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Bone healing process includes four phases: inflammatory response, soft callusformation, hard callus development, and remodeling. Mechanobiological modelshave been used to investigate the role of various mechanical and biologicalfactors on the bone healing. However, the initial phase of healing, whichincludes the inflammatory response, the granulation tissue formation and theinitial callus formation during the first few days post-fracture, are generallyneglected in such studies. In this study, we developed a finite-element-basedmodel to simulate different levels of diffusion coefficient for mesenchymalstem cell (MSC) migration, Young's modulus of granulation tissue, callusthickness and interfragmentary gap size to understand the modulatory effects ofthese initial phase parameters on bone healing. The results showed that fasterMSC migration, stiffer granulation tissue, thicker callus and smallerinterfragmentary gap enhanced healing to some extent. After a certainthreshold, a state of saturation was reached for MSC migration rate,granulation tissue stiffness and callus thickness. Therefore, a parametricstudy was performed to verify that the callus formed at the initial phase, inagreement with experimental observations, has an ideal range of geometry andmaterial properties to have the most efficient healing time. Findings from thispaper quantified the effects of the healing initial phase on healing outcome tobetter understand the biological and mechanobiological mechanisms and theirutilization in the design and optimization of treatment strategies. Simulationoutcomes also demonstrated that for fractures, where bone segments are in closeproximity, callus development is not required. This finding is consistent withthe concepts of primary and secondary bone healing.

Computational Modeling of the Effects of Inflammatory Response and Granulation Tissue Properties on Human Bone Fracture Healing