Developing a humanoid bioreactor for tendon tissue engineering

Tendon diseases, like other musculoskeletal disorders, represent a growing social and economic burden as our population is aging. They often result in tears, causing pain and disability. Surgical repairs are performed at an increasing rate but patient's outcomes are not promising, with 40% of repairs failing at the shoulder joint due to poor tissue healing. Patients with major tissue loss have particularly little chances of recovering. A promising repair strategy is the use of engineered tendon grafts. Tissue engineering involves the development of bioreactors that generate tendon tissue in vitro using the patient's cells, scaffolds and mechanical stimulation. However, more advanced bioreactors are needed to provide functional tendon grafts. Current bioreactors mostly provide uniaxial cyclic loadings, while evidence suggests that they should provide multiaxial stresses, similar to those found physiologically. In this context, musculoskeletal humanoid robots have the potential to apply realistic stresses. These robots replicate the inner structures of the human body such as muscles, tendons and bones. They have seen major developments in recent years, making it now possible to consider their use for unexplored applications in medicine. The aim of this research project is to investigate the potential of using musculoskeletal humanoid robots as a platform for musculoskeletal tissue engineering and in particular for tendon engineering. The overall hypothesis is that humanoid robots will enable the provision of physiological mechanical stimulation and that, as a result, they will lead to engineered tendons that are more functional than those produced with current stretch bioreactors. To demonstrate this, we are proposing to: (1) design a flexible bioreactor chamber compatible with musculoskeletal humanoids, (2) adapt an existing humanoid shoulder for our tendon engineering applications, (3) define the loading regimes of the humanoid bioreactor based on shoulder rehabilitation exercises, (4) produce tendon constructs with the novel system and demonstrate improvements compared to current bioreactors. Computational modelling and motion analysis will be used to support our work. This pioneering project is a step towards functional and personalised grafts to improve patient outcomes and reduce costs to the society.

Shoulder pain caused by rotator cuff tendon tear is responsible for prolonged periods of disability, absence from work and inability to carry out even basic household activities. Rotator cuff tendon tears are found in around 15% of 60 year olds, 25% of 70 year olds and 30% of 80 year olds. With the aging population and increased participation of the elderly in the labour force, their burden has become even more important. A recent study on health economics of rotator cuff estimated that successful repair would result in lifetime societal saving of $3.44 billion in the U.S. alone.

Approximately 10,000 of these rotator cuff tendon operations are carried out in the UK every year at a cost to the NHS of around £6800 per operation. However, conventional surgical repair (typically using sutures and anchors) still results in around 40% of failure. For patient with major tissue loss or experiencing a re-tear, conventional repair failure rates are even higher and, instead, tendon autograft transplantation may be performed. However, despite encouraging results, this approach remains rare mainly due to concern related to donor-site morbidity.

A regenerative medicine solution that provides engineered tendon grafts fabricated in vitro with the patient's cells would eliminate this main concern and would provide a reliable source of autografts for patients suffering either from a partial tear or from a large tears involving major tissue loss. The potential benefit to patients may include reduction of current failure rate of tissue repair, faster recovery and better tissue healing.

While current bioreactors used for fabricating engineered tendon have shown great potential, so far they have failed to produce grafts that are clinically relevant. This is in part because of the inadequate mechanical stimulation that they provide and the unsuitable dimensions of the constructs. In this context, humanoid musculoskeletal robots become relevant as they have the potential to closely mimic both the structure and the movements of the patient's body and thus to provide physiological mechanical stimulation to the tissue constructs. If the approach is proven to be promising, the long-term results of this research might lead to engineered grafts with improved functionality that are clinically relevant.

This may provide a long-term solution for the repair of the rotator cuff, which would translate into safer and more cost-effective patient care. But it could also have widespread applications for the repair of other musculoskeletal tissues including other tendons, ligaments, meniscus, and even cartilage and bone. A reliable and unlimited source of autografts is sought in a vast array of clinical areas and therefore the approach proposed here could potentially offer great benefits to patients through improved treatment for many conditions.