Fracture-healing is regulated in part by mechanical factors. Study of the processes by which the mechanical environment of a fracture modulates healing can yield new strategies for the treatment of bone injuries. This article focuses on several key unanswered questions in the study of mechanotransduction and fracture repair. These questions concern identifying the mechanical stimuli that promote bone-healing, defining the mechanisms that are involved in this process, and examining the potential for cross-talk between investigations of mechanotransduction in bone-healing and in healing of other mesenchymally derived tissues. Several approaches to obtain accurate estimates of the mechanical stimuli present within a fracture callus are proposed, and our current understanding of the mechanotransduction processes involved in bone-healing is reviewed. Further study of mechanotransduction mechanisms is needed in order to identify those that are most critical and active during the various phases of fracture repair. A better understanding of the effect of mechanical factors on bone-healing will also benefit the study of healing, regeneration, and engineering of other skeletal tissues.
The Mechanical Environment of a Healing FractureFracture-healing is governed by genetic as well as epigenetic factors. The mechanical environment of a healing fracture is one such epigenetic factor that is known to have a profound influence on the rate and success of the repair process. Understanding the effect of the mechanical environment, and in particular the mechanisms by which mechanical cues modulate bone-healing, has applications ranging from clinical management of fractures to bone-tissue engineering and basic science investigations of cell fate.Multiple parameters contribute to the mechanical environment of a fracture callus. These include the stability of fixation, the geometry or type of fracture, and the type of loading. For example, highly stable fixation, such as that provided by a rigidly applied internal fixation plate and by an interfragmentary screw, results in primary cortical healing without the formation of a callus. Less stable external fixation results in a cartilaginous callus, the size of which depends heavily on the stiffness of the fixator frame 1-3 . The geometry or type of fracture affects how the external loads are transferred to the callus tissue. A simple example is the comparison of a transverse fracture line to an oblique fracture line. Even under the same axial compressive Corresponding author: Elise F. Morgan, PhD, Department of Aerospace and Mechanical Engineering, Boston University, 110 Cummington Street, Boston, MA 02215. E-mail address: efmorgan@bu.edu. Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the National Institutes of Health (grant #AR053353) and the Whitaker Foundation (graduate fellowship) and of less than $10,000 from Boston University (undergraduate ...