Engineering skeletal muscle using a humanoid bioreactor platform
LEAD SUPERVISOR: Professor Pierre-Alexis Mouthuy, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Co-supervisor: Professor Sarah Snelling, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Commercial partner: Devanthro GmbH, Munich, Germany
Skeletal muscle is the largest organ system in the body by mass and is necessary to generate forces for movement and locomotion. Unlike tendons and ligaments, muscle tissue can easily regenerate itself when subjected to minor injuries. However, irreversible loss of muscle tissue affects thousands of patients per year in the UK alone and can be caused by severe conditions such as myopathy, large trauma (e.g. blast injuries) and removal of cancer tissue. Failure of repair results in atrophy of muscle fibers, fibrosis, and fatty accumulation within and around the muscles.
Tissue engineering is a promising repair strategy for skeletal muscle. This involves the use of biomaterials, cells and bioreactor systems, the combination of which allow control of cell culture conditions to provide physical stimulation to the cell-biomaterial constructs to engineer muscle in vitro. Both mechanical and electrical stimulation are relevant to muscle tissue engineering and have been shown to improve the improve cell proliferation and differentiation.
Our research group has extensive experience of biomaterial development and testing, including use of decellularized biological tissues, hydrogels and electrospun materials. We have also recently developed a unique bioreactor system that uses a musculoskeletal (MSK) humanoid robotic arm to mimic the motion and forces observed at the human shoulder joint and actuate cell-biomaterial constructs (EPSRC-funded Humanoid Bioreactor project, EP/S003509/1) [1,2]. MSK humanoids can replicate the inner structures (muscles, tendons and bones) and the biomechanics of the human body using strings actuated by electric motors. To develop the humanoid bioreactor platform, we combined these robots with soft, flexible bioreactor chambers that host the cell-biomaterial constructs and maintain them alive for long periods of time. While our efforts have so far been focused on tendon tissue engineering for rotator cuff repair applications, the same platform can be applied to engineer skeletal muscle.
This PhD project will focus on applying the humanoid bioreactor system to skeletal muscle tissue engineering.
The main goals of the project include:
1) Adapt the hardware and software involved in Devanthro’s robotic arm platform to enable tissue engineering of supraspinatus muscle (or similar)
2) Develop a scaffold able to support skeletal muscle tissue growth (through muscle decellularization or hydrogel approaches).
3) Adapt the soft chamber design of the current humanoid bioreactor to host the novel muscle scaffold and integrate electrodes for electrical stimulation of the cell-biomaterial constructs.
4) Investigate the impact of mechanical and electrical stimulation on the (re)colonisation of the scaffold by skeletal muscle cells
5) Evaluate the functionality of the engineered muscles, including through the biological response and metrics (next generation sequencing transcriptomics), the biomechanical properties and the range of forces they can generate.
This is a highly multidisciplinary project that involves various aspects of bioengineering, biology, bioelectronics and biomechanics. Although the end application proposed here is to support the regeneration of large muscle defects, a potential outcome of the project is the generation of a new range of bio-actuators, which would benefit developments in bio-robotics and soft robotics.
[1] P.-A. Mouthuy, S. Snelling, R. Hostettler, A. Kharchenko, S. Salmon, A. Wainman, J. Mimpen, C. Paul, A. Carr, Humanoid robots to mechanically stress human cells grown in soft bioreactors, Communications Engineering 1(1) (2022) 2.
[2] Nature video: A robotic Petri dish: How to grow human cells in a robot shoulder https://www.youtube.com/watch?v=wd4YPsIh7h0
Apply using course: DPhil in Musculoskeletal Sciences
January 2023 update:
Applications for this iCASE project (for October 2023 entry) are no longer accepted.
