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Register a new userTowards a New Spatial Representation of Bone Remodeling
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Irregular bone remodeling is associated with a number of bone diseases such as osteoporosis and multiple myeloma. Computational and mathematical modeling can aid in therapy and treatment as well as understanding fundamental biology. Different approaches to modeling give insight into different aspects of a phenomena so it is useful to have an arsenal of various computational and mathematical models. Here we develop a mathematical representation of bone remodeling that can effectively describe many aspects of the complicated geometries and spatial behavior observed. There is a sharp interface between bone and marrow regions. Also the surface of bone moves in and out, i.e. in the normal direction, due to remodeling. Based on these observations we employ the use of a level-set function to represent the spatial behavior of remodeling. We elaborate on a temporal model for osteoclast and osteoblast population dynamics to determine the change in bone mass which influences how the interface between bone and marrow changes. We exhibit simulations based on our computational model that show the motion of the interface between bone and marrow as a consequence of bone remodeling. The simulations show that it is possible to capture spatial behavior of bone remodeling in complicated geometries as they occur emph{in vitro} and emph{in vivo}. By employing the level set approach it is possible to develop computational and mathematical representations of the spatial behavior of bone remodeling. By including in this formalism further details, such as more complex cytokine interactions and accurate parameter values, it is possible to obtain simulations of phenomena related to bone remodeling with spatial behavior much as emph{in vitro} and emph{in vivo}. This makes it possible to perform emph{in silica} experiments more closely resembling experimental observations.
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Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. This is particularly true with respect to the mathematical modeling of bone remodeling. However, there is increasing evidence that osteocytes play important roles in the cycle of targeted bone remodeling, in serving as a significant source of RANKL to support osteoclastogenesis, and in secreting the bone formation inhibitor sclerostin. Moreover, there is also increasing interest in sclerostin, an osteocyte-secreted bone formation inhibitor, and its role in regulating local response to changes in the bone microenvironment. Here we develop a cell population model of bone remodeling that includes the role of osteocytes, sclerostin, and allows for the possibility of RANKL expression by osteocyte cell populations. This model extends and complements many of the existing mathematical models for bone remodeling but can be used to explore aspects of the process of bone remodeling that were previously beyond the scope of prior modeling work. Through numerical simulations we demonstrate that our model can be used to theoretically explore many of the most recent experimental results for bone remodeling, and can be utilized to assess the effects of novel bone-targeting agents on the bone remodeling process.
Bone remodeling involves the coordinated removal of bone by osteoclasts and addition of bone by osteoblasts, a process that is modulated by the prevailing mechanical environment. In this paper a fully coupled model of bone remodeling is developed, based on coupling a bone cell population model with a micromechanical homogenization scheme of bone stiffness. While the former model considers biochemical regulatory mechanisms between bone cells such as the RANK-RANKL-OPG pathway and action of TGF-beta, the latter model allows for accurate upscaling of the mechanical properties of bone. Importantly, we consider bone remodeling as being controlled proportionally to the microscopic strain energy density, on the observation scale where the sensing of the mechanical loading takes place, estimated by means of continuum micromechanics-based strain concentration. This approach allows to address two fundamental questions of bone biology: (i) How do biochemical changes influence bone remodeling and so affect the composition and mechanical properties of bone? and (ii) What mechanisms are responsible for mechanoregulation of bone remodeling? Numerical studies highlight the conceptual advantage of this new approach compared to conventional phenomenological models. It is demonstrated that the proposed model is able to simulate changes of the bone constituent volume fractions that are in qualitative agreement with experimental observations for osteoporotic and disuse syndromes.
Bone regeneration is a clinical challenge that requires multiple approaches. Sometimes, it also includes the development of new osteogenic and antibacterial biomaterials to treat the occurrence of possible infection processes derived from surgery. This study evaluates the antibacterial properties of meso-macroporous scaffolds coated with gelatin and based on a bioactive glass and after being doped with 4% ZnO (4ZN-GE) and loaded with saturated and minimally inhibitory concentrations of one of the antibiotics levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After the physicochemical characterization of the materials, inorganic ion and antibiotic release studies were performed from the scaffolds. In addition, molecular modeling allowed the determination of electrostatic potential density maps and hydrogen bonds of the antibiotics and the glass matrix. In vitro antibacterial studies (in plankton, inhibition halos and biofilm destruction) with S. aureus and E. coli as model bacteria showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in cultures of E. coli with LEVO or GENTA. Furthermore, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and total destruction of E. coli biofilm was achieved with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide much needed options for the treatment of bone infection.
In this paper, we describe a Graphical User Interface (GUI) designed to manage large quantities of image data of a biological system. After setting the design requirements for the system, we developed an ecology quantification GUI that assists biologists in analysing data. We focus on the main features of the interface and we present the results and an evaluation of the system. Finally, we provide some directions for some future work.
Bone is a biomaterial undergoing continuous renewal. The renewal process is known as bone remodelling and is operated by bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Both biochemical and biomechanical regulatory mechanisms have been identified in the interaction between osteoclasts and osteoblasts. Here we focus on an additional and poorly understood potential regulatory mechanism of bone cells, that involves the morphology of the microstructure of bone. Bone cells can only remove and replace bone at a bone surface. However, the microscopic availability of bone surface depends in turn on the ever-changing bone microstructure. The importance of this geometrical dependence is unknown and difficult to quantify experimentally. Therefore, we develop a sophisticated mathematical model of bone cell interactions that takes into account biochemical, biomechanical and geometrical regulations. We then investigate numerically the influence of bone surface availability in bone remodelling within a representative bone tissue sample. The interdependence between the bone cells activity, which modifies the bone microstructure, and changes in the microscopic bone surface availability, which in turn influences bone cell development and activity, is implemented using a remarkable experimental relationship between bone specific surface and bone porosity. Our model suggests that geometrical regulation of the activation of new remodelling events could have a significant effect on bone porosity and bone stiffness. On the other hand, geometrical regulation of late stages of osteoblast and osteoclast differentiation seems less significant. We conclude that the development of osteoporosis is probably accelerated by this geometrical regulation in cortical bone, but probably slowed down in trabecular bone.
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