Clinical School (Royal Melbourne Hospital) - Research Publications
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ItemThe role of impairment of mesenchymal stem cell function in osteoporotic bone fracture healingZhang, L ; Miramini, S ; Richardson, M ; Mendis, P ; Ebeling, P (SPRINGER, 2017-09-01)With demographic change and increasing life expectancy, osteoporotic fractures have become one of the most prevalent trauma conditions seen in daily clinical practice. A variety of factors are known to affect the rate of healing in osteoporotic conditions (e.g. both biochemical and biomechanical environment of callus cells). However, the influence of impairment of mesenchymal stem cell function in the osteoporotic condition on bone fracture healing has not been fully understood. In the present study, we develop a mathematical model that quantifies the change in biological processes within the fracture callus as a result of osteoporosis. The model includes special features of osteoporosis such as reduction in mesenchymal stem cell (MSC) number in osteoporotic bone, impaired response of osteoporotic MSCs to their biomechanical microenvironment and the effects of configuration of locking compression plate (LCP) system on healing in this context. The results presented here suggest that mechanically-mediated MSCs differentiation at early stages of healing are significantly affected under osteoporotic conditions, while it is predicted that the flexible fixation achieved by increasing bone-plate distance of LCP could alleviate the negative effects of osteoporosis on healing. The outcomes of this study could potentially lead to patient specific surgical solutions, and thus achieve optimal healing outcomes in osteoporotic conditions.
ItemThe relationship between interfragmentary movement and cell differentiation in early fracture healing under locking plate fixationMiramini, S ; Zhang, L ; Richardson, M ; Mendis, P ; Oloyede, A ; Ebeling, P (Springer Netherlands, 2016)Interfragmentary movement (IFM) at the fracture site plays an important role in fracture healing, particularly during its early stage, via influencing the mechanical microenvironment of mesenchymal stem cells within the fracture callus. However, the effect of changes in IFM resulting from the changes in the configuration of locking plate fixation on cell differentiation has not yet been fully understood. In this study, mechanical experiments on surrogate tibia specimens, manufactured from specially formulated polyurethane, were conducted to investigate changes in IFM of fractures under various locking plate fixation configurations and loading magnitudes. The effect of the observed IFM on callus cell differentiation was then further studied using computational simulation. We found that during the early stage, cell differentiation in the fracture callus is highly influenced by fracture gap size and IFM, which in turn, is highly sensitive to locking plate fixation configuration. The computational model predicted that a small gap size (e.g. 1 mm) under a relatively flexible configuration of locking plate fixation (larger bone-plate distances and working lengths) could experience excessive strain and fluid flow within the fracture site, resulting in excessive fibrous tissue differentiation and delayed healing. By contrast, a relatively flexible configuration of locking plate fixation was predicted to improve cartilaginous callus formation and bone healing for a relatively larger gap size (e.g. 3 mm). If further confirmed by animal and human studies, the research outcome of this paper may have implications for orthopaedic surgeons in optimising the application of locking plate fixations for fractures in clinical practice.