Tag Archives: Hu Tao

Silk inks containing enzymes, antibiotics, antibodies, nanoparticles, and growth factors

There’s an almost euphoric tone to a June 16, 2015 Tufts University news release (also on EurekAlert) about research which has resulted in the ability to print silk-based inks,

Silk inks containing enzymes, antibiotics, antibodies, nanoparticles and growth factors could turn inkjet printing into a new, more effective tool for therapeutics, regenerative medicine and biosensing, according to new research led by Tufts University  biomedical engineers and published June 16 [2015] in the journal Advanced Materials online in advance of print.

Until now, heat used in the inkjet printing process made using silk a challenge (as it does for cellulose nanomaterials used in 3D printers, noted in my June 17, 2015 posting), from the Tufts news release,

Inkjet printing is one of the most immediate and accessible forms of printing technology currently available, according to the researchers, and ink-jet printing of biomolecules has been previously proposed by scientists. However, the heat-sensitive nature of these unstable compounds means printed materials rapidly lose functionality, limiting their use.

Enter purified silk protein, or fibroin, which offers intrinsic strength and protective properties that make it well-suited for a range of biomedical and optoelectronic applications. This natural polymer is an ideal “cocoon” that can stabilize compounds such as enzymes, antibodies and growth factors while lending itself to many different mechanically robust formats, said Fiorenzo Omenetto, Ph.D., senior author on the paper and associate dean for research and Frank C. Doble Professor of Engineering at Tufts School of Engineering.

“We thought that if we were able to develop an inkjet-printable silk solution, we would have a universal building block to generate multiple functional printed formats that could lead to a wide variety of applications in which inks remain active over time,” he said.

By using this simple approach and starting with the same base material, the research team created and tested a “custom library” of inkjet-printable, functional silk inks doped with a variety of components:

  • Bacterial-sensing polydiacetylenes (PDAs) printed on surgical gloves; the word “contaminated” printed on the glove changed from blue to red after exposure to E. coli
  • Proteins that stimulate bone growth (BMP-2) printed on a plastic dish to test topographical control of directed tissue growth
  • Sodium ampicillin printed on a bacterial culture to test the effectiveness of a topographical distribution of the antibiotic
  • Gold nanoparticles printed on paper, for possible application in photonics and biology (e.g., color engineering, surface plasmon resonance based sensing and bio-imaging)
  • Enzymes printed on paper to test the ability of the ink to entrain small functional biomolecules

The researchers, who included collaborators from the University of Illinois at Urbana-Champaign, foresee wide potential for future investigation and application of this technology.

For example, Omenetto envisions more work on the bio-sensing gloves, which he says could selectively react to different pathological agents. The ability to print antibiotics in topographical patterns could address the need for “smart” bandages, where therapeutics are incorporated and delivered to match a complex injury.

The published research was restricted to one ink cartridge, but the scientists believe it could extend to multi-cartridge printing combining complex functions.

Omenetto and Kaplan are pioneers in the use of silk as an alternative to plastics. Omenetto’s 2011 TED Talk called silk a “new old material” that could have a profound impact in many technical fields.

Here’s a link to and citation for the paper,

Inkjet Printing of Regenerated Silk Fibroin: From Printable Forms to Printable Functions by Hu Tao, Benedetto marelli, Miaomiao Yang, Bo An, Serdar Onses, John A. Rogers, David L. Kaplan, & Fiorenzo G. Omenetto. Advanced Materials DOI: 10.1002/adma.201501425 First published: 16 June 2015

This article is behind a paywall.

Tooth tattoos at Tufts University

In spring 2012, there was a fluttering in the blogosphere about tooth tattoos with the potential for monitoring dental health. As sometimes happens, I put off posting about the work until it seemed everyone else had written about it (e.g. Mar. 30, 2012 posting by Dexter Johnson for his Nanoclast blog on the IEEE website) and there was nothing left for me to say.  Happily, the researchers at Tufts University (where part of this research [Princeton University is also involved] is being pursued) have released more information in a Nov. 1, 2012 news article by David Levin,

The sensor, dubbed a “tooth tattoo,” was developed by the Princeton nanoscientist Michael McAlpine and Tufts bioengineers Fiorenzo Omenetto, David Kaplan and Hu Tao. The team first published their research last spring in the journal Nature Communications.

The sensor is relatively simple in its construction, says McAlpine. It’s made up of just three layers: a sheet of thin gold foil electrodes, an atom-thick layer of graphite known as graphene and a layer of specially engineered peptides, chemical structures that “sense” bacteria by binding to parts of their cell membranes.

“We created a new type of peptide that can serve as an intermediary between bacteria and the sensor,” says McAlpine. “At one end is a molecule that can bond with the graphene, and at the other is a molecule that bonds with bacteria,” allowing the sensor to register the presence of bacteria, he says.

Because the layers of the device are so thin and fragile, they need to be mounted atop a tough but flexible backing in order to transfer them to a tooth. The ideal foundation, McAlpine says, turns out to be silk—a substance with which Kaplan and Omenetto have been working for years.

By manipulating the proteins that make up a single strand of silk, it’s possible to create silk structures in just about any shape, says Omenetto, a professor of biomedical engineering at Tufts. Since 2005, he’s created dozens of different structures out of silk, from optical lenses to orthopedic implants. Silk is “kind of like plastic, in that we can make [it] do almost anything,” he says. “We have a lot of control over the material. It can be rigid. It can be flexible. We can make it dissolve in water, stay solid, become a gel—whatever we need.”

Omenetto, Kaplan and Tao created a thin, water-soluble silk backing for McAlpine’s bacterial sensor—a film that’s strong enough to hold the sensor components in place, but soft and pliable enough to wrap easily around the irregular contours of a tooth.

To apply the sensor, McAlpine says, you need only to wet the surface of the entire assembly—silk, sensor and all—and then press it onto the tooth. Once there, the silk backing will dissolve within 15 or 20 minutes, leaving behind the sensor, a rectangle of interwoven gold and black electrodes about half the size of a postage stamp and about as thick as a sheet of paper. The advantage of being attached directly to a tooth means that the sensor is in direct contact with bacteria in the mouth—an ideal way to monitor oral health.

Because the sensor doesn’t carry any onboard batteries, it must be both read and powered simultaneously through a built-in antenna. Using a custom-made handheld device about the size of a TV remote, McAlpine’s team can “ping” that antenna with radio waves, causing it to resonate electronically and send back information that the device then uses to determine if bacteria are present.

The sensor (A), attached to a tooth (B) and activated by radio signals (C), binds with certain bacteria (D). Illustration: Manu Mannoor/Nature Communications (downloaded from http://now.tufts.edu/articles/tooth-tattoo)

In addition to its potential for  monitoring dental health, the tooth tattoo could replace some of the more invasive health monitoring techniques (e.g., drawing blood), from the Tufts University article,

In addition to monitoring oral health, Kugel [Gerard Kugel, Tufts professor of prosthodontics and operative dentistry and associate dean for research at Tufts School of Dental Medicine] believes the tooth tattoo might be useful for monitoring a patient’s overall health. Biological markers for many diseases—from stomach ulcers to AIDS—appear in human saliva, he says. So if a sensor could be modified to react to those markers, it potentially could help dentists identify problems early on and refer patients to a physician before a condition becomes serious.

“The mouth is a window to the rest of the body,” Kugel says. “You can spot a lot of potential health problems through saliva, and it’s a much less invasive way to do diagnostic tests than drawing blood.”

Before monitoring of any type can take place, there is at least one major hurdle still be overcome. Humans are quite sensitive to objects being placed in their mouths. According to one of the researchers, we can sense objects that are 50 to 60 microns wide, about the thickness piece of paper, and that may be too uncomfortable to bear.

H/T Nov. 9, 2012 news item on Nanowerk for pointing me towards the latest information about these tooth tattoos.