Collaborators Week: Cartilage regeneration in knees

Our work on cartilage regeneration began over a decade ago in collaboration with Prof Peter Choong based at St Vincent’s Hospital, Melbourne. Most of the early brain storming sessions revolved around Peter and I having predawn coffees in Melbourne. Peter’s detailed insights into the need provided the framework for our challenge and the caffeine spurred what may have been considered a crazy idea or two.

We combined his team’s knowledge, at the time, on stem cell biology and clinical deployment with our?latest breakthroughs in biomaterials science and advanced fabrication to make significant progress. In particular, we developed a novel bioink and a Biopen (Axcelda) device that protected the living cells during delivery and promoted?proliferation and differentiation into cartilage.

Prof Claudia De Bella joined our team from the Rizzoli Orthopaedic Institute of Bologna. Claudia brought new knowledge and insights as well as additional energy to the team. Subsequently, through Claudia’s connections, Dr Carmine Onofrillo and Dr Serena Duchi also from the Rizzoli Institute joined the team. Their input was to prove pivotal in developing cell isolation and processing protocols relevant to deployment in the clinic.

We discovered that there was a need for innovation in all steps of the process from adipose tissue harvesting to cell processing, bioink formulation and the delivery device.

As we pushed the project towards translation together, we learnt much about IP protection, regulation, certification and commercialisation. We certainly learnt that our scientific?and clinical teams could not cover all those bases – we did not have the skills. So, together we have built a more extended collaborative network to push towards translation. This has enabled us to attract Medical Research Future Fund (MRFF) funding for the Axcelda project and this will give us a real tilt at success!

“The Axcelda project enabled us to make impact as a multidisciplinary collaborative team and challenged us to tackle one of the biggest societal burden’s, namely, osteoarthritis (OA) which costs our community over $5 billion dollars a year.

“Axcelda enhanced our focus by not simply looking to a better way to treat osteoarthritis, but brought the most innovative minds from the bench and bedside together to drive an ambitious programme to STOP OA from the beginning. We are excited by our achievements and the framework for research we have developed which will act as a platform for others who are looking for bioengineering solutions to treat human disease,” - Prof Peter Choong, St Vincent’s Hospital

We have learnt much from each other and now we can see the path towards first in human trials ahead of us. This would not have been possible without the input of all the many skills over an extended period of time. This functional, fully integrated collaborative team never waivered from our ultimate goal – cartilage regeneration in knees – using a clinically deployable technology.

?

Selected Publications

• Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold, Ye, K., Felimban, R., Traianedes, K., Moulton, S.E., Wallace, G.G., Chung, J., Quigley, A., Choong, P.F.M., Myers, D.E. PlosOne 2014, 9 (6), e99410 (1-9).
• Development of the Biopen: A handheld device for surgical printing of adipose stem cells at a chondral wound site, O’Connell, C.D., Di Bella, C., Thompson, F., Augustine, C., Beirne, S., Cornock, R., Richards, C.J., Chung, J., Gambhir, S., Yue, Z., Bourke, J., Zhang, B., Taylor, A., Quigley, A., Kapsa, R., Choong, P., Wallace, G.G. Biofabrication 2016 8, 015019.
• Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair, Duchi, S., Onofrillo, C., O’Connell, C.D., Blanchard, R., Augustine, C., Quigley, A.F., Kapsa, R.M.I., Pivonka, P., Wallace, G., Di Bella, C., Choong, P.F.M. Scientific Reports 2017, 7, 5837.
• Biofabrication of human articular cartilage: a path towards the development of a clinical treatment, Onofrillo, C., Duchi, S., O’Connell, C.D., Blanchard, R., O’Connor, A.J., Scott, M., Wallace, G.G., Choong, P.F.M., Di Bella, C. Biofabrication 2018, 10, 045006.
• Evaluation of sterilisation methods for bio-ink components: gelatin, gelatin methacryloyl, hyaluronic acid and hyaluronic acid methacryloyl, O’Connell, C.D., Onofrillo, C., Duchi, S., Li, X., Zhang, Y., Tian, P., Lu, L., Trengove, A., Quigley, A., Gambhir, S., Khansari, A., Mladenovska, T., O’Connor, A., Di Bella, C., Choong, P.F., Wallace, G.G. Biofabrication 2019, 11 (3), 035003.
• Free-form co-axial bioprinting of a gelatin methacryloyl bio-ink by direct in situ photo-crosslinking extrusion, O’Connell, C.D., Konate, S., Onofrillo, C., Kapsa, R., Baker, C., Duchi, S., Eekel, T., Yue, Z., Beirne, S., Barnsley, G., Di Bella, C., Choong, P.F., Wallace, G.G. Bioprinting 2020, 19, e00087.
• The regulatory challenge of 3D bioprinting, Mladenovska, T., Choong, P.F., Wallace, G.G., O’Connell, C.D. Regenerative Medicine 2023, 18 (8), 659-674.