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 language | English |
---|---|
Article number | e12653 |
Number of pages | 14 |
Journal | Cell Proliferation |
DOIs | |
Publication status | Published - 6 Sept 2019 |
Keywords
- tissue engineering
- osteochondral
- large animal study
- cartilage repair
- manufacturing
- Bioreactor