Bioreactor-manufactured cartilage grafts repair acute and chronic osteochondral defects in large animal studies
ukasovic A, Asnaghi MA, Kostesic P, Quasnichka H, Cozzolino C, Pusic M, Hails L, Trainor N, Krause C, Figallo E, Filardo G, Kon E, Wixmerten A, Maticic D, Pellegrini G, Kafienah W, Hudetz D, Smith T, Martin I, Ivkovic A, Wendt D.
Objectives: Bioreactor-based production systems have the potential to overcome limitations associated with conventional tissue engineering manufacturing methods, facilitating regulatory compliant and cost-effective production of engineered grafts for widespread clinical use. In this work, we established a bioreactor-based manufacturing system for the production of cartilage grafts.
Materials & methods: All bioprocesses, from cartilage biopsy digestion through the generation of engineered grafts, were performed in our bioreactor-based manufacturing system. All bioreactor technologies and cartilage tissue engineering bioprocesses were transferred to an independent GMP facility, where engineered grafts were manufactured for two large animal studies.
Results: The results of these studies demonstrate the safety and feasibility of the bioreactor-based manufacturing approach. Moreover, grafts produced in the manufacturing system were first shown to accelerate the repair of acute osteochondral defects, compared to cell-free scaffold implants. We then demonstrated that grafts produced in the system also facilitated faster repair in a more clinically relevant chronic defect model. Our data also suggested that bioreactor-manufactured grafts may result in a more robust repair in the longer term.
Conclusion: By demonstrating the safety and efficacy of bioreactor-generated grafts in two large animal models, this work represents a pivotal step towards implementing the bioreactor-based manufacturing system for the production of human cartilage grafts for clinical applications. Read the Editorial for this article on doi:10.1111/cpr.12625.
Keywords: bioreactor; cartilage repair; large animal study; manufacturing; osteochondral; tissue engineering.
PMID: 31489992 PMCID: PMC6869519 DOI: 10.1111/cpr.12653
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