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Developing Approaches for Computational Modelling of a Nanoprinted Structure in an In Vitro Osteocyte Model
Nanoprinting has enabled the creation of osteocyte scale structures to investigate the mechnobiological processes involved in cell to cell signalling. Applying computational simulation techniques to model the domain poses a challenge yet will allow insight into loading and cell to cell communication
Keywords: In Vitro, Osteocyte, Computational Modelling, Meshing, Finite Element Analysis, Computational Fluid Dynamics
Osteocytes are widely accepted to be the main mechanosensor in bone [1]. Embedded deep in the mineralized matrix of our bones, osteocytes form a vast cellular network. They orchestrate bone remodeling by sensing the loads bone is subjected to and for transducing these signal to effector cells. However, it remains unclear which mechanical signal is sensed by osteocytes. Fluid flow through the cavity and channel system that osteocytes reside in is hypothesized to be one important factor. Studying this requires an in vitro system mimicking the natural 3D environment of these cells. Using state-of-the-art micro-3D printing in combination with live cell microscopy, we have established a novel in vitro model that mimics the natural 3D environment of these cells. This involves printing structures containing cavities interconnected by channels at a level of micron scale accuracy and then seeding this structure with osteocytes. These cells then grow into the structure and ideally, will provide an accurate in vitro model mimicking in vivo cell function.
It has been suggested and demonstrated that both strain and fluid flow stresses can be used as a measure of mechano-stimulation in bone tissue [2, 3]. Hence, the proposed concept for our in vitro osteocyte model system would be the representation of mechanical stimulation in the bone environment by the induction of a variety of mechanical stimuli indirectly, either via fluid shear stresses or via structural strain, onto the osteocytes. Due to the nature of the system, a series of computational simulations will provide an excellent starting point for the investigation of the effect of application of structure wide mechanical forces.
[1] M.B. Schaffler, W.Y. Cheung, R. Majeska, O. Kennedy, Osteocytes: master orchestrators of bone, Calcified tissue international 94(1) (2014) 5-24.
[2] Y. Kameo, T. Adachi, Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation, Biomechanics and modeling in mechanobiology 13(4) (2014) 851-860.
[3] D.J. Webster, P.L. Morley, G.H. van Lenthe, R. Muller, A novel in vivo mouse model for mechanically stimulated bone adaptation - a combined experimental and computational validation study, Comput Method Biomec 11(5) (2008) 435-441.
Osteocytes are widely accepted to be the main mechanosensor in bone [1]. Embedded deep in the mineralized matrix of our bones, osteocytes form a vast cellular network. They orchestrate bone remodeling by sensing the loads bone is subjected to and for transducing these signal to effector cells. However, it remains unclear which mechanical signal is sensed by osteocytes. Fluid flow through the cavity and channel system that osteocytes reside in is hypothesized to be one important factor. Studying this requires an in vitro system mimicking the natural 3D environment of these cells. Using state-of-the-art micro-3D printing in combination with live cell microscopy, we have established a novel in vitro model that mimics the natural 3D environment of these cells. This involves printing structures containing cavities interconnected by channels at a level of micron scale accuracy and then seeding this structure with osteocytes. These cells then grow into the structure and ideally, will provide an accurate in vitro model mimicking in vivo cell function.
It has been suggested and demonstrated that both strain and fluid flow stresses can be used as a measure of mechano-stimulation in bone tissue [2, 3]. Hence, the proposed concept for our in vitro osteocyte model system would be the representation of mechanical stimulation in the bone environment by the induction of a variety of mechanical stimuli indirectly, either via fluid shear stresses or via structural strain, onto the osteocytes. Due to the nature of the system, a series of computational simulations will provide an excellent starting point for the investigation of the effect of application of structure wide mechanical forces.
[1] M.B. Schaffler, W.Y. Cheung, R. Majeska, O. Kennedy, Osteocytes: master orchestrators of bone, Calcified tissue international 94(1) (2014) 5-24. [2] Y. Kameo, T. Adachi, Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation, Biomechanics and modeling in mechanobiology 13(4) (2014) 851-860. [3] D.J. Webster, P.L. Morley, G.H. van Lenthe, R. Muller, A novel in vivo mouse model for mechanically stimulated bone adaptation - a combined experimental and computational validation study, Comput Method Biomec 11(5) (2008) 435-441.
The greater aim of this project is the investigation, via computational models, of various loading modalities of this aforementioned 3D printed structure and the cells within. However, the first step is the conversion of the physical structure to an appropriate computational representation. Hence the aim of this project is the development of an approach to represent the structure in an appropriate computational domain, such as discretization into a mesh as is done in finite element analysis or other appropriate domain description.
The greater aim of this project is the investigation, via computational models, of various loading modalities of this aforementioned 3D printed structure and the cells within. However, the first step is the conversion of the physical structure to an appropriate computational representation. Hence the aim of this project is the development of an approach to represent the structure in an appropriate computational domain, such as discretization into a mesh as is done in finite element analysis or other appropriate domain description.