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Bone healing is a complex biological procedure in which several cellular actions, directed by biochemical and mechanical signals, take place. Experimental studies have shown that ultrasound accelerates bone ossification and has a multiple influence on angiogenesis. In this study a mathematical model predicting bone healing under the presence of ultrasound is demonstrated. The primary objective is to account for the ultrasound effect on angiogenesis and more specifically on the transport of the Vascular Endothelial Growth Factor (VEGF). Partial differential equations describing the spatiotemporal evolution of cells, growth factors, tissues and ultrasound acoustic pressure and velocity equations determining the development of the blood vessel network constitute the present model. The effect of the ultrasound characteristics on angiogenesis and bone healing is investigated by applying different boundary conditions of acoustic pressure at the periosteal region of the bone model, which correspond to different intensity values. The results made clear that ultrasound enhances angiogenesis mechanisms during bone healing. The proposed model could be regarded as a step towards the monitoring of the effect of ultrasound on bone regeneration.

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Computational studies on the evaluation of bone status in cases of pathologies have gained significant interest in recent years. This work presents a parametric and systematic numerical study on ultrasound propagation in cortical bone models to investigate the effect of changes in cortical porosity and the occurrence of large basic multicellular units, simply called non-refilled resorption lacunae (RL), on the velocity of the first arriving signal (FAS). Two-dimensional geometries of cortical bone are established for various microstructural models mimicking normal and pathological tissue states. Emphasis is given on the detection of RL formation which may provoke the thinning of the cortical cortex and the increase of porosity at a later stage of the disease. The central excitation frequencies 0.5 and 1 MHz are examined. The proposed configuration consists of one point source and multiple successive receivers in order to calculate the FAS velocity in small propagation paths (local velocity) and derive a variation profile along the cortical surface. It was shown that: (a) the local FAS velocity can capture porosity changes including the occurrence of RL with different number, size and depth of formation; and (b) the excitation frequency 0.5 MHz is more sensitive for the assessment of cortical microstructure.

Quantitative ultrasound is a promising and relative recent method for the assessment of bone. In this work, the interaction of ultrasound with the porosity of cortical bone is investigated for different frequencies. Emphasis is given on the study of complex scattering effects induced by the propagation of an ultrasonic wave in osseous tissues. Numerical models of cortical bone are established with a porosity of 0, 5 and 10% corresponding to healthy homogeneous bone, healthy inhomogeneous bone and normal ageing, respectively. Different excitation frequencies are applied in the range 0.2-1 MHz. The scattering amplitude and the acoustic pressure are calculated for multiple angles and receiving positions focusing on the backward direction. The results indicate that the application of higher frequencies can better distinguish changes in the energy distribution in the backward direction due to alterations of the cortical porosity.

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Bone healing involves a series of complicated cellular and molecular mechanisms that result in bone formation. Several mechanobiological models have been developed to simulate these cellular mechanisms via diffusive processes. In most cases solution to diffusion equations is accomplished using the Finite Element Method (FEM) which however requires global remeshing in problems with moving or new born surfaces or material phases. This limitation is addressed in meshless methods in which no background cells are needed for the numerical solution of the integrals. In this study a new meshless Local Boundary Integral Equation (LBIE) method is employed for deriving predictions of cell proliferation during bone healing. First a benchmark problem is presented to assess the accuracy of the method. Then the LBIE method is utilized for the solution of cell diffusion problem in a two-dimensional (2D) model of fractured model. Our findings indicate that the proposed here LBIE method can successfully predict cell distributions during fracture healing.