Angiogenesis and Mineralization During Distraction Osteogenesis

Abstract

Distraction osteogenesis is currently a standard method of bone lengthening. It is a viable method for the treatment of short extremities as well as extensive bone defects, because large amounts of bone can be regenerated in the distraction gap. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, angiogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Regenerate bone forms by three modes of ossification, which include intramembranous, enchondral, and transchondroid ossifications, although intramembraneous bone formation is the predominant mechanism of ossification. In this review we discussed the coupling between angiogenesis and mineralization, the biological and mechanical factors affecting them, the cellular and molecular events occurring during distraction osteogenesis, and the emerging modalities to accelerate regenerate bone healing and remodeling.

Relationships between tissue dilatation and differentiation in distraction osteogenesis

“…The osteogenic effect of static, equibiaxial tensile stretch applied to osteoblasts in vitro has been shown previously (Fong et al, 2003). These results are consistent with the spatial correspondence observed between the regions experiencing static tensile stretch and those in which membranous bone formation occurs (Choi et al, 2002;Tay et al, 1998;Yasui et al, 1997;Yeung et al, 2002). At present, however, it is not known if it is the static nature of the physical stimulus per se that promotes these osteogenic phenomena.…”

Damaging Fatigue Loading Stimulates Increases in Periosteal Vascularity at Sites of Bone Formation in the Rat Ulna

“…The spatial pattern of vascular increase is established by day 3, prior to the accrual of significant woven bone. It has been noted that the vasculature provides a spatial template for bone formation in the developing skeleton [1,2] and in distraction osteogenesis [7,8,10,33]. We did not determine if individual vessels served as the templates for local bone formation after fatigue loading, although each marrow-like space within the woven bone contained at least one blood vessel and the "endosteal" surface of these spaces were lined with osteoblasts.…”

“…Bone formation during distraction osteogenesis is predominantly intramembranous, with fibrous tissue being replaced directly by bone [8][9][10]33]. Histologically, bone formation in distraction osteogenesis proceeds as mesenchymal fibroblasts in the gap proliferate and deposit a collagen fiber matrix that is invaded by vascular channels; these vessels in turn appear to provide the appropriate local environment for osteoblastic differentiation and bone formation [7,10,34]. Our histological observations support a similar sequence of events in the formation of periosteal bone after fatigue loading, although without the deposition of a provisional fibrous matrix.…”

“…For example, angiogenesis plays an important role during skeletal development [2][3][4], fracture healing [5,6], distraction osteogenesis [7][8][9][10][11] and cortical defect healing [12].…”

Distraction Osteogenesis and Its Challenges in Bone Regeneration

“…DO is a vascular dependent process and new bone formation in DO is associated with robust neo-angiogenesis and neo-vascularity (Choi et al, 2000;Choi et al, 2002). There is an increased expression of numerous vascular growth factors in the distracted zone, including VEGF, HIF, basic FGF and Angiopoietin (Pacicca et al, 2003).…”