Generating durable and resilient repair of cartilage defects using tissue-specific adult stem cells - a systematic, therapeutic approach

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Osteoarthritis is the single largest cause of physical disability in the world, and yet, there are no clinically effective treatments to restore normal, pain-free movement of affected joints. Osteoarthritic lesions begin as small isolated cartilage defects that spread across the joint, if these defects can be repaired, an excellent opportunity exists to restore function and prevent further disease. For the past two decades tissue engineers have used a trial and error approach to repair cartilage defects, using an increasing and ingenious variety of scaffolds and cells with little regard to the normal growth mechanisms of articular cartilage. The sum of this approach is that this field of research has not moved significantly forward since its inception some 25 years ago. The method of transplanting cells into joints has inherent weaknesses that cannot be improved. The National Institute of Clinical Excellence UK guidelines state current transplantation methods do not provide long-term clinical effectiveness for patients nor are they cost-effective solution for short-term benefit. Our approach will break the status quo as it addresses and provides concrete solutions to the major problems that have thus far hindered progress. The major stumbling block to progress has been the lack of suitable cells to restore normal cartilage in joints. Stem cells are critical components in any solution to repair damaged joints, and the discovery of adult stem cells in articular cartilage and their ability to make new permanent cartilage has been an important advance. A problem when using stem cells is that the tissue they produce is immature - immature cartilage does not have the same properties as adult cartilage and is consequently prone to failure. A major recent achievement has been to understand what factors are required to convert immature cartilage into one that has adult properties. The critical question is, can we make new cartilage using stem cells, then transform it so that it is as stiff and durable as adult cartilage to provide a fully functional implant to restore pain-free movement in damaged joints? Our solution is to use 3D bio-printing in combination with cartilage stem cells to make new cartilage. Bioprinting allows us to make complex structures precisely, quickly and reproducibly, maximising the growth potential of stem cells to produce larger and thicker implants. We will then transform the engineered tissue so that it functions like adult cartilage before implanting it into the patient for preclinical testing. This approach is simple and emulates the same biological processes that occur in the body to produce durable and resilient articular cartilage in a highly accelerated and controlled manner. It also provides a clear pathway to systematically translate recent advances in cartilage biology and biofabrication into patient benefits. Given the scope of the challenge we have tailored our approach to be automated and scalable, offering the real potential to treat thousands rather than the few. The team assembled to accomplish this goal is multidisciplinary, highly focused and leading experts in each particular aspect of the solution.