Background

Current tissue engineering paradigm

Despite the compelling clinical need to regenerate damaged tissues/organs, the impressive advances in the field of tissue engineering have yet to result in viable engineered tissue products with widespread therapeutic adoption. Manufacturing-related issues, including regulatory compliance, standardisation, up-scaling, and cost-effectiveness, have been proposed as central challenges to be addressed for the commercial success of a cell-based engineered product. In fact, the central bioprocesses for engineering cell-based grafts have traditionally been, and continue to be, based on conventional manual bench-top techniques, which due to the large number of manual and labour-intensive manipulations required, possess inherent risks of contamination, potential high intra- and inter-operator variability, limited scale-up opportunity, and high manufacturing costs in the long-term.

The BIO-COMET concept is for bioreactor-based manufacture of tissue grafts. Bioreactors have the potential to overcome the current limitations by:

  • providing a controlled physico-chemical culture environment, which tightly regulates the bioprocesses, minimising process and product variability;
  • including monitoring and data management systems which offer a high level of traceability and increased compliance to regulatory guidelines;
  • introducing automation which facilitates safe and standardised production methods and maximises prospective scale-up and cost-effectiveness in the long-term.

Cell therapy for cartilage repair

While there are a variety of causes of degenerative joint diseases, such as osteoarthritis in an ageing population, the onset of degeneration in nearly half of the cases has been associated with prior injuries to articular cartilage that have gone untreated. Autologous chondrocyte implantation (ACI), which is based on the injection of a suspension of chondrocytes into a cartilage defect, has been well-established in the clinic for the repair of cartilage injuries for nearly two decades. Although good clinical results are generally reported in short-term follow-up, the technique generates a repair tissue with inferior mechanical properties as compared to healthy cartilage, jeopardising a durable repair in the long-term.

As an alternative, a three-dimensional cartilage tissue graft, engineered in vitro to possess functional properties (i.e. to biochemically and mechanically mimic native cartilage), could reduce the initial rehabilitation time and result in a more durable repair in the long-term. The tools, technologies, and devices developed within BIO-COMET will enable the production of standardised functional cartilage grafts, and their assessment in pre-clinical and clinical models.