Development of decellularised porcine osteochondral scaffolds as matrices for cell implantation

Osteoarthritis currently affects 8.75 million people in the UK alone. This can cause major issues for those living with the disease, such as immobility and pain, which are often accompanied with psychological distress due to a loss in quality of life. One cause of osteoarthritis is damage to the articular cartilage which triggers inflammation and progressive degeneration. Early intervention strategies are employed to prevent disease progression such as microfracture, mosaicplasty and more recently autologous chondrocyte implantation. However, these all have their limitations in either, insufficient quality of repair material, donor site morbidity or limited biomechanical function prior to tissue regeneration.
This study first aimed to investigate the applicability of decellularised porcine osteochondral scaffolds in the treatment of large shallow cartilage lesions. This project built upon previous work, with an aim of enhancing these scaffolds through application with chondrocytes and self-assembling peptide hydrogel with chondroitin sulphate (P11-8/CS) incorporated. The hypothesis was that the resultant scaffold would be an ideal tissue replacement due to the retained native extracellular matrix structure, the increased regenerative potential offered by the cells and the enhanced biomechanical function from the addition of SAP-CS. These benefits, would ideally allow faster restoration of the healthy biomechanical function of the joint. Potential for cost-effectiveness versus matrix assisted chondrocyte implantation was observed. The dimensions of the decellularised scaffolds were adapted to dimensions which are clinically appropriate for the treatment of large shallow lesions. The resultant decellularisation quality, cytocompatibility and mechanical properties were all conserved, despite larger dimensions. Following this, a recellularization process was established for these decellularised scaffolds based using lyophilisation to increase cell penetration. These scaffolds were evaluated in a natural knee joint simulation model, which indicated viability of recellularised chondrocytes at Day 7. Following this, the ability of the P11-8/CS hydrogel alone to support chondrocyte cell proliferation and survival over a 14-day timecourse was demonstrated, whilst chondrogenic gene expression of encapsulated primary porcine chondrocytes was shown. The lyophilisation method was then developed to deliver SAP-GAG to the osteochondral scaffolds, which showed a trend for improved biomechanical properties.
Overall, this work has shown the potential for both recellularised decellularised scaffolds and self-assembling peptides, as devices to support chondrocyte implantation to aid the regeneration of large shallow cartilage lesions and early stage lesions respectively.