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After fracture, mesenchymal stem cells (MSCs) and growth factors migrate into the fracture callus to exert their biological actions. Previous studies have indicated that dynamic loading induced tissue deformation and interstitial fluid flow could produce a biomechanical environment which significantly affects the healing outcomes. However, the fundamental relationship between the various loading regimes and different healing outcomes has not still been fully understood. In this study, we present an integrated computational model to investigate the effect of dynamic loading on early stage of bone fracture healing. The model takes into account cell and growth factor transport under dynamic loading, and mechanical stimuli mediated MSC differentiation and tissue production. The developed model was firstly validated by the available experimental data, and then implemented to identify the loading regimes that produce the optimal healing outcomes. Our results demonstrated that dynamic loading enhances MSC and growth factor transport in a spatially dependent manner. For example, compared to free diffusion, dynamic loading could significantly increase MSCs concentration in endosteal zone; and chondrogenic growth factors in both cortical and periosteal zones in callus. Furthermore, there could be an optimal dynamic loading regime (e.g. 10% strain at 1 Hz) which could potentially significant enhance endochondral ossification.

A great deal of evidence suggests that partial weight-bearing exercise plays an important role in bone fracture healing. However, current physiotherapy program tends to follow the "Let's try it and see" strategy due to the lack of a fundamental understanding of in vivo mechanical environment required for the better healing outcomes. The purpose of present study is to develop an innovative framework to predict the healing outcomes as a result of post-surgical physical therapy. The raw acceleration data corresponding to a series of walking tests is firstly captured by ActiGraph accelerometers, and then used as input to theoretically estimate the peak ground reaction force (PGRF) and peak loading rate (PLR). Finally, the healing outcomes as a result of different walking speeds are predicated based on the interfragmentary movement (IFM) measured by using mechanical testing. The results show that PGRF and PLR are important factors for the callus tissue differentiation at the early stage of healing. The developed model could potentially allow the design of effective patient specific post-surgical physical therapy., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

Spatially resolved wavefront measurements are presented during nonlinear self-collapse and provide the first detailed characterization of wavefront evolution during filament formation. The wavefront dynamics of key nonlinear processes including Kerr self-focusing, ionization and plasma defocusing, and dynamic spatial replenishment are identified and resolved in both the filament core and reservoir regions. These results are analyzed and interpreted with respect to numerical simulations and provide insight into fundamental aspects of filamentation. They also inform applications based on phase manipulation, such as external beam guiding, and present a new method for measuring the nonlinear index of refraction, n2. [ABSTRACT FROM AUTHOR]

Flexible fixation or the so-called 'biological fixation' has been shown to encourage the formation of fracture callus, leading to better healing outcomes. However, the nature of the relationship between the degree of mechanical stability provided by a flexible fixation and the optimal healing outcomes has not been fully understood. In this study, we have developed a validated quantitative model to predict how cells in fracture callus might respond to change in their mechanical microenvironment due to different configurations of locking compression plate (LCP) in clinical practice, particularly in the early stage of healing. The model predicts that increasing flexibility of the LCP by changing the bone-plate distance (BPD) or the plate working length (WL) could enhance interfragmentary strain in the presence of a relatively large gap size (>3 mm). Furthermore, conventional LCP normally results in asymmetric tissue development during early stage of callus formation, and the increase of BPD or WL is insufficient to alleviate this problem. [ABSTRACT FROM AUTHOR]

1. Bone is a remarkable living tissue that provides a framework for animal body support and motion. However, under excessive loads and deformations, bone is prone is to damage through fracture. Furthermore, once the bone is weakened by osteoporosis, bone fracture can occur even after only minimal trauma. 2. Various techniques have been developed to treat bone fractures. Successful treatment outcomes depend on a fundamental understanding of the biochemical and biomechanical environments of the fracture site. Various cell types (e.g. mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts) within the fracture site tightly control the healing process by responding to the chemical and mechanical microenvironment. However, these mechanochemical regulatory mechanisms remain poorly understood at the system level owing to the large range of variables, such as age, sex and disease-associated material properties of the tissue. 3. Computational modelling can play an important role in unravelling this complexity by combining mechanochemical interactions, revealing the dominant controlling processes and optimizing system behaviour, thereby enabling the development and evaluation of treatment strategies for individual patients. [ABSTRACT FROM AUTHOR]

Mechano-regulation plays a crucial role in bone healing and involves complex cellular events. In this study, we investigate the change of mechanical microenvironment of stem cells within early fracture callus as a result of the change of fracture obliquity, gap size and fixation configuration using mechanical testing in conjunction with computational modelling. The research outcomes show that angle of obliquity ( θ ) has significant effects on interfragmentary movement (IFM) which influences mechanical microenvironment of the callus cells. Axial IFM at near cortex of fracture decreases with θ , while shear IFM significantly increases with θ . While a large θ can increase shear IFM by four-fold compared to transverse fracture, it also result in the tension–stress effect at near cortex of fracture callus. In addition, mechanical stimuli for cell differentiation within the callus are found to be strongly negatively correlated to angle of obliquity and gap size. It is also shown that a relatively flexible fixation could enhance callus formation in presence of a large gap but could lead to excessive callus strain and interstitial fluid flow when a small transverse fracture gap is present. In conclusion, there appears to be an optimal fixation configuration for a given angle of obliquity and gap size. [ABSTRACT FROM AUTHOR]