Chapter 17 - The Role of the Immune System in Fracture Healing

Abstract

While developmental processes usually terminate when animals reach maturity, morphogenetic processes may be reinitiated in specific tissues as a consequence of injury. Fracture healing and bone repair are among the unique processes of postnatal tissue regeneration that are believed to mirror the ontological events that take place during embryological development of the skeleton. Many of the developmental processes and genes that are expressed preferentially in embryonic stem cells during the initiation and activation of the morphogenetic pathways of skeletal development are also expressed in fracture callus tissues. It is generally believed that it is the recapitulation of these ontological processes during fracture healing that allows bone to be repaired without the development of scar tissue, and ultimately leads to the regeneration of damaged tissue to its preinjury structure. This is in contrast to the repair of soft tissue that heals typically with some degree of fibroblastic scar formation. The interplay of a number of different tissues (vascular, hematopoietic, skeletal, and neural) is essential for the unimpeded regeneration of bone. Appropriate passage through this regenerative cascade is dependent on the proper orchestration of paracrine, autocrine, and systemic signaling pathways with the appropriate complement of stem cells needed to regenerate a skeletal organ. In context of the bone repair process both innate and adaptive immune cells and regulatory factors contribute to the initiation of the repair process, recruitment of skeletal stem cells, control of skeletal cell differentiation, and the remodeling of the regenerated tissues to the injured skeletal element’s original form and function.