ERC Advanced Grant 2025 “ANDROMEDA: A bioengiNeered platform to address the DRivers of micrO/nanoplastic accuMulation in hEalthy and DiseAsed brains” Id 101264443

Brain exposure to micro- and nanoplastics (MNPs) has become a great concern: MNPs have been found in the human brain, with an exponential increase of their median concentration in the last eight years and higher values found in diseased brains. MNPs accumulation impairs brain functionality, affecting the permeability of the blood-brain barrier, which protects our functional brain tissue, namely the brain parenchyma, from harmful molecules penetration. The biochemical mechanisms involved are still unknown: there is an urgent need to reveal the key MNPs drivers affecting MNPs-brain interaction, to reduce MPNs accumulation and brain damage incidence. ANDROMEDA project poses the hypothesis that MNPs accumulation is due to specific MNPs chemical and geometrical features which impair the glymphatic system, an anatomical structure that generates a fluid flux to wash away undesired molecules from the brain parenchyma. Current in vivo and in vitro models are inadequate to address my hypothesis: in my vision, a model representing the glymphatic system mass transport and its cross-talk with the blood-brain barrier and the brain parenchyma is mandatory to fulfil this gap. To validate ANDROMEDA hypothesis, we will develop a revolutionary microphysiological system, to represent the brain vascular and glymphatic system circulation biomechanics at the microscale. ANDROMEDA platform will allow delivering a diagram indicating the “green zone” where the combinations of selected MNPs features cause the lowest glymphatic system impairment and impact on the blood-brain barrier permeability and brain parenchyma functionality. ANDROMEDA project is ground-breaking in its innovative bioengineering-based approach, addressing MNPs accumulation by using a microfabricated model of brain vascularisation. It will open a new perspective to address MNPs impact on brain with a huge impact on bioengineering, microphysiological systems, microfabrication, polymer science, boosting also our knowledge on brain disease in neuroscience.