Damaged articular cartilage joints (e.g. knee) are associated with loss of function and joint degeneration which can lead to osteoarthritis (OA) and the need for total joint replacement. For the treatment of small cartilage defects, conventional therapies e.g. microfracture and osteochondral autograft transplantation are used, but with limited success. An advanced biomaterial capable of restoring healthy joint function remains something of a ‘Holy Grail’. Developing a biomaterial-based solution for the repair of large joint damage presents a particularly complex challenge due to: (i) the complex zonal structure of the tissue (i.e. articular cartilage on top, an intermediate calcified cartilage layer, and underlying subchondral bone); (ii) difficulty in keeping a biomaterial in place in the joint; and (iii) challenges in directing stem cells to promote the formation of stable cartilage. Building on a wealth of experience in the area, we propose a solution. ReCaP will initially overcome the problems with traditional biomaterials approaches by utilising recent advances in the area of advanced manufacturing and 3D-printing to develop a 3D-printed multi-layered scaffold with pore architecture, mechanical properties and bioactive composition tailored to regenerate articular cartilage, intermediate calcified cartilage and subchondral bone. Following this, and building on internationally recognised pioneering research in the applicant’s lab on scaffold-mediated nanomedicine delivery, this system will be functionalised for the controlled non-viral delivery of nucleic acids (including plasmid DNA and microRNAs) to direct host stem cells to produce stable hyaline cartilage at the joint surface and encourage the rapid formation of vascularised bone in the subchondral region. A new paradigm-shifting surgical procedure will then be applied to allow this system to be anchored to the joint surface while directing host cell infiltration and tissue repair, thus promoting the restoration of even large regions of the damaged joint through a joint surfacing approach. The proposed ReCaP platform is thus a paradigm shifting disruptive technology that will revolutionise the way joint injuries are treated.
