The large-scale production of cells is a mandatory step to set up economically viable in vitro experimental models for basic research, disease modelling and drug testing, and to definitely translate tissue engineering and regenerative medicine strategies to the clinical practice for therapeutic applications. However, scalability and standardization in cellular manufacturing processes are still major challenges. In particular, when large numbers of cells are required, conventional two-dimensional (2D) culture strategies, mainly based on manual, extremely space- and labour-intensive interventions, are practically and financially unsustainable. For these reasons, methods providing a 3D suspension culture environment, mimicking the micro- environment of the cellular niche, have been widely adopted in industrial biotechnology for: (i) scalable and controlled expansion of stem cells and cancer cells; (ii) guiding stem cell differentiation; (iii) production of cellular spheroids and tissue-like constructs. Nowadays, dynamic suspension culture for scalable production and differentiation of cells is mostly performed by stirred tank and rotating bioreactors. Such devices are designed for providing a 3D homogenous culture environment, and for enabling monitoring and control of culture parameters, leading to more reproducible, robust and cost-effective processes. However, most of these bioreactors still suffer from critical issues, limiting the upscaling and the standardization of the expansion bioprocesses. Concerning stirred tank bioreactors, their performance can be affected by (i) collisions of the cells with the impeller and (ii) the onset of turbulent flow, that both can induce non-physiological mechanical and hydrodynamic-shear stresses on the cells and lead to cell damage. Moreover, these unfavourable conditions can affect cell growth rate and metabolism, interfere with stem cell pluripotency, and limit efficiency and reproducibility of the culture process. Rotating bioreactors generate a low-shear stress culture environment, allowing to partially overcome the limitations of stirred tank devices. However, the complexity of the technological solutions adopted for rotation make these devices not easily scalable and unsuitable for continuous medium replacement and real-time monitoring.
Cell culture is a key activity for research centers, biotech companies and hospitals. Several culture methods are applied, the simpler and more widespread being Petri capsules. More advanced methods are based on bioreactors, available in different categories varying in operation principles, size and cell culture application. As anticipated, SUSPENCE belongs to the category of dynamic suspension bioreactors.
Compared to the conventional practices, based on manual cell culture activities subject to high variability and hardly scalable for large scale cell production, dynamic suspension bioreactors offer higher efficiency, security, scalability, process standardization and monitoring.
The key objective of the Phase I project is the development of a detailed Business Plan, including market analysis and commercialization, technical and economic feasibility assessment and plans for product validation, business development, dissemination, contractual and IPR protection framework, commercialization agreements, forecast profit and loss, financial indicators and ROI estimations.
