Insights into the Cellular and Molecular Mechanisms That Govern the Fracture-Healing Process: A Narrative Review

Abstract

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.

The bioelectrical properties of bone tissue

“…Bone defect healing is a complex physiological process involving hemorrhage, coagulation, inflammation, angiogenesis, cell migration, and progressive tissue remodeling, which has been described in detail in several excellent reviews. 66 , 67 , 68 The focus here will be on how the electrophysiological properties of bone tissue changes during injury, and how these in turn influence bone defect healing and regeneration. Injury of bone tissue is associated with reduced electrical potential at the defect site.…”

Latest Progress of LIPUS in Fracture Healing

“…The acute fracture causes the instant destruction of the continuity and integrity of the bone structure. 13 Though physiotherapy and immobilization are mostly acquired to prevent further injury, cumulative evidence supports LIPUS as an effective and noninvasive therapy. LIPUS acts on cells/tissues by generating periodic pressure oscillations that are defined by frequency and intensity.…”

The local and systemic effects of immune function on fracture healing

“…Each of these stages involves the interaction of mediators (signaling molecules) with different cell types and cell populations acting within the local tissue environment. 1 Interestingly, while the focus of research was for some time on the behavior and activity of progenitor cells, recently it became clear that the innate immune system participates in this process of fracture repair with the involvement of macrophages, monocytes, neutrophils, natural killer (NK) cells, and a variety of cytokines. In addition, the adaptive immune system also contributes to this process, particularly the T and B lymphocytes.…”