain and hydrostatic tensile stress may stimulate intrame
mbranous ossification; (3) poor vascularity can promote chondrogenesis
in an otherwise osteogenic environment; (4) hydrostatic compressive s
tress is a stimulus for chondrogenesis; (5) high tensile strain is a s
timulus for the net production of fibrous tissue; and (6) tensile stra
in with a superimposed hydrostatic compressive stress will stimulate t
he development of fibrocartilage, Finite element models are used to sh
ow that the patterns of tissue differentiation observed in fracture he
aling and distraction osteogenesis can be predicted from these fundame
ntal mechanobiologic concepts. In areas of cartilage formation, subseq
uent endochondral ossification normally will proceed, but it can be in
hibited by intermittent hydrostatic compressive stress and accelerated
by octahedral shear stress (or strain). Later, bone remodeling at the
se sites can be expected to follow the same mechanobiologic adaptation
rules as normal bone.