BrainChip4MED · Brain-on-a-chip as a preclinical model tool for the screening of theranostic nanoformulations for neurodegenerative diseases

Brain-on-a-chip as a preclinical model tool for the screening of theranostic nanoformulations for neurodegenerative diseases

Dementia, which includes a broad category of brain disorders that decline brain function, has for a long time been a global challenge that was dismissed by pharmaceutical companies due to the low penetration efficiency of drugs that are able to cross the blood-brain barrier (BBB), as well as to the limited understanding of the underlying biophysical mechanism, which is still mostly unknown. Recently, brain-on-a-chip (BoC) has emerged as an advanced microfluidic platform combined with 3D tissue culture techniques, with the potential to create an accurate and simple-to-use preclinical model tool, by decoupling a complex organ, such as the brain, into different cellular structures, while maintaining their interconnections. Also, the possibility of integrating biosensors on it could extend its monitoring and workability for longer periods of time. Motivated by the lack of an appropriate in-vitro model to study brain-targeting drug nanocarriers, and the potentiality of BoC technology to recapitulate human biology and predict in-vivo response, the overreaching aim of this action is to develop an advanced microfluidic preclinical device with the structural and functional aspects of the brain tissue and BBB, using BoC as a preclinical model tool to assess and study possible alternatives for the diagnosis and treatment (i.e., theranostic) of neurodegenerative disorders, and to develop multifunctional novel stimuli-responsive drug nanocarrier systems (Figure 1). By so, BrainChip4MED prototype (mimicking the neural tissue and BBB integrated with multiplexed biosensors) proposed in this engineered platform is a cutting-edge technology that allows for the study of new drug delivery strategies and treatments of neurological diseases, such as Alzheimer’s disease (AD). Overall, the most innovative achievements during this action were (1) the development and optimisation of a novel pro-angiogenic hydrogel for (bio)engineering of the BBB and, (2) the development of a novel strategy of optical biosensing of AD hallmarks (i.e., amyloid beta) for the continuous and automatised monitoring of the AD models during preclinical trials. These scientific and technological achievements create an innovation in the current state-of-the-art for BoC as preclinical tools. The presented technology, represent a first step to achieve automatised BoCs with high potential to impact the society by delivering an advanced microfluidic device capable to reduce the use of animal tests, increase the successful rates in the translation of novel nanoformulations from laboratory to clinical use, and find a successful strategy that allows a better understanding and treatment of AD and dementia.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз