  Bone healing process includes four phases: inflammatory response, soft callus
formation, hard callus development, and remodeling. Mechanobiological models
have been used to investigate the role of various mechanical and biological
factors on the bone healing. However, the initial phase of healing, which
includes the inflammatory response, the granulation tissue formation and the
initial callus formation during the first few days post-fracture, are generally
neglected in such studies. In this study, we developed a finite-element-based
model to simulate different levels of diffusion coefficient for mesenchymal
stem cell (MSC) migration, Young's modulus of granulation tissue, callus
thickness and interfragmentary gap size to understand the modulatory effects of
these initial phase parameters on bone healing. The results showed that faster
MSC migration, stiffer granulation tissue, thicker callus and smaller
interfragmentary gap enhanced healing to some extent. After a certain
threshold, a state of saturation was reached for MSC migration rate,
granulation tissue stiffness and callus thickness. Therefore, a parametric
study was performed to verify that the callus formed at the initial phase, in
agreement with experimental observations, has an ideal range of geometry and
material properties to have the most efficient healing time. Findings from this
paper quantified the effects of the healing initial phase on healing outcome to
better understand the biological and mechanobiological mechanisms and their
utilization in the design and optimization of treatment strategies. Simulation
outcomes also demonstrated that for fractures, where bone segments are in close
proximity, callus development is not required. This finding is consistent with
the concepts of primary and secondary bone healing.
