Nanovibrational control of chondrogenic differentiation

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Cartilage has very low self-healing capacity as it has no blood supply. This means that damage is not repaired and gets worse with time. Arthritis arising from cartilage damage, osteoarthritis (OA), is a massive healthcare burden costing the UK £13B pa when considering healthcare and days lost from work. It can affect reasonably young people with one-third of 50-64-year-olds presenting with OA. Surgeons are very limited in the interventions they can use. They can clean up cartilage defects using keyhole surgery and this can provide some temporary pain relief. They can bring blood from the bone using drilling to encourage the cartilage cells (chondrocytes) to grow, but this results in poor quality cartilage with poor mechanical characteristics (fibrocartilage) and again is a temporary fix. They also have the option of using autologous chondrocyte implantation (ACI) or matrix-assisted ACI, MACI. Here lab-grown chondrocytes are implanted, engraft and form new cartilage. However, lab-grown chondrocytes are not the same as the chondrocytes that allow joint movement and the procedure is thus expensive with limited success. Typically, surgeons will just keep an eye on degeneration and patient pain until joint replacement becomes inevitable. This is a concern as we are an ageing population and increasingly outlive joint replacement lifetime resulting in replacement surgery with much worse outcomes. This leaves older people with pain and limited mobility resulting in physical and mental co-morbidities and reduced lifespan.We have developed a novel bioreactor that can manufacture lab-grown chondrocytes with the correct phenotype. The bioreactor uses tiny vibrations (30 nm applied 1000 times a second) to tell the patients' bone marrow stem cells to turn into the type of chondrocytes found at the articulating surface of joints. We have previously applied the bioreactor to bone cell therapies where we are preparing for a first human trial. Further, cell engraftment is much more successful if the cells are delivered with a supporting scaffold (i.e. in a material). We have developed injectable gels where we can control mechanical properties, degradability and add in little bits of signalling molecules that the chondrocytes like.Together, the technologies can provide an attractive route towards injectable cell therapies delivered via keyhole surgery that can facilitate cartilage regeneration. To address the massive problem of OA, we need to be able to intervene and regenerate and the optimal chondrocyte phenotype is hard to establish; our technologies will enable this.