Tissue Created with Biocompatible Embedded Nanoscale Wires

Lieber, a professor of chemistry at Harvard University (Cambridge, MA, USA) and Daniel Kohane, a Harvard Medical School professor in the department of anesthesia at Children’s Hospital Boston (MA, USA) developed a system for creating nanoscale “scaffolds,” which could be seeded with cells which later grew into tissue.

“The current methods we have for monitoring or interacting with living systems are limited,” said Prof. 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.”

The research tackles a problem that has long been associated with research on bioengineered tissue--how to create systems capable of sensing chemical or electrical alterations in the tissue after it has been grown and implanted. The system might also represent a solution to researchers’ struggles in developing 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,” Prof. 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.”

Using the autonomic nervous system as inspiration, Dr. Bozhi Tian, a former doctoral student under Prof. Lieber and former postdoctoral fellow in the Kohane and Langer labs, and collaborator Dr. Jia Liu worked in Prof. Lieber’s lab at Harvard to construct mesh-like networks of nanoscale silicon wires--approximately 30-80 nm in diameter--shaped like flat planes or in a reticular conformation. The process of building the networks, according to Prof. Lieber, is similar to that used to etch microchips.

Beginning with a two-dimensional (2D) substrate, researchers laid out a mesh of organic polymer around nanoscale wires, which serve as the critical nanoscale sensing elements. Nanoscale electrodes, which connect the nanowire elements, were then built within the mesh to enable nanowire transistors to measure the activity in cells without damaging them. Once complete, the substrate was dissolved, leaving researchers with a net-like sponge or a mesh that can be folded or rolled into a host of 3D shapes.

When finished, the networks were porous enough to allow the scientists to seed them with cells and induce those cells to grow in 3D cultures. “Previous efforts to create bioengineered sensing networks have focused on two-dimensional layouts, where culture cells grow on top of electronic components or on conformal layouts where probes are placed on tissue surfaces,” said Dr. 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."

Using heart and nerve cells, the team successfully engineered tissues containing embedded nanoscale networks without affecting the cells’ viability or activity. Using the embedded devices, they were able to detect electrical signals generated by cells deep within the tissue, and to measure changes in those signals in response to cardio- or neuro-stimulating drugs.

Researchers were also able to construct bioengineered blood vessels, and used the embedded technology to measure pH changes--as would be seen in response to ischemia, inflammation, and other biochemical or cellular environments--both inside and outside the vessels.

Although a number of potential applications exist for the technology, the most near-term use, according to Dr. Lieber, may come from the pharmaceutical industry, where researchers could employ the technology to more precisely examine how newly-developed drugs act in three dimensional tissues, instead of thin layers of cultured cells. The system might also one day be used to track changes inside the body and react accordingly, whether through electrical stimulation or the release of a drug.

Related Links:
Harvard University
Children’s Hospital Boston