PRECISION MANUFACTURING OF MICROENGINEERED COMPLEX JOINT IMPLANTS (JOINTPROMISE)

There is convincing evidence, in animal models and in humans, that deep osteochondral defects of the joint surface lead to a high rate of osteoarthritis (OA) over time. The disease process in OA, the most prevalent arthritic disease affecting 25% of the adult population, involves the entire joint affecting both the articular cartilage and the underlying bone. Hence it is crucial to consider the entire osteochondral unit as a target for repair. Tissue engineered implants could provide a solution for the regeneration of this type of defects and prevent the development of OA. This project aims to address this unmet clinical need by developing complex joint implants that will possess the spatially inbuilt biologic information for regenerating these challenging defects. Breakthroughs in organoid technologies have allowed the development of cartilaginous microtissue structures that can predictively execute regenerative programmes upon implantation. These microtissues can be used as building blocks for bottom-up 3D bioprinting of living joint implants. In order to be able to produce scaled-up implants containing at the same time a highly precise structure, integration of bioprinting technologies is needed. Moreover in order to cover rising clinical demand the whole manufacturing process, which is mostly manual today, will need to be automated adopting robotics, bioprinting and bioreactor technologies. In order to demonstrate implant feasibility and efficacy, large osteochondral defect repair will be studied in the minipig, a large animal model relevant to the patient. Taken together we strive to develop an automated, GMP-grade platform producing large, patterned and vascularised joint implants providing also a paradigm shift for generic automated manufacturing of organoid-based tissue implants. JOINTPROMISE paves the way for high-volume, affordable production of entire biological joints, addressing a major socioeconomic challenge of the European ageing society.