Dec 22, 2017 | By David

The combination of 3D printing with microfluidics technology is a field of research that continues to go from strength to strength, with all kinds of pioneering work offering the potential for medical treatments and other crucial applications. The latest breakthrough has been achieved by a team of researchers in Italy, who have succeeded in replicating the blood-brain barrier to an unprecedented level of accuracy. Their 3D printed bio-hybrid microfluidics model faithfully reproduces the microcapillaries of the neurovascular system, on a 1:1 scale, for the first time ever.

The research project was detailed in a paper entitled "A 3D Real-Scale, Biomimetic, and Biohybrid Model of the Blood-Brain Barrier Fabricated through Two-Photon Lithography", published in the journal Small.

The pharmaceutical treatment of brain diseases and neurodegenerative conditions, such as Alzheimer’s or Parkinson ’s disease, is something that many public and private institutions are pouring a lot of resources into. It is a challenge for lots of reasons, particularly due to the inaccessibility of the central nervous system for testing. This is why highly accurate models such as microfluidics ones are very important, as a way to work around this. One of the main problems currently faced by research in this field is that it is difficult to identify exactly which bio-chemical mechanisms are involved in the crossing of certain substances and molecules over the blood-brain barrier.

According to Gianni Ciofani, an Associate Professor at Polytechnic University of Torino and the Principal Investigator of the Smart Bio-Interfaces group at the Italian Institute of Technology, ''The bio-hybrid BBB developed in our laboratories allows to carry out high-throughput screening of different drugs/compounds/nanovectors, and to evaluate their ability to cross the BBB...Furthermore, our bio-hybrid platform allows to rigorously study the BBB crossing by avoiding the use of animal models, thus overcoming the issues related to the scarce accessibility of the brain and limiting important ethical concerns."

The system is referred to as bio-hybrid due to the combination of artificial and biological elements in the model. The capillaries are made up of micro-tubes, 3D printed using the two-photon lithography technique, and endothelial cells which are grown around the scaffold of this artificial tubular structure. This organic barrier functions very similarly to the BBB, which separates the inside of the blood vessels from the brain itself.

The BBB is important as it protects the brain from neurotoxic compounds, pathogens, and circulating blood cells. In order for nanomedicine applications to deliver a therapeutical compound from the blood system into the brain, this selective biological barrier has to be overcome. Recreating the BBB and mimicking the in vivo environment as closely as possible is therefore crucial in the development of new therapies against brain cancer and for the treatment of neurodegenerative diseases.

"The novelty of our work mainly consists in the fabrication of a reliable platform to carry out high-throughput quantitative investigations of drug delivery to the brain," Ciofani says. "The in vitro model provides a closed system where the different variables such as drug concentration, blood flow speed, pH, and temperature can be easily tuned and monitored, thus providing precious and detailed information about the BBB crossing in real time and at cellular/subcellular level."

The end goal of the team’s research is to modify anti-cancer nanovectors in such a way that they can cross the BBB through the blood system and target diseased tissues in the brain. Their next step will be to test a variety of different drugs/smart nanoparticles/anticancer agents, hoping to improve their crossing of the BBB and their targeting of specific cells.

"We strongly believe that nanotechnology-based solutions such as nanocarriers and nanovectors for theranostic applications show enormous potential for the treatment of brain pathologies," Ciofani notes. "However, in order to achieve a realistic implementation of nanomaterials into the clinical practice, it is extremely important to address safety issues. Since most nanomaterials also accumulate in peripheral body regions – e.g., spleen, liver and kidney – it is of extreme importance that such nanovectors release the drugs/compounds only in the brain, and, specifically, in the region of the diseased tissue."



Posted in 3D Printing Application

Source: Nanowerk


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