Bioreactor manufactured cartilage grafts repair acute and chronic osteochondral defects in large animal studies

Andreja Vukasovic, M Adelaide Asnaghi, Petar Kostesic, Helen L Quasnichka, Carmine Cozzolino, Maja Pusic, Lauren Hails, Nuala Trainor, Christian Krause, Elisa Figallo, Giuseppe Filardo, Elizaveta Kon, Anke Wixmerten, Drazen Maticic, Graziella Pellegrini, Wael Kafienah, Damir Hudetz, Tim Smith, Ivan Martin, Alan IvkovicDavid Wendt

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
172 Downloads (Pure)

Abstract

Bioreactor-based production systems have the potential to overcome limitations associated with conventional tissue engineering manufacturing methods, facilitating regulatory compliant and costeffective production of engineered grafts for wide-spread clinical use. In this work, we established a bioreactor-based manufacturing system for the production of cartilage grafts. All bioprocesses, from cartilage biopsy digestion through the generation of engineered grafts, were performed in our bioreactorbased 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. The results of these studies demonstrate the safety and feasibility of the bioreactorbased 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. By demonstrating the safety & efficacy of bioreactor-generated grafts in two large animal models, this work represents a pivotal step towards implementing the bioreactorbased manufacturing system for the production of human cartilage grafts for clinical applications.
Original languageEnglish
Article numbere12653
Number of pages14
JournalCell Proliferation
DOIs
Publication statusPublished - 6 Sep 2019

Keywords

  • tissue engineering
  • osteochondral
  • large animal study
  • cartilage repair
  • manufacturing
  • Bioreactor

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