Computational modeling of human bone fracture healing affected by different conditions of initial healing stage.

BACKGROUND: 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 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. METHODS: 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. RESULTS: The 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. CONCLUSIONS: Findings 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.

Cross-sectional area of human trunk paraspinal muscles before and after posterior lumbar surgery using magnetic resonance imaging.

PURPOSE: Iatrogenic injuries to paraspinal muscles during the posterior lumbar surgery (PLS) cause a reduction in their cross-sectional areas (CSAs) and contractile densities over time post-surgery. This study aims to quantify such alterations. METHOD: Pre- and postoperative CSAs (~6 months interval) of all paraspinal muscles were measured in six patients undergoing PLS using a 3-T magnetic resonance (MR) scanner to quantify the alterations in geometrical and tissue effective contractile (non-fatty) CSAs of these muscles at all lumbar levels. To examine the presence of any confounding effects on recorded changes within ~7-month period, measurements were also carried out on ten healthy volunteers. RESULTS: In the healthy population, an important (~22%) portion of CSA of the erector spinae (ES) was noncontractile at the lower lumbar levels. Negligible variations over time in both the total geometrical (<1.7% in average) and contractile (<1.2%) CSAs of muscles were observed in the healthy group (i.e., no confounding effect). Following PLS, significant reductions were observed in the geometrical CSA of only multifidus (MF) muscle by ~14 and 11% as well as in its contractile CSA by ~26 and 14% at the L5-S1 and L4-L5 levels, respectively. CONCLUSION: The total CSA of ES at lower lumbar levels shows substantial noncontractile contents in both healthy and patient populations. Biomechanical models of the spine should hence account for the noncontractile contents using only the effective contractile muscle CSAs. Postoperative variations in CSAs of paraspinal muscles may have profound effects on patterns of muscle activities, spinal loading, and stability.

Bone fracture healing in mechanobiological modeling: A review of principles and methods.

Bone fracture is a very common body injury. The healing process is physiologically complex, involving both biological and mechanical aspects. Following a fracture, cell migration, cell/tissue differentiation, tissue synthesis, and cytokine and growth factor release occur, regulated by the mechanical environment. Over the past decade, bone healing simulation and modeling has been employed to understand its details and mechanisms, to investigate specific clinical questions, and to design healing strategies. The goal of this effort is to review the history and the most recent work in bone healing simulations with an emphasis on both biological and mechanical properties. Therefore, we provide a brief review of the biology of bone fracture repair, followed by an outline of the key growth factors and mechanical factors influencing it. We then compare different methodologies of bone healing simulation, including conceptual modeling (qualitative modeling of bone healing to understand the general mechanisms), biological modeling (considering only the biological factors and processes), and mechanobiological modeling (considering both biological aspects and mechanical environment). Finally we evaluate different components and clinical applications of bone healing simulation such as mechanical stimuli, phases of bone healing, and angiogenesis.