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Hydrogel characterisation and optimisation for tissue mimics
In this project we aim to identify better native matrix mimics to promote cell viability and proliferation. We will also study how spatial organisation of cells can affect the cell growth.
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.
One of the essential aspects of this project is to identify better native matrix mimics to promote cell viability and proliferation. Synthetic hydrogels are widely used as a blank slate material to reproducibly mimic the native extracellular matrix. To this end, we will:
• Study different synthetic hydrogels and analyse their interaction with cells like fibroblasts, tenocytes or myocytes.
• Compare cell growth, viability, and metabolic activity in different hydrogels with varying compositions.
• Measure the gelation rates and stiffnesses of photopolymerisable gels using a photo-rheometer.
• Based on the results, extrusion of these gels through the acoustofluidic setup will be studied.
• Compare cell growth in aligned and unaligned cells within hydrogel fibres.
• If time permits, external stimulation could be used to induce movement in fibre with aligned muscle cells.
• Tensile testing of the formed fibers to mechanically characterise these fibres.
Other potential student projects:
1. Developing the next generation of cell alignment devices
2. Simulation and experimental characterisation of acoustic devices
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.
One of the essential aspects of this project is to identify better native matrix mimics to promote cell viability and proliferation. Synthetic hydrogels are widely used as a blank slate material to reproducibly mimic the native extracellular matrix. To this end, we will: • Study different synthetic hydrogels and analyse their interaction with cells like fibroblasts, tenocytes or myocytes. • Compare cell growth, viability, and metabolic activity in different hydrogels with varying compositions. • Measure the gelation rates and stiffnesses of photopolymerisable gels using a photo-rheometer. • Based on the results, extrusion of these gels through the acoustofluidic setup will be studied. • Compare cell growth in aligned and unaligned cells within hydrogel fibres. • If time permits, external stimulation could be used to induce movement in fibre with aligned muscle cells. • Tensile testing of the formed fibers to mechanically characterise these fibres.
Other potential student projects: 1. Developing the next generation of cell alignment devices 2. Simulation and experimental characterisation of acoustic devices
Dhananjay Deshmukh (deshmukd@ethz.ch)
Prof. Mark Tibbit (mtibbitt@ethz.ch)
Dhananjay Deshmukh (deshmukd@ethz.ch) Prof. Mark Tibbit (mtibbitt@ethz.ch)