Ligament repair in the ankle for restoration of function: exploring the application of decellularised grafts.

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This PhD will combine novel experimental testing and imaging methods to examine the mechanical performance of ankle ligaments and a potential replacement biomaterial and identify potential tissue damage mechanisms. Use and development of unique in vitro testing equipment will examine the mechanical behaviour of individual ankle ligaments and their contribution to normal function. The multidisciplinary project will use advanced imaging to identify damage patterns in collagen structures within the tissues. Evaluation of the limitations of bony fixation in the ankle will lead to novel engineering approaches to address this complex clinical challenge.Research ObjectivesThe primary aim of this project is to investigate the potential of a decellularised graft for the repair of ankle ligament injury. This will be achieved through the following objectives:1) Characterisation of native ankle ligaments and their insertion points2) Understanding mechanisms of failure of ligaments in the joint a) Identify biological damage b) Understand resultant changes in mechanical properties3) Identification of required scaffold geometriesa) Alignment of ligament with respect to anatomy and biomechanical functionb) Need for tendon-only or composite bone-tendon scaffoldsc) Selection of suitable porcine ligamentous tissue 4) Investigation of suitable fixation methods5) Working with clinicians and patients to understand specific clinical needsBackgroundGlobally, there is a growing need for interventions to repair and replace diseased or damaged musculoskeletal tissues. A recent report by the World Health Organisation suggests that 20%-33% of people across the globe live with a painful musculoskeletal condition, with such conditions costing the US$ 213 billion in 2011. Many conditions in the foot and ankle impact significantly on mobility, pain and quality of life. Underlying disease and acute injury can cause functional changes in the foot and ankle. Chronic ankle instability (CAI) affects normal biomechanical function and is a factor in the development of up to 22% of ankle osteoarthritis (OA) cases. CAI is regarded as insufficiency in the lateral ankle ligament complex, usually caused by a single traumatic event or re-injury after initial trauma. New methods to treat CAI by repairing ligaments in the ankle could prevent or delay the onset of related OA and improve patient quality of life. Repair methods for CAI include anatomical (reattachment of the ligament) or non-anatomical (repair with another material, such as tendon) reconstruction. Damaged tissues in CAI may be reconstructed with donor tissue to restore normal function. Donor tissues can be from the patient (autograft) or a deceased donor (allograft). Donor cells within allografts can trigger an immune response, resulting in delayed healing or tissue rejection. Importantly, normal mechanical function is mediated by the tissue-specific extracellular matrix (ECM) and the cells themselves are not required. Decellularisation processes remove cells and cellular debris from the ECM. The resulting scaffolds provide structural and mechanical support without provoking an adverse immune response. A series of patented decellularisation processes (the Leeds approach) have been developed in the Institute of Medical and Biological Engineering at the University of Leeds. The Leeds approach involves developing a tissue-specific decellularisation process; the use of tissue-specific ECM ensures that the biological and biomechanical properties are appropriate for the application. A recently developed process produces a porcine bone-tendon scaffold which may be a suitable for ligament repair.This project will develop a detailed understanding of the properties of natural ligaments and their injury mechanisms, identify appropriate dimension and potential fixation methods for the scaffolds and identify potential failure mechanisms to build confidence in the scaffolds for CAI repair