Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

In vitro innovation: Testing nanomedicine with blood cells on a microchip

05.02.2014
Designing nanomedicine to combat diseases is a hot area of scientific research, primarily for treating cancer, but very little is known in the context of atherosclerotic disease.

Scientists have engineered a microchip coated with blood vessel cells to learn more about the conditions under which nanoparticles accumulate in the plaque-filled arteries of patients with atherosclerosis, the underlying cause of myocardial infarction and stroke.


This is a schematic of an endothelialized microfluidic device that consists of two-layer microfluidic channels that are separated by a porous membrane (3 ìm pore) on which endothelial cells are grown.

Credit: Credit: Kim/PNAS.

In the research, microchips were coated with a thin layer of endothelial cells, which make up the interior surface of blood vessels. In healthy blood vessels, endothelial cells act as a barrier to keep foreign objects out of the bloodstream. But at sites prone to atherosclerosis, the endothelial barrier breaks down, allowing things to move in and out of arteries that shouldn't.

In a new study, nanoparticles were able to cross the endothelial cell layer on the microchip under conditions that mimic the permeable layer in atherosclerosis. The results on the microfluidic device correlated well with nanoparticle accumulation in the arteries of an animal model with atherosclerosis, demonstrating the device's capability to help screen nanoparticles and optimize their design.

"It's a simple model — a microchip, not cell culture dish — which means that a simple endothelialized microchip with microelectrodes can show some yet important prediction of what's happening in a large animal model," said YongTae (Tony) Kim, an assistant professor in bioengineering in the George W. Woodruff School of Mechanical Engineering at the Georgia Institute of Technology.

The research was published in January online in the journal Proceedings of the National Academy of Sciences. This work represents a multidisciplinary effort of researchers that are collaborating within the Program of Excellence in Nanotechnology funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health (NIH). The team includes researchers at the David H. Koch Institute for Integrative Cancer Research at MIT, the Icahn School of Medicine at Mount Sinai, the Academic Medical Center in Amsterdam, Kyushu Institute of Technology in Japan, and the Boston University School of Medicine and Harvard Medical School.

Kim began the work as his post-doctoral fellow at the Massachusetts Institute of Technology (MIT) in the lab of Robert Langer.

"This is a wonderful example of developing a novel nanotechnology approach to address an important medical problem," said Robert Langer, the David H. Koch Institute Professor at Massachusetts Institute of Technology, who is renowned for his work in tissue engineering and drug delivery.

Kim and Langer teamed up with researchers from Icahn School of Medicine at Mount Sinai in New York. Mark Lobatto, co-lead author works in the laboratories of Willem Mulder, an expert in cardiovascular nanomedicine and Zahi Fayad, the director of Mount Sinai's Translational and Molecular Imaging Institute.

"The work represents a unique integration of microfluidic technology, cardiovascular nanomedicine, vascular biology and in vivo imaging. We now better understand how nanoparticle targeting in atherosclerosis works." Lobatto says.

The researchers hope that their microchip can accelerate the nanomedicine development process by better predicting therapeutic nanoparticles' performance in larger animal models, such as rabbits. Such a complimentary in vitro model would save time and money and require fewer animals.

Few nanoparticle-based drug delivery systems, compared to proposed studies, have been approved by the U.S. Food and Drug Administration, Kim said. The entire process developing one nanomedicine platform can take 15 years to go from idea to synthesis to testing in vitro to testing in vivo to approval.

"That's a frustrating process," Kim said. "Often what works in cell culture dishes doesn't work in animal models."

To help speed up nanomedicine research by improving the predictive capabilities of in vitro testing, Kim and colleagues designed their microchip to mimic what's going on in the body better than what is currently possible through routine cell culture.

"In the future, we can make microchips that are much more similar to what's going on in animal models, or even human beings, compared to the conventional cell culture dish studies," Kim said.

On their microchip, scientists can control the permeability of the endothelial cell layer by altering the rate of blood flow across the cells or by introducing a chemical that is released by the body during inflammation. The researchers discovered that the permeability of the cells on the microchip correlated well with the permeability of microvessels in a large animal model of atherosclerosis.

The microchips allows for precise control of the mechanical and chemical environment around the living cells. By using the microchip, the researchers can create physiologically relevant conditions to cells by altering the rate of blood flow across the cells or by introducing a chemical that is released by the body during inflammation.

Kim said that while this microchip-based system offers better predictability than current cell culture experiments, it won't replace the need for the animal studies, which provide a relatively more complete picture of how well a particular nanomedicine might work in humans.

"This is better than an in vitro dish experiment, but it's not going to perfectly replicate what's going on inside the body in near future," Kim said. "It will help make this whole process faster and save a number of animals."

This research is supported by the National Heart, Lung, and Blood Institute as a Program of Excellence in Nanotechnology Award (HHSN268201000045C), the National Cancer Institute (NCI) (CA151884); the David H. Koch Prostate Cancer Foundation Award in Nanotherapeutics, and the National Institutes of Health (NIH) (R01 EB009638 and R01CA155432). Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.

CITATION: YongTae Kim, et al., "Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis," (PNAS, January 2014). (http://dx.doi.org/10.1073/pnas.1322725111).

Brett Israel | EurekAlert!
Further information:
http://www.gatech.edu

More articles from Medical Engineering:

nachricht New investigation of endovenous laser ablation of varicose veins
11.05.2016 | Kazan Federal University

nachricht A laser for your eyes
18.04.2016 | Lomonosov Moscow State University

All articles from Medical Engineering >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

Im Focus: Transparent - Flexible - Printable: Key technologies for tomorrow’s displays

The trend-forward world of display technology relies on innovative materials and novel approaches to steadily advance the visual experience, for example through higher pixel densities, better contrast, larger formats or user-friendler design. Fraunhofer ISC’s newly developed materials for optics and electronics now broaden the application potential of next generation displays. Learn about lower cost-effective wet-chemical printing procedures and the new materials at the Fraunhofer ISC booth # 1021 in North Hall D during the SID International Symposium on Information Display held from 22 to 27 May 2016 at San Francisco’s Moscone Center.

Economical processing

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

LZH shows the potential of the laser for industrial manufacturing at the LASYS 2016

25.05.2016 | Trade Fair News

Great apes communicate cooperatively

25.05.2016 | Life Sciences

Thermo-Optical Measuring method (TOM) could save several million tons of CO2 in coal-fired plants

25.05.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>