Tackling cartilage damage with 3D printing and gene therapeutics
Cartilage, the tissue that lines the surface of our synovial joints in our ankles, elbows, hips and knees, thins as we get older. Unlike bone, cartilage does not have the capacity to self-repair. “A major manifestation of this as we age is the onset of osteoarthritis,” says ReCaP project coordinator Fergal O’Brien from the Royal College of Surgeons in Ireland. “Surgeons might try to go in and clean things up, but the end result is often a hip or knee replacement.”
New approaches to treating cartilage damage
The ReCaP project, supported by the European Research Council, sought to develop new approaches to treating cartilage damage. It built on previous work to develop biomaterials that promote the regeneration of cartilage tissue. “We developed a biomaterial that mimics the structure of native cartilage,” adds O’Brien. “We did this by combining collagen, a protein found in lots of tissue, with other substances you’d find in cartilage. When implanted into small cartilage defects, the biomaterial acts like sponge, soaking up cells and directing them to repair damaged tissue.” While this solution might work for small defects, it was found to be insufficient in addressing more significant cartilage damage. This is where ReCaP comes in. “In this project, we improved the scaffold by 3D-printing a mechanically sound synthetic polymer,” explains O’Brien. “This was then impregnated with a softer natural polymer, so that the scaffold retains its biological functionality.” The project team then applied gene therapeutics. Nanoparticles are taken up by cells, which then switch certain genes on or off. “For example, genes that can help to produce new cartilage matrix are switched on, while genes associated with inflammation are switched off,” notes O’Brien.
Biomaterial for tissue repair
The project was successful in developing a biomaterial for tissue repair that delivers a gene therapeutic. This was tested in animals such as goats, and a paper on the results is currently under review. Some aspects of the technology are the subject of a submission to protect associated intellectual property. “We have recently secured more funding, and this will allow us to further explore the commercial potential of the platform,” says O’Brien. “We were very fortunate to be supported in this project by the ERC, which is very much focused on high-risk, high-gain research.” Possible options being analysed include partnering with a multinational company, or spinning out a start-up.
Addressing early-stage spinal cord injuries
O’Brien and his team are also currently looking into applying their findings to other tissues. Being able to address early-stage spinal cord injuries for example could have a huge impact on people’s lives. “Our idea here is to add an electrically active element to our 3D-printed material and deliver alternative gene therapeutics,” he explains. “This material would carry the gene therapeutic to switch certain cells on and off, but also carry electrical stimulation, opening up a whole new paradigm of potential applications.” The Irish Rugby Football Union Charitable Trust and the AMBER Centre are funding this research, and a number of injured former players are working with O’Brien and his team on this. Sporting unions around the world are beginning to take notice. “One of the players is writing a book about his experience of injury, and of being part of this work,” remarks O’Brien.
Keywords
ReCaP, cartilage, 3D printing, gene therapeutics, implants, inflammation, osteoarthritis
