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Simulation of the Cellular Dynamics of Bone Remodeling and its Control Mechanisms

Amiri, Behnam | 2015

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 47708 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Zohoor, Hassan; Sohrabpour, Saeed
  7. Abstract:
  8. Bone is one of the most important biomechanical organs in animal bodies which comprises of a dynamic tissue that can change its internal structure through remodeling process. A comprehensive understanding of this process is of great significance in prevention and cure of many bone diseases. Due to the special conditions of hard bone tissue, empirical studies on the details of bone processes is very costly and time consuming. Thus, mathematical models and in silico simulations are key to unraveling how bone homeostasis imbalance can lead to pathological conditions. Therefore, in the recent years, there has been an increasing interest in modeling bone remodeling process in cellular level. In the first part of this research, Cellular Potts Model is extended to introduce a novel cell-based computational model which can aptly describe the bone remodeling process in a single cortical BMU. The cell based model is then coupled with a finite element algorithm to evaluate strain energy density in bone tissue and also with a set of reaction-diffusion PDE equations to evaluate concentration distribution of biochemical factors. In the second part, the model is employed to investigate popular hypotheses for bone remodeling regulation mechanisms in the literature. Eight regulatory mechanisms are added to the model and the effect of each factor on the behavior of a cortical BMU is investigated through various simulations with different mechanical loads and microdamages. The computational model demonstrates how a variety of biochemical and mechanical control loops determine the dynamics of BMU. Regarding the achieved results, all the investigated regulatory factors have critical roles in the process of origination, maintenance and termination of BMU. The introduced model provides a way to formalize and understand the underlying mechanisms of bone remodeling which can lead to more effective treatment of bone diseases. Finally, due to the extendable structure of the model, it can be supplemented by including more biochemical regulatory pathways
  9. Keywords:
  10. Bone Remodeling ; Agent Based Model ; Bone Basic Multicellular Unit ; Biological Control Mechanisms

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