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Simulation and experimental characterisation of acoustic cell alignment device
We have developed an acoustofluidic device for alignment of cells inside a hydrogel fibre. Controlling the cell alignment spacing throughout the fibre is an important aspect of this project. This can be achieved by proper characterisation of the device by studying the acoustic modes.
Keywords: Acoustofluidics, Hydrogels, Tissue engineering, 3D cell culture
Spatial organisation of cells within a 3D biomaterial is an important challenge in tissue engineering. In this project we are developing an acoustofluidic device for tunable alignment of cells inside a solid hydrogel fibre.
A significant part of our knowledge about tissue structure and cell function can be attributed to years of research on understanding the fundamental biological processes through studies on cell biology and disease progression, using in vitro cell models grown on 2D flat surfaces of cell culture dishes and flasks. However, studies from Bissell and colleagues showed that normal human breast epithelial cells show tumour-like growth in conventional cell culture, but revert to normal when moved to a 3D scaffold mimicking the native cell environment [1]. Studies like these and others have made a case for the use of 3D cell culture techniques for developing cell/tissue models resembling native tissues. Hydrogels, due to their high water content, mechanical tunability, and microporous structure have been widely used as soft-tissue mimicking scaffolds for cell culture [2].
Some tissues, aside from being in a 3D matrix environment, display unique, tissue-specific cellular arrangement. For example, tissues such as muscles, tendons, and ligaments display parallel alignment of cells, which influences their anisotropic behaviour [3]. Research efforts have sought to mimic this cellular arrangement [4-6]. In our work, we use acoustophoresis to align cells directly within a hydrogel. Acoustophoresis uses sound waves to move cells, this allows for gentle, non-contact, label-free handling of cells [7]. Combining this technique with the properties of the hydrogel, we maintain the cellular positions and continuously produce a hydrogel fibre with aligned cells. These fibres can be used as functional micro- and macroscale tissues for regenerative medicine, ex vivo disease modeling, as well as the production of soft, living machines.
References:
[1] Petersen, O. W., Ronnov-Jessen, L., Howlett, A. R. & Bissell, M. J. Proceedings of the National Academy of Sciences 89, 9064–9068 (1992).
[2] Tibbitt, M. W. & Anseth, K. S., Biotechnology and Bioengineering (2009).
[3] Lanza R., Langer R., Vacanti J.P., Principles of Tissue Engineering: Fourth Edition, Elsevier (2013).
[4] Cui X, Gao G, Qiu Y. Accelerated myotube formation using bioprinting technology for biosensor applications. Biotechnol Lett. (2013).
[5] Ngan F. Huang, Shyam Patel, Rahul G. Thakar et al. Myotube Assembly on Nanofibrous and Micropatterned Polymers. (2006).
[6] An J, Teoh JEM, Suntornnond R, Chua CK. Design and 3D Printing of Scaffolds and Tissues. Engineering. (2015).
[7] Wiklund M. Acoustofluidics 12: Biocompatibility and cell viability in microfluidic acoustic resonators. Lab Chip. (2012).
Spatial organisation of cells within a 3D biomaterial is an important challenge in tissue engineering. In this project we are developing an acoustofluidic device for tunable alignment of cells inside a solid hydrogel fibre.
A significant part of our knowledge about tissue structure and cell function can be attributed to years of research on understanding the fundamental biological processes through studies on cell biology and disease progression, using in vitro cell models grown on 2D flat surfaces of cell culture dishes and flasks. However, studies from Bissell and colleagues showed that normal human breast epithelial cells show tumour-like growth in conventional cell culture, but revert to normal when moved to a 3D scaffold mimicking the native cell environment [1]. Studies like these and others have made a case for the use of 3D cell culture techniques for developing cell/tissue models resembling native tissues. Hydrogels, due to their high water content, mechanical tunability, and microporous structure have been widely used as soft-tissue mimicking scaffolds for cell culture [2].
Some tissues, aside from being in a 3D matrix environment, display unique, tissue-specific cellular arrangement. For example, tissues such as muscles, tendons, and ligaments display parallel alignment of cells, which influences their anisotropic behaviour [3]. Research efforts have sought to mimic this cellular arrangement [4-6]. In our work, we use acoustophoresis to align cells directly within a hydrogel. Acoustophoresis uses sound waves to move cells, this allows for gentle, non-contact, label-free handling of cells [7]. Combining this technique with the properties of the hydrogel, we maintain the cellular positions and continuously produce a hydrogel fibre with aligned cells. These fibres can be used as functional micro- and macroscale tissues for regenerative medicine, ex vivo disease modeling, as well as the production of soft, living machines. References:
[1] Petersen, O. W., Ronnov-Jessen, L., Howlett, A. R. & Bissell, M. J. Proceedings of the National Academy of Sciences 89, 9064–9068 (1992).
[2] Tibbitt, M. W. & Anseth, K. S., Biotechnology and Bioengineering (2009).
[3] Lanza R., Langer R., Vacanti J.P., Principles of Tissue Engineering: Fourth Edition, Elsevier (2013).
[4] Cui X, Gao G, Qiu Y. Accelerated myotube formation using bioprinting technology for biosensor applications. Biotechnol Lett. (2013).
[5] Ngan F. Huang, Shyam Patel, Rahul G. Thakar et al. Myotube Assembly on Nanofibrous and Micropatterned Polymers. (2006).
[6] An J, Teoh JEM, Suntornnond R, Chua CK. Design and 3D Printing of Scaffolds and Tissues. Engineering. (2015).
[7] Wiklund M. Acoustofluidics 12: Biocompatibility and cell viability in microfluidic acoustic resonators. Lab Chip. (2012).
Controlling the cell alignment and spacing is an essential of aspect of this project. Maintaining a uniform alignment throughout the continuously extruding fibre can be achieved by proper characterisation of the device by studying the acoustic mode shapes.
To this end we will:
• Create a 2D COMSOL simulation of the glass-teflon hybrid acoustic channel. • Compare the experimental observations to the simulation results. • Perform a parametric study to compare the effect of different fluid medium (corresponding to different hydrogel precursors) on the acoustic modes and expected forces on the cells. • Validate the results by using particle tracking velocimetry for calculating the forces experienced by the cells in experiments. • If time permits, this simulation will then be extended to 3D.
Other potential student projects: 1. Developing the next generation of cell alignment devices 2. Hydrogel characterisation and optimisation for tissue mimics
Controlling the cell alignment and spacing is an essential of aspect of this project. Maintaining a uniform alignment throughout the continuously extruding fibre can be achieved by proper characterisation of the device by studying the acoustic mode shapes.
To this end we will:
• Create a 2D COMSOL simulation of the glass-teflon hybrid acoustic channel. • Compare the experimental observations to the simulation results. • Perform a parametric study to compare the effect of different fluid medium (corresponding to different hydrogel precursors) on the acoustic modes and expected forces on the cells. • Validate the results by using particle tracking velocimetry for calculating the forces experienced by the cells in experiments. • If time permits, this simulation will then be extended to 3D.
Other potential student projects: 1. Developing the next generation of cell alignment devices 2. Hydrogel characterisation and optimisation for tissue mimics