Growing Artificial Tissues with Embedded Nanoscale Sensors
Author: Boston Children's Hospital
- Method for embedding networks of biocompatible nanoscale wires within engineered tissues allowing direct tissue sensing and potentially stimulation.
Main DigestResearchers develop method to grow artificial tissues with embedded nanoscale sensors - "Cyborg" tissues could merge bioengineering with electronics for drug development, implantable therapeutics.
Nanotechnology - A basic definition: Nanotechnology is the engineering of functional systems at the molecular scale. A nanometer (nm) is one-billionth of a meter, smaller than the wavelength of visible light and a hundred-thousandth the width of a human hair. In general, nanotechnology dealing with anything measuring between 1 and 100 nm. Larger than that is the micro-scale, and smaller than that is the atomic scale.
A multi-institutional research team has developed a method for embedding networks of biocompatible nanoscale wires within engineered tissues. These networks - which mark the first time that electronics and tissue have been truly merged in 3D - allow direct tissue sensing and potentially stimulation, a potential boon for development of engineered tissues that incorporate capabilities for monitoring and stimulation, and of devices for screening new drugs.
The researcher team - led by Daniel Kohane, MD, PhD, in the Department of Anesthesia at Boston Children's Hospital; Charles M. Lieber, PhD, at Harvard University; and Robert Langer, ScD, at the Massachusetts Institute of Technology - reported their work online on August 26 in Nature Materials.
One of the major challenges in developing bio-engineered tissues is creating systems to sense what is going on (e.g., chemically, electrically) within a tissue after it has been grown and/or implanted. Similarly, researchers have struggled to develop methods to directly stimulate engineered tissues and measure cellular reactions.
"In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed," Kohane explained. "We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level."
With the autonomic nervous system as inspiration, a postdoctoral fellow in the Kohane lab, Bozhi Tian, PhD, and his collaborators built mesh-like networks of nanoscale silicon wires - about 80 nm in diameter - shaped like flat planes or in a "cotton-candy"-like reticular conformation. The networks were porous enough to allow the team to seed them with cells and encourage those cells to grow in 3D cultures.
"Previous efforts to create bio-engineered sensing networks have focused on 2D layouts, where culture cells grow on top of electronic components, or on conformal layouts where probes are placed on tissue surfaces," said Tian. "It is desirable to have an accurate picture of cellular behavior within the 3D structure of a tissue, and it is also important to have nanoscale probes to avoid disruption of either cellular or tissue architecture."
"The current methods we have for monitoring or interacting with living systems are limited," said Lieber. "We can use electrodes to measure activity in cells or tissue, but that damages them. With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin."
"Thus far, this is the closest we've come to incorporating into engineered tissues electronic components near the size of structures of the extracellular matrix that surrounds cells within tissues," Kohane added.
Using heart and nerve cells as their source material and a selection of biocompatible coatings, the team successfully engineered tissues containing embedded nanoscale networks without affecting the cells' viability or activity. Via the networks, the researchers could detect electrical signals generated by cells deep within the engineered tissues, as well as measure changes in those signals in response to cardio- or neuro-stimulating drugs.
Lastly, the team demonstrated that they could construct bio-engineered blood vessels with embedded networks and use those networks to measure pH changes within and outside the vessels - as would be seen in response to inflammation, ischemia and other biochemical or cellular environments.
"This technology could turn some basic principles of bioengineering on their head," Kohane said. "Most of the time, for instance, your goal is to create scaffolds on which to grow tissues and then have those scaffolds degrade and dissolve away. Here, the scaffold stays, and actually plays an active role."
The team members see multiple future applications for this technology, from hybrid bio-engineered "cyborg" tissues that sense changes within the body and trigger responses (e.g., drug release, electrical stimulation) from other implanted therapeutic or diagnostic devices, to development of "lab-on-a-chip" systems that would use engineered tissues for screening of drug libraries.
The study was supported by the National Institutes of Health (NIH Director's Pioneer Award, grant numbers DE0113023, DE016516, GM073626), the McKnight Foundation and Boston Children's Hospital.
Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and nine members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 395 bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children's, visit: vectorblog.org
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