Mechanobiology of Fracture Healing: Basic Principles and Applications in Orthodontics and Orthopaedics

Abstract

The Chapter describes how mechanobiological models can be utilized to predict the spatial and temporal patterns of the tissues differentiating within a fracture site during the healing process. It will be structured in four main Sections. Firstly, the basic principles of mechanobiology, the main theories and the principal models utilized to simulate the cellular processes involved in fracture healing will be illustrated. Second, two examples will be given showing how a mechano-regulation model, where the bone callus is modeled as a biphasic poroelastic material and the stimulus regulating tissue differentiation is hypothesized to be a function of the strain and fluid flow-, can be utilized to assess bone regeneration in an ostetomized mandible submitted to distraction osteogenesis and in a fractured lumbar vertebra. Finally, the main limitations of the model utilized and, in general, of mechanobiological algorithms as well as the future perspectives will be outlined. Fracture healing is a physiological process that initiates immediately after the fracture event and occurs by following two different modalities: by primary fracture healing or by secondary fracture healing. Primary healing involves a direct attempt by the cortex to reestablish itself once it has become interrupted. When stabilisation is not adequate to permit primary healing, the abundant capillaries required for bone repair are constantly ruptured and secondary healing takes place. Secondary healing involves responses within the periosteum and external soft tissues and subsequent formation of an external callus. Secondary fracture healing occurs in the following stages. Blood emanates from the ruptured vessels and a haemorrhage quickly fills the fracture gap space. Macrophages remove the dead tissue and generate initial granulation tissue for the migration of undifferentiated mesenchymal stem cells (MSCs), originating an initial stabilizing callus. These cells proliferate and migrate from the surrounding soft tissue (Einhorn, 1998, McKibbin, 1978) (Fig. 1a). Then, stem cells disperse into the fracture callus, divide (mitosis) and simultaneously migrate within the fracture site (Fig. 1b). In the next stage, mesenchymal cells may differentiate into chondrocytes, osteoblasts or fibroblasts, depending on the biological and mechanical conditions (Fig. 1c). These differentiated cells begin to synthesize the extracellular matrix of their corresponding tissue (Doblare et al., 2004) (Fig. 1d). Intramembranous woven bone is produced by direct differentiation of the stem cells into osteoblasts. Endochondral ossification occurs when chondrocytes are replaced by osteoblasts.