Implantable Silk Micromirrors Enhance Imaging

Silk-based implantable optics that significantly enhance tissue imaging can simultaneously enable photothermal therapy, monitor drug delivery and administer drugs.

The biodegradable and biocompatible tiny mirror-like devices, developed by Fiorenzo Omenetto of Tufts University, dissolve harmlessly at predetermined rates and require no surgery for removal. The technology stems from several years of research exploring ways to leverage the silk’s optical capabilities along with its capacity as a resilient, biofriendly material that can stabilize other materials while maintaining their biochemical functionality.

A microscopic image of a silk optical implant created when purified silk protein is poured into molds in the shape of multiple microsized reflectors and then air-dried. When implanted in tissue and illuminated, the “silk mirrors” caused more light to be reflected from within the tissue, enhancing imaging. Later, the reflector was harmlessly reabsorbed in living tissue and did not need to be removed. Courtesy of Fiorenzo Omenetto.

“This work showcases the potential of silk to bring together form and function,” Omenetto said. “In this case an implantable optical form — the mirror — can go beyond imaging to serve multiple biomedical functions.”

A purified silk protein solution was poured into molds of multiple microsized prism reflectors, or microprism arrays (MPAs), to create the optical devices. Regulating the water content of the solution during the process enabled the bioengineers to predetermine the rates at which the devices would dissolve in the body. The cast solution was then air-dried to form solid silk films in the form of the mold. The resulting silk sheets were similar to the reflective tape found on traffic signs or safety garments.

When implanted, these MPAs reflected back photons that ordinarily are lost with reflection-based imaging technologies, thereby enhancing the imaging even in deep tissue.

The devices were tested using solid and liquid phantoms — materials that mimic the scattering that occurs when light passes through human tissue. The MPA-formed silk films reflected substantially stronger optical signals in comparison to films that had not been formed as MPAs.

The researchers also demonstrated the silk mirrors’ potential for administering therapeutic treatments by mixing gold nanoparticles into the solution before casting the MPAs. The gold-silk mirror was implanted under the skin of mice and illuminated with green laser light, which converted the nanoparticles from light to heat. Similar in vitro experiments showed that the devices inhibit bacterial growth while maintaining optical performance.

Doxorubicin, a cancer-fighting drug, was also embedded in the MPAs. The team observed that the drug remained active even at high temperatures (60 °C), underscoring the ability of silk to stabilize chemical and biological dopants. When exposed to enzymes in vitro, the drug was released as the mirror gradually dissolved. The amount of reflected light decreased as the mirror degraded, allowing the researchers to accurately assess the drug delivery rate.

"The important implication here is that using a single biofriendly, resorbable device one could image a site of interest, such as a tumor, apply therapy as needed and then monitor the progress of the therapy,” Omenetto said.

The technology was described in the Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1209056109).

For more information, visit: www.tufts.edu

For more about the use of silk-based optics, see: Silk’s Photonic Talents Brought to Light at FiO 2012