Light-Activated Implants Signal Specific Deep Tissue

A number of novel therapies under development rely on inducing specific cells to do specific things, but getting the right message to the right group of cells — and at the right time — remains a major challenge. And the use of light to communicate with cells has been restricted by its difficulty in passing through tissue. Now, however, new light-activated implants have been developed that its creators say can deliver light signals to specific tissues deep within the body.

"Scientists only began investigating light-activated therapy a few years ago, but it is generating huge interest," said Seok Hyun "Andy" Yun, director of the Harvard University Bio-Optics Lab, an investigator at the Wellman Center for Photomedicine at Massachusetts General Hospital and senior author of a study on the work. "One of the best known example is use of optogenetics — activation or deactivation of brain cells by illumination with different colors of light — to treat brain disorders. But how to deliver light deep within the brain or other tissues has been a common problem. The implant we have developed may help solve this problem."

An artistic illustration of cells encapsulated in a hydrogel implanted in the body. Courtesy of Harvard Bio-Optics Lab.

Yun and Harvard colleague Malte C. Gather made headlines in 2011 when they reported the first successful biological laser based on a single living cell.

The new matchstick-sized, biocompatible and highly transparent polymer implants contain synthetic cells genetically modified to activate in response to light. Such implants could be important for a wide range of diagnostic and therapeutic applications, such as an optical treatment for diabetes or real-time monitoring of toxins in the body.

Called a light-guiding hydrogel, the implant, constructed from a polymer-based scaffolding capable of supporting living cells, contains cells genetically engineered either to carry out a specific activity in response to light or to emit light in response to a particular metabolic signal. An optical fiber connects the implant to either an external light source or a light detector.

The researchers, from Harvard, the Wellman Center and the Korea Advanced Institute of Science and Technology, demonstrated the medical utility of the implants by using them to regulate blood glucose levels in diabetic mice. Yun and colleagues used blue light supplied through an optical fiber to the implant to induce the cells in the implant to synthesize a protein that stimulates insulin production.

In another demonstration, the team created implants with cells that emit green light when stressed by the presence of certain toxins, such as heavy metals. By measuring light levels emitted by the implant, such implants could be used in the future as sensors for monitoring toxin levels in patients in real time.

"This work combines several existing technologies well-known in their respective fields - such as drug delivery, genetic engineering, biomaterial science, and photonics — to build a new implant system that enables the delivery of photomedicine deep in the body," Yun said. "This is the first time anyone has shown the ability to talk optically — by means of light — with cells deep within the body, both to sense the presence of a toxin and to deliver a cell-based therapy."

Schematic of a hydrogel encapsulating cells for sensing and therapy. The light-guiding hydrogel establishes bidirectional optical communications with the cells, allowing real-time interrogation and control of the biological system in vivo. Courtesy of Harvard Bio-Optics Lab.

The researchers add that future studies should investigate how changing the shape and structure of the hydrogel can improve the implant's light-guiding properties, ways to improve the production and delivery of a therapeutic protein, how the immune system would react to long-term implantation, and ways to deliver or detect the light signal that would not require passing a fiber through the skin.

The work is published online in Nature Photonics (doi: 10.1038/nphoton.2013.278); lead author of the article is Myunghwan Choi, Ph.D., of the Wellman Center. Additional co-authors are Jin Woo Choi, Sedat Nizamoglu and Sei Kwang Hahn, Ph.D., Wellman Center; and Seonghoon Kim, Korea Advanced Institute of Science and Technology.

Support for the study includes grants from the National Institutes of Health, National Science Foundation and US Department of Defense.

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