Brain-on-a-chip as a preclinical model tool
Dementia, a term that includes a myriad of disorders that result in a decline in brain function, affects around 10 million people in Europe alone – a number that is expected to double by the end of the decade. Yet despite decades of research, effectively treating these diseases remains elusive. “The brain’s complexity makes it tremendously challenging to predict and find new medical solutions,” says Manuel Bañobre, a researcher at the International Iberian Nanotechnology Laboratory(opens in new window). As a result, 2D cell culture and animal models have become the gold standard for drug development and research. However, in addition to ethical concerns, these models cannot perfectly mimic the brain’s physiological settings and complexity. Filling this technological gap are brain-on-a-chip (BoC) devices. “By decoupling the brain into various cellular structures while maintaining their interconnections, BoC devices offer a promising, user-friendly tool for conducting preclinical models,” adds Bañobre. Helping leverage this promise is the EU-funded BrainChip4MED project.
Modelling the blood-brain barrier
The project, which received support from the Marie Skłodowska-Curie Actions(opens in new window) (MSCA) programme, focused on modelling the blood-brain barrier (BBB). “The BBB has evolved as an extra protection system of blood vessels, working as a gatekeeper that prevents toxins and other harmful substances from reaching the brain,” explains Raquel Rodrigues, the MSCA researcher on the project. As Bañobre remarks, the BBB’s efficacy is based on the physiological conformation of the vascular endothelial cells. This forms tight and adhesive junctions, creating a semi-permeable barrier with no fenestration and that restricts the free diffusion and rapid exchange of molecules between the blood and the brain. “This protective BBB is also one of the main challenges to creating effective drugs that can cross this blood barrier and target brain cells,” remarks Bañobre, who serves as the project’s coordinator.
Advancing the state of the art in blood-brain barrier models
To overcome this challenge, researchers developed an innovative bio-membrane based on the native extracellular matrix of the brain. Built using a new pro-angiogenic gelatine-based membrane that can load and release the growth factors needed to promote neuronal vascularisation, the bio-membrane closely mimics the brain’s mechanical properties, hydration and adhesion cues. The result of this work is a simple, rapid and non-toxic method for producing an accurate BBB bio-membrane capable of sustaining and generating ideal conditions for the spread, adhesion and tight junction formation of vascular endothelial cells for several days. “This represents a significant advance in the current state of the art for developing BBB models,” notes Bañobre.
A big step towards better healthcare for all
Ultimately, the project succeeded in designing a nanomedical platform that enables the screening of relevant formulations for therapeutic delivery to the brain. It also developed a novel optical biosensing strategy to monitor Alzheimer’s disease hallmarks during preclinical trials. “This is an important first step towards delivering a preclinical tool with the potential to guide prognosis and support more effective therapeutic decisions for medicines or other nanotherapeutic systems designed for neurodegenerative diseases, ensuring better healthcare and well-being for all,” concludes Rodrigues. Rodrigues continues to work on developing the BrainChip4MED prototype, with a specific focus on integrating biosensing systems for the real-time, continuous screening of drugs and drug nanocarriers being developed for neurodegenerative diseases.
