Abstract

The clinical impact of cell based therapeutic approaches for applications in the field of tissue regeneration is still limited.  Therefore,  more insight is needed on many aspects of the development of these novel cell based therapeutic medicinal products including a mechanistic understanding of cell survival, local inflammatory processes, tissue formation and tissue integration in vivo.
Manufacturing of the cell based implants and upscaling is another major challenge. In order to address this, we introduced a “developmental engineering” approach for the fabrication of clinical size products. This methodology is based on the design of sequential in vitro sub-processes corresponding to in vivo developmental stages.  They follow a gradual and coordinated progression of cell growth, differentiation and tissue assembly that leads to organization of cells into intermediate tissue forms. New enabling technologies are required to translate this into robust manufacturing  processes and include miniaturization, automation, bioreactor and biosensor technologies with online monitoring and non invasive imaging. In addition, the reduction of cost of production becomes a major goal.
Based on progress on many fronts, a  second wave of new and more rational approaches for tissue engineering  will hopefully lead to more predictable clinical outcomes.  In view of this,  a regulatory framework has been defined both in Europe and the USA in which tissue engineered products can prove their safety and effectiveness. For these products, to live up to the standards of drug development, challenges arise towards practical implementation but also to legislation and ethics.