Innovative manufacturing of decellularised bone scaffolds

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Musculoskeletal disorders are the second greatest cause of disability in the UK. For example, one third of people aged over 45 have sought treatment for osteoarthritis, costing the NHS over £5 billion per year.Diseases such as cancer or trauma through mechanical insult can lead to damage of the skeletal structures requiring surgical intervention. Graft materials are used to replace and restore the function of musculoskeletal tissues including bone, cartilage, menisci and tendons.In iMBE we have developed decellularised musculoskeletal tissue scaffolds from both human and animal tissues to address a range of clinical grafting needs. Decellularised scaffolds are advantageous over traditional human and animal grafts, as removal of cellular components renders the graft immune-compatible. The advantage over synthetic grafting materials is the retention of the native tissue composition, structure and function which acts as the optimal environment for regenerative stem and progenitor cells. Decellularised bone has the potential to repair bony defects, but also to act as a skeletal attachment site when incorporated into composite bone-soft tissue scaffolds for example in a bone-tendon graft for cruciate ligament reconstruction. Decellularised bone and tendon products have been shown to function as excellent regenerative scaffolds in large animal studies. Although appropriate to produce tissues in the research setting, the current decellularisation processing methods for bony tissues are not compatible with scale up for industrial manufacture and therefore prove a real barrier to the use of these scaffolds clinically in patients. Also, one size does not fit all; a range of decellularised bone grafts with differing properties is required to match with orthopaedic application, surgeon preference, and patient variability. The research challenge is to develop improved industry-compatible methods of bone decellularisation and to elucidate the biological and biomechanical variance in the end product that can be achieved through altering different bioprocess parameters. The specific research questions are:1. Can the manufacturing bioprocess be adapted to good manufacturing process (GMP) standards appropriate for clinical grade scaffold production at NHS BT facilities? 2. Can variation of the source tissue, storage and sterilisation method lead to a stratified range of decellularised bone products?This project will involve biological, biomechanical and CT analysis of bone along with the product design challenge of building a device to partly automate the bioprocess.This research has the potential to directly impact on industry practice and also contribute towards the production of improved decellularised scaffolds for use in bony tissue regeneration. Aim: To produce and characterise a range of decellularised bone products using industry compatible manufacturing processes to a standard suitable for clinical use.Objectives (manufacturing):1. To physically remove bone marrow in a way compatible with working in a grade B clean room.2. To develop a rig/device to contain and automate the tissue washing process.3. To reduce the duration of the decellularisation bioprocess.The manufacturing process will initially be optimised using porcine tissue prior to application to human tissue.Objectives (product variation):1. To determine the effect of the following parameters on resultant biological, material and biomechanical properties of the human bone scaffold.a. The size and shape of bone blocks which are processedb. The storage method used e.g. frozen vs lyophilisedc. The sterilisation method used e.g. irradiation vs chemical sterilisation This project will use decellularisation, histology, cell culture and biochemical assay facilities in FBS. Micro CT imaging and biomechanical testing facilities will be used in the school of mechanical engineering.