Simulating localised cellular inflammation and substrate properties in a strain energy density based bone remodelling algorithm for use in modelling trauma

Abstract

Bone responds to mechanical stimulus and a range of pre-existing finite element models have been suggested to reproduce the internal physiological structure of bone. Inflammation effects are not included in these models, yet inflammation is a key component of bone repair in trauma. Therefore, a model is proposed and tested here that extends these methods to include parameters that could be considered to represent the behaviour of bone remodelling when influenced by inflammation. The proposed model regulates remodelling based on findings from recent studies into the nature of heterotopic ossification, the formation of heterotopic bone, which have revealed information about the nature of bone after high levels of trauma. These parameters include consideration of the distance from the zone of trauma, the density of mesenchymal stem cells, and substrate stiffness as a trigger for cells becoming osteogenic. The method is tested on a two-dimensional plate model and shows that the new extended algorithm can produce a range of structures depending on inputs that could be used in the future to replicate physiological scenarios.

Challenges of heterotopic ossification—Molecular background and current treatment strategies

“…The first step of HO formation is local inflammation, evoked in response to various stimulae such as trauma, spinal cord injury, traumatic brain injury, surgical intervention, deep burns and others . The presence of inflammatory cells, including macrophages, lymphocytes, and mast cells, in the perivascular region of early HO lesions is associated with damage of skeletal muscle cells and tissue hypoxia, which can trigger the proliferation of undifferentiated progenitor cells.…”

Application of a mechanobiological algorithm to investigate mechanical mediation of heterotopic bone in trans-femoral amputees

“…The remodelling algorithm from Mullender et al . 41 was expanded to consider remodelling in soft tissue that was regulated with an extra factor, β , that increased with proximity to a specified wound site and with tissue strain 44 . This factor can be used to regulate the density change in each element including soft tissue.…”

“…A summary of all the parameters used on the models is shown in Table 3 . A more comprehensive study into these different parameters, including a sensitivity analysis, was conducted in previous work by the authors 40 , 44 . Only the parameters that were found to manipulate the shape of the HO are presented here.…”

Molecular and genetic mechanisms of heterotopic ossification

“…По мнению M. Reichel и соавт. [36], КМБ9 отводится ключевая роль в молекулярном патогенезе формирования очагов ГО, а его активность напрямую зависит от микроокружения скелетной мускулатуры. Важно отметить, что у пациентов с уже имеющимися признаками ГО после выполнения операции тотального эндопротезирования тазобедренных суставов, отмечено значительное повышение экспрессии изоформы TGF-β2.…”