The pharmaceutical industries face to a major issue, which is a very high failure rate in drug discovery, with 90% of failure in clinical trials. The central nervous system is particularly concerned, with an involvement in 30% of safety failure in clinical trials, but only in 7% in preclinical trials (Cook et al. 2014). That point a lake of relevance of preclinical models.
Preclinical models are both in vitro and in vivo models. The main limitation of animal models are the interspecies differences between animal and human cells. At the contrary, in vitro model display the advantage to be set up with human cells. However, cellular models are often too simple, with cell growing in 2 dimensions on a plastic surface, very far to the organ structure in which cells are organized in 3 dimensions in the extracellular matrix.
Actually, the 3D cell organization impact on cell-cell communication, and thus impact cell response. Moreover, the ECM is involved not only in physical structure, but also in tissue homeostasis, biochemical signal retention and mediation, and thus in drug distribution. It is also involved in cell migration, differentiation and maturation (Clause and Barker, 2013; Sainio and Järveläinen, 2020; Su et al., 2017). More and more studies highlight the ECM modification and implication in neurodegenerative diseases (Bonneh‐Barkay and Wiley, 2009).
That is for all these reasons that it is necessary to take into account the 3D cell organization and the ECM in in vitro models, to enhance their relevance and their predictivity. In this aim HCS Pharma developed BIOMIMESYS®, a hyaluronic acid-based hydroscaffold which mimic the ECM and allows to cultivate cells in 3D.