Industrialization of a perfusion bioreactor: Prime example of a non-straightforward process.

Bioreactors are essential enabling technologies for the translation of advanced therapies medicinal products from the research field towards a successful clinical application. In order to speed up the translation and the spread of novel tissue engineering products into the clinical routine, tissue engineering bioreactors should evolve from laboratory prototypes towards industrialized products. In this work, we thus challenged the industrialization process of a novel technological platform, based on an established research prototype of perfusion bioreactor, following a GMP-driven approach. We describe how the combination of scientific background, intellectual property, start-up factory environment, wise industrial advice in the biomedical field, design, and regulatory consultancy allowed us to turn a previously validated prototype technology into an industrial product suitable for serial production with improved replicability and user-friendliness. The solutions implemented enhanced aesthetics, ergonomics, handling, and safety of the bioreactor, and they allowed compliance with the fundamental requirements in terms of traceability, reproducibility, efficiency, and safety of the manufacturing process of advanced therapies medicinal products. The result is an automated incubator-compatible device, housing 12 disposable independent perfusion chambers for seeding and culture of any perfusable tissue. We validated the cell seeding process of the industrialized bioreactor by means of the Design of Experiment approach, whilst the effectiveness of perfusion culture was evaluated in the context of bone tissue engineering.

Bottom-up engineering of the surface roughness of nanostructured cubic zirconia to control cell adhesion.

Nanostructured cubic zirconia is a strategic material for biomedical applications since it combines superior structural and optical properties with a nanoscale morphology able to control cell adhesion and proliferation. We produced nanostructured cubic zirconia thin films at room temperature by supersonic cluster beam deposition of nanoparticles produced in the gas phase. Precise control of film roughness at the nanoscale is obtained by operating in a ballistic deposition regime. This allows one to study the influence of nanoroughness on cell adhesion, while keeping the surface chemistry constant. We evaluated cell adhesion on nanostructured zirconia with an osteoblast-like cell line using confocal laser scanning microscopy for detailed morphological and cytoskeleton studies. We demonstrated that the organization of cytoskeleton and focal adhesion formation can be controlled by varying the evolution of surface nanoroughness.