Engineering skeletal muscle using a humanoid bioreactor platform

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. Muscle injuries and diseases are becoming more frequent as our population is aging, which causes an increasing societal and economic burden. As current repair strategies are not satisfactory, the awareness of the need for new repair approached is increasing in academia, in industry and also for end users.

Tissue engineering is a promising repair strategy for skeletal muscle. This approach 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 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). Musculoskeletal humanoids can replicate the inner structures, such as muscles, tendons or 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 aim is to determine the importance of physiologically-relevant mechanical stimulation and electrical stimulation for muscle tissue engineering. This will contribute to generating better quality muscle grafts. If such an approach is successful, it will provide a reliable and unlimited source of muscle autografts which would translate into safer and more cost-effective patient care.

To achieve this goal, a scaffold able to support skeletal muscle tissue growth will need to be developed, either through muscle decellularization or hydrogel approaches. The existing soft chamber of the humanoid bioreactor, currently employed for tendon tissue engineering, will be adapted to host the novel muscle scaffold, allowing both its mechanical and electrical stimulation. The impact of such stimulations on the colonization of the scaffold by skeletal muscle cells will be investigated. The functionality of the engineered muscles will then need to be evaluated.

This highly multidisciplinary project involves various aspects of bioengineering, biology, bioelectronics and biomechanics. Although the end application proposed here is to support the regeneration of large muscle defects, other areas in science could benefit from this project. The development of scaffold or biomaterials using this more physiological platform will be of significant interest to other researchers in the field of tissue engineering, as the strategy could be applied to other tissues. Additionally, this project will contribute to the development of bio-actuators, which would benefit developments in bio-robotics and soft robotics.