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.
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).
Being an interdisciplinary project various aspects of the device, hydrogels and cell growth can be studied in a student project based on the interests and background of the student.
Acoustofluidic control on the alignment of cells depends on many factors, the source of the sound waves (ie. the piezoelectric transducer), the geometry of the fluidic channel, materials used, etc. In this project we will study the effect of these components to design the next generation of cell alignment devices.
To this end we will:
• Study acoustic modes for different dimensions of piezoelectric transducers.
• Study acoustic modes for multiple piezoelectric transducers.
• Study various coatings for the fluidic channel material.
• Quantify the limits of this technology in terms of viscosity of the hydrogel precursor, geometry of the fibre, speed of cell manipulation.
• Study the feasibility of using a self-healing hydrogel as a carrying material for such a system.
• Based on the results, the best possible combination of acoustofluidic device and hydrogel system will be tested for continuous production of hydrogel fibre with aligned cells.
• If time permits, this system could be tested by mounting onto a 3D printer.
Being an interdisciplinary project various aspects of the device, hydrogels and cell growth can be studied in a student project based on the interests and background of the student.
Acoustofluidic control on the alignment of cells depends on many factors, the source of the sound waves (ie. the piezoelectric transducer), the geometry of the fluidic channel, materials used, etc. In this project we will study the effect of these components to design the next generation of cell alignment devices. To this end we will:
• Study acoustic modes for different dimensions of piezoelectric transducers. • Study acoustic modes for multiple piezoelectric transducers. • Study various coatings for the fluidic channel material. • Quantify the limits of this technology in terms of viscosity of the hydrogel precursor, geometry of the fibre, speed of cell manipulation. • Study the feasibility of using a self-healing hydrogel as a carrying material for such a system. • Based on the results, the best possible combination of acoustofluidic device and hydrogel system will be tested for continuous production of hydrogel fibre with aligned cells. • If time permits, this system could be tested by mounting onto a 3D printer.