Abstract
BackgroundBone 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 bone healing. However, the effects of initial healing phase, which includes the inflammatory stage, the granulation tissue formation, and the initial callus formation during the first few days post-fracture, are generally neglected in such studies.MethodsIn 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.ResultsThe results quantified how faster MSC migration, stiffer granulation tissue, thicker callus, and smaller interfragmentary gap enhanced healing to some extent. However, 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.ConclusionsFindings from this paper quantified the effects of the initial healing phase on healing outcome to better understand the biological and mechanobiological mechanisms and their utilization in the design and optimization of treatment strategies. It is also demonstrated through a simulation 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.
Highlights
Bone healing process includes four phases: inflammatory response, soft callus formation, hard callus development, and remodeling
Most mechanobiological models of bone healing consider a predefined callus with an ideal fixed geometry and predefined material properties [12,13,14, 21], where they neglect the initial phases of healing [1]
We considered the time associated with complete development of the following structures as possible healing indices: 1) cartilaginous callus (CC), 2) bony bridging (BB), and 3) bony callus (BC) [31, 44]
Summary
Bone healing process includes four phases: inflammatory response, soft callus formation, hard callus development, and remodeling. Bone healing is a complex four-phase process, which starts with an inflammatory response and hematoma formation, resulting in granulation tissue development at 3– 7 days post-fracture Following this initial phase, a Ghiasi et al BMC Musculoskeletal Disorders (2019) 20:562 outcomes under different mechanical or biological conditions; and in response to new treatment strategies [9,10,11]. These numerical mechanisms (i.e. thermal expansion and swelling pressure) are regulated through mechanobiological rules and should be considered as an improvement in accounting for callus geometry development; they may not simulate the actual mechanism of callus geometry development, especially during the initial phase of healing [1] Another limitation of the current studies is characterization of the material properties of the hematoma and granulation tissue during the initial phase [1, 21, 26, 27]
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