Summary

With over 700,000 affected patients in the EU, Multiple Sclerosis (MS) represents the most frequently occurring demyelinating disease of the central nervous system (CNS). Remyelination can be observed in MS plaques. But as the disease progresses this regenerative capacity ofoligodendrocyte progenitor cells (OPCs) stops. What are the reasons underneath this change? One accepted reason is the formation of the scar tissue, which is seen as a hostile terrain in the context of CNS regeneration. Although the process is inexorable, it is mutable in time. Can we use this knowledge as an opportunity to manage the disease progression?

There is growing evidence that matrix rigidity plays a key role in the process of OPC differentiation and oligodendrocyte myelination by unbalancing the intra/extracellular forces. Recent studies have established the effect of biophysical properties of the extracellular matrix (ECM) on these processes, pointing to the importance of ECM stiffness and topography, strain forces and spatial constraints. Based on current knowledge, our working hypothesis is that by tuning mechanosensing processes one can promote remyelination.

This innovative approach aimed to develop a biomimetic lesion microenvironment to function as a platform to allow the identification of molecules/mechanisms regulating OPC differentiation and study the impact of the mechanical properties on MS progress and prognosis, thus ultimately contributing to the development of new therapeutic approaches to treat MS.

The proposed tissue-engineered system should mimic the ECM features at the relapse and remitting stages of the disease, where a therapeutic intervention at the OPC level could promote a pro-regenerative response. Furthermore, the team aimed to miniaturize and automatize the screening process, by developing a custom-made bioprinter, to allow performing these studies on a high-throughput basis, thus reducing costs and increasing the power of analysis.

The proposed tunable TE-scar represents a revolutionizing attractive system that can be explored in the context of other neurological disorders or even neurodevelopmental studies. Furthermore, the bioprinter prototype can find application in many other uses in biomedicine.