The effects of decellularisation process optimisation on the structure-function relationship and mechanobiology of tendon

Rupture of the anterior cruciate ligament (ACL) is becoming increasingly prevalent, especially in younger populations with more active lifestyles. If left untreated, ACL injuries can lead to meniscus damage and degenerative changes such as osteoarthritis causing further pain and impairment, and increasing the economic burden of joint pain. Currently, the most common surgical solution is to replace the damaged ACL with autografts taken from the patient. Allografts are an attractive alternative as they eliminate the need to harvest any autologous tissue, but may elicit adverse immunological reactions. Hence, an acellular tendon/ligament graft would be ideally positioned to replace the native ACL without any of the disadvantages of autografts or allografts. We have successfully developed a decellularised porcine tendon scaffold, which has shown promising in-vivo regenerative capacity. However, the current lengthy decellularisation process alters the composition and architecture of the tendon extracellular matrix and reduces the biomechanical properties. This project will determine if a new shorter, optimised decellularisation process will reduce alterations to the porcine tendon ultrastructure and if this improves cell infiltration and interaction with the tendon scaffold in-vitro in a dynamic biomechanical environment. The interdisciplinary work will be led by academics in the Schools of Mechanical Engineering, Biomedical Science and Physics and Astronomy, combining skills in the areas of material science, tissue engineering and nanoscale structural characterisation and will represent a step change in the current understanding of decellularised biological scaffolds and their regenerative potential.