Bridging technique and science: A review of the molecular signals from long bone development that guiding bone regeneration

Bone development is a sequence of coordinated events that eventually forms the skeleton. The regenerative capacity of bone is preserved through adulthood. After injury, bone can be restored to its functional and homeostatic state. Orthopaedic surgeons take advantage of this regenerative potential in procedures such as distraction osteogenesis where a low-energy fracture is created followed by distraction at a controlled rate to form new bone. This review uses the fundamental elements of distraction osteogenesis to understand the molecular pathways underlying skeletal development harnessed during injury and orthopaedic surgery to regenerate bone. We highlight the developmental origins of the axial skeleton with an emphasis on the molecular signals driving the bone development. Additionally, we discuss the role of major signaling pathways during bone regeneration and highlight how bone regeneration recapitulates skeletal development. Although other pathways exist for this phenomenon such as anoxia, these pathways function during distraction osteogenesis has not been delineated from a basic science perspective. Finally, we review the four components of distraction osteogenesis that facilitate bone regeneration specifically outlining the best practices for tibial distraction.