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

前十字韧带(ACL)断裂越来越普遍，特别是在生活方式更活跃的年轻人群中。如果不治疗，前交叉韧带损伤可能会导致半月板损伤和退行性变化，如骨关节炎，导致进一步的疼痛和损害，并增加关节疼痛的经济负担。目前，最常见的手术解决方案是用患者的自体移植物取代受损的前交叉韧带。同种异体移植是一种有吸引力的替代方案，因为它们消除了采集任何自体组织的需要，但可能会引起不良免疫反应。因此，脱细胞肌腱/韧带移植将是替代天然前交叉韧带的理想选择，而不存在自体移植或同种异体移植的任何缺点。我们已经成功开发了一种脱细胞猪腱支架，并显示出良好的体内再生能力。然而，目前漫长的脱细胞过程改变了肌腱细胞外基质的组成和结构，降低了生物力学性能。该项目将确定一种新的更短、优化的脱细胞过程是否会减少猪肌腱超微结构的变化，以及这是否会改善细胞渗透以及在动态生物力学环境中与肌腱支架的体外相互作用。这项跨学科的工作将由机械工程、生物医学科学、物理和天文学学院的学者领导，结合材料科学、组织工程和纳米结构表征领域的技能，将代表着对脱细胞生物支架及其再生潜力的当前理解的一步改变。

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 auto grafts 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.