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The manufacturing of a biological tissue: REgeneration of the JOINt by Developmental engineering.

Final Report Summary - REJOIND (The manufacturing of a biological tissue: REgeneration of the JOINt by Developmental engineering.)

Regenerative Medicine has provided new methodologies to repair damaged tissues. Novel (stem) cell based approaches are under clinical development and some have entered clinical practice such as autologous cartilage cells for joint surface repair. However, the achievements in the clinics have been limited due to a number of reasons including the lack of manufacturing processes for the production of living 3D tissues and the need to develop new enabling technologies to achieve this.

REJOIND has generated biological cartilage tissue intermediates in a robust fashion using a
bio-inspired approach also termed “Developmental Engineering”, essentially mimicking nature. Proof-of-principle for this more sophisticated engineering approach that leads to the in vitro manufacturing of provisional tissues, in this case growing bones and joints, has been convincingly demonstrated.

Major goals have been achieved including:
1. The selection and expansion of proper stem cell populations with technologies to monitor these processes. In addition, very promising iPS technology has been developed providing the hope for access to an unlimited number of cells “off the shelf” for successful tissue engineering.
2. Culture conditions and bioreactor settings leading to robust differentiation of cartilage cells and microtissues at different degrees of maturation, providing the potential building blocks for skeletal tissue assembly.
3. Development and optimization of new enabling technologies, including MyCellHub software for process optimization, new bioreactors, non-invasive contrast enhanced nano-CT imaging and improved in silico modeling approaches.
4. The in vitro production of osteochondral-like tissues, which are capable of producing bone and cartilage ectopically and behave orthotopically as either osteochondral units or bone forming units. These findings set the stage to further improve the design of osteochondral implants with specific attention to the generation and maintenance of a highly specialized articular joint surface, and pave the way towards building a biological joint.