writes copy 22 Dec 2017

3D Printed Biomimetic Blood Brain Barrier Eliminates Need for Animal Testing

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Scanning electron microscopy image of the bio-hybrid BBB model. [Image: Gianni Ciofani, IIT]

The blood-brain barrier (BBB) may sound like a rating system for avoiding horror movies, but in reality it is a semi-permeable membrane responsible for restricting and regulating the entry of neurotoxic compounds, diseases, and circulating blood into the brain. It exists as a defense mechanism to protect the brain from direct contact with damaging entities carried in the body. Normally, this is something that is important to maintain as a strong defense; however, there are times when medical treatments require the ability to trespass beyond this biological barrier without damaging it. This is especially true now in the era of nanomedicine, when therapeutic treatments have been developed to combat brain cancer, neurogenerative diseases, and even the effects of trauma-based brain damage.

In order to advance medical research in these important areas, it has been important to operate in an environment that accurately represents the BBB. As such, researchers have turned to animal subjects, something which comes with significant ethical and moral questions. The desire has been, therefore, to create some type of substitute for a living creature, but limits to current fabrication techniques had made such models impossible to produce. That is, until now. In an article recently published in the journal  Small researchers detailed a breakthrough in high resolution 3D printing that has allowed them to “faithfully reproduc[e] the microcapillaries of the neurovascular system on a 1:1 scale.” As explained by Gianni Ciofani, Associate Professor at Polytechnic University of Torino and Principal Investigator of the Smart Bio-Interfaces group at the Italian Institute of Technology:

“The bio-hybrid BBB developed in our laboratories allows [one] 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 [one] 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.”

Confocal acquisition of the bio-hybrid BBB model (f-actin, ZO-1 and nuclei of bEnd3 cells have been stained in red, green and blue respectively). [Image: Gianni Ciofani, IIT]

This mimicked BBB is important for developing methods by which pharmaceuticals can cross the boundary as there currently exist drug compounds that demonstrate great potential for addressing brain diseases, but that are currently unable to penetrate the barrier. The models created consist of porous microtubes that provide the scaffolding upon which endothelial cells can be grown in order to create a replica of the barrier present in the membrane. This will allow medical researchers to undertake their investigations in real time in an environment that accurately presents the circumstances under which the intervention would take place in the real world. As Ciofani described:

“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. 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 turned and monitored, thus providing precious and detailed information about the BBB crossing in real time and at cellular/subcellular levels.”

3D rendering of confocal acquisition of the bio-hybrid BBB model (f-actin, ZO-1 and nuclei of bEnd3 cells have been stained in red, green and blue respectively). [Image: Gianni Ciofani, IIT]

This is an important advance in the study of ways in which medicine can address diseases such as Alzheimer’s, Parkinson’s, and ALS as well as an important part of advancing treatments for those suffering from trauma induced brain damage.  Ciofani concluded:

“We strongly believe that nanotechnology-based solutions such as nanocarriers and nanovectors for thernostic applications show enormous potential for the treatment of brain pathologies…In this context, the new generation of remotely triggered smart nanomaterials represents, in our opinion, the future solution for the treatment of brain diseases. The BBB model we developed represents a powerful testing tool to achieve these goals.”

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[Source: Nanowerk]

 

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