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Lumios: Engineering high-throughput muscle tissues for drug development research
In the tissue engineering & biofabrication lab, we have developed a new bioprinting technology that enables the production of highly anisotropic, microstructured hydrogels and facilitates the cultivation of aligned tissues such as skeletal muscle or nerves. On this basis, we are currently working towards establishing the ETH Spin-off Lumios. In a previous proof-of-concept study, we were able to show that embedding myoblasts into these scaffolds, 14 days later, led to the formation of functional mini-muscles that showed similar contractile and biochemical properties as we see in native muscle tissues. Based on these promising results, we now want to integrate these tissues into a platform that enables their culture and characterization in a multi-well plate format and makes them accessible to drug development research for muscle-related diseases like myocardial infarction necrosis, sarcopenia or Duchenne muscular dystrophy.
Muscle tissue represents around 75% of the human body mass and is involved in all kinds of movements from running to the transport of food through the intestine all the way to moving your eyes as you are reading through this advertisement. One feature that separates muscle from other tissues in the human body is its anisotropy as it is characterized by highly aligned structures on the macro- (fascicles and myofibers), micro- (myotubes) and nanolevels (actin/myosin). Thus, in order to create functional muscle tissue in a tissue engineering context, replicating this intricate organization of extracellular matrix and cells is absolutely critical which none of the currently available biofabrication techniques has been able to achieve.
Filamented Light (FLight) biofabrication[1] is a patented technique that overcomes this limitation by creating scaffolds containing highly aligned hydrogel filaments with micrometer-diameter that can very effectively guide encapsulated cells to align and connect with each other to enable contractility of the whole muscle tissue. By treating the resulting muscle tissues with different toxins or regenerative drugs, we could also prove the viability of our system for in vitro drug development research. Within the student project, we aim to integrate these tissues into a standardized setup that allows for the high-throughput evaluation of different biochemical and functional properties (e.g., contraction force of muscle constructs) as a response to different treatments.
The project will concretely comprise the following tasks:
1. Familiarization with FLight bioprinting and the requirements for muscle tissue engineering
2. Design, manufacturing and evaluation of different accessories to enable high throughput printing of muscle tissues onto a deformable PDMS frame[2]
3. FLight bioprinting of muscle constructs and image-based analysis of contractile forces[3]
4. Evaluation of contractile forces before/after the treatment with different degenerative/regenerative molecules
**Your Background**
- Strong interest in translational biomedical research
- Cell culture experience
- Basic knowledge of CAD and FDM/DLP printing
- Experience with microscopy (e.g., Immunofluorescent staining)
- Experience with antibody-based biochemical assays (e.g._ WB, ELISA) is a plus
- Interest in entrepreneurship and spinoffs not required but a plus
- A master thesis project (6 months) is preferred.
**References**
[1] Liu, Hao, et al. "Filamented Light (FLight) Biofabrication of Highly Aligned Tissue‐engineered Constructs." Advanced Materials 34.45 (2022): 2204301. [2] Madden, Lauran, et al. "Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs." elife 4 (2015): e04885. [3] Hinds, Sara, et al. "The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle." Biomaterials 32.14 (2011): 3575-3583.
Muscle tissue represents around 75% of the human body mass and is involved in all kinds of movements from running to the transport of food through the intestine all the way to moving your eyes as you are reading through this advertisement. One feature that separates muscle from other tissues in the human body is its anisotropy as it is characterized by highly aligned structures on the macro- (fascicles and myofibers), micro- (myotubes) and nanolevels (actin/myosin). Thus, in order to create functional muscle tissue in a tissue engineering context, replicating this intricate organization of extracellular matrix and cells is absolutely critical which none of the currently available biofabrication techniques has been able to achieve.
Filamented Light (FLight) biofabrication[1] is a patented technique that overcomes this limitation by creating scaffolds containing highly aligned hydrogel filaments with micrometer-diameter that can very effectively guide encapsulated cells to align and connect with each other to enable contractility of the whole muscle tissue. By treating the resulting muscle tissues with different toxins or regenerative drugs, we could also prove the viability of our system for in vitro drug development research. Within the student project, we aim to integrate these tissues into a standardized setup that allows for the high-throughput evaluation of different biochemical and functional properties (e.g., contraction force of muscle constructs) as a response to different treatments.
The project will concretely comprise the following tasks:
1. Familiarization with FLight bioprinting and the requirements for muscle tissue engineering 2. Design, manufacturing and evaluation of different accessories to enable high throughput printing of muscle tissues onto a deformable PDMS frame[2] 3. FLight bioprinting of muscle constructs and image-based analysis of contractile forces[3] 4. Evaluation of contractile forces before/after the treatment with different degenerative/regenerative molecules
**Your Background**
- Strong interest in translational biomedical research - Cell culture experience - Basic knowledge of CAD and FDM/DLP printing - Experience with microscopy (e.g., Immunofluorescent staining) - Experience with antibody-based biochemical assays (e.g._ WB, ELISA) is a plus - Interest in entrepreneurship and spinoffs not required but a plus - A master thesis project (6 months) is preferred.
**References**
[1] Liu, Hao, et al. "Filamented Light (FLight) Biofabrication of Highly Aligned Tissue‐engineered Constructs." Advanced Materials 34.45 (2022): 2204301. [2] Madden, Lauran, et al. "Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs." elife 4 (2015): e04885. [3] Hinds, Sara, et al. "The role of extracellular matrix composition in structure and function of bioengineered skeletal muscle." Biomaterials 32.14 (2011): 3575-3583.