Globally, more than 11 million burn injuries occur every year and 180 000 of these are fatal. Bioengineered skin can be manufactured manually but the process is time-consuming and costly. During the past ten years, the environment has become primed for the development of new manufacturing processes and equipment. Automation is now a reality for industrialisation of tissue engineered products.
A new era for bioengineered skin
“At Cutiss through the denovoSkin project, we have been able to blend progress in engineering and biology to automate these manual processes,” explains Vincent Ronfard, chief innovation officer at Cutiss AG. The innovative process involves growing new skin from the body's own tissue. This saves lives, intends to reduce scarring in people with extensive skin injuries – and ultimately improves their quality of life. The basis behind autologous cellular therapy for large burn treatment is to multiply cells from a small-sized piece of skin tissue. This involves amplification – expanding the patient’s cells hundreds to thousands of times while preserving stemness and quality of the cells. This is a critical step in the manufacturing process when the ability of the cells to replicate and differentiate into viable cell lines is maintained. To multiply the cells, the team decided to adapt the hollow fibre technology developed by Terumo BCT. “We were able to partially succeed in producing a large number of cells in a short period of time with acceptable cell quality to manufacture our bioengineered skin,” explains Ronfard. This step will be integrated within upstream and downstream processes.
Unexpected issues resolved
At the start of the project, the team aimed to develop a single integrated device to automate their manufacturing process (fully integrated automation). Ronfard outlines the evolution of their system: “After several brainstorming sessions, we realised it was not the best approach. We then decided to break down the manual process and to divide it into three modules: cell isolation, cell expansion and tissue building.” Phase II will be the seamless integration of the three modules and their implementation using good manufacturing practices (GMP). After their successful development, some of the intermediate connections between modules still need to be optimised as well as the automation of in-process controls.
The future for denovoSkin
The global market for large burns treatment amounts to billions of dollars. denovoSkin™ is unique and supports scale-up. “Overall, we are very pleased with the result of the denovoSkin automation project. We have demonstrated the feasibility of the automation of the bioengineered skin manufacturing process, generated IP and know-how, and built two prototypes never developed before.” denovoSkin™ has also been granted Orphan Drug Designation for the treatment of burns by Swissmedic, the European Medicines Agency and the FDA. Ronfard continues: “We now have a solid basis to pursue this programme to completion and build a skin engineering machine to use in our manufacturing according to GMP rules.” The work on this final phase is anticipated to take three years. Ronfard concludes: “EU funding has allowed us to make solid advances in the automation of the manufacturing process in tissue engineering therapy. Further funding, in the region of EUR 15 million will allow us to develop this exceptional scientific breakthrough for affordable personalised skin grafting.”
denovoSkin, automation, bioengineered, burns, skin graft, skin manufacturing, stemness