Silk biomaterials for brain-penetrating devices.

摘要

Recent research has positioned direct brain-interfacing technologies, such as the neuroprosthetic control of robotic limbs, at the cusp of clinical reality. However, a significant challenge remains in that current brain-penetrating electrode devices often lose the ability to record stable neuron populations over time. One factor thought to contribute to this lack of chronic reliability is the inflammatory response, known as gliosis, and resulting tissue encapsulation that occurs at the recording site. Device functionality may be improved by enhancing probe biocompatibility through reduction of gliosis around the implant. Silk possesses a unique combination of characteristics, including dynamic, hydration-mediated mechanical properties, and the capacity for delivering sensitive therapeutics, that make it an excellent candidate biomaterial for meeting the challenges specific to brain implants.;In this work, the utility of silk for constructing brain-penetrating devices is investigated across a broad spectrum ranging from basic material properties to biological responses. Various fabrication strategies are employed, which allow for the application of silk coatings to electrodes, as well as for the creation of high-resolution, arbitrarily-shaped silk structures. The buckling mechanics of silk shanks are shown to be sufficient to deliver electrode devices, which otherwise are too flexible, into brain tissue. A study into the real-time, dynamic swelling characteristics of silk films is carried out, providing mechanistic insight into this phenomenon, as well as practical considerations for devices which transition from a dry to hydrated state upon implantation. The response of brain cells to silk materials is assessed using an in vitro model of glial scarring around an implant, with silk coatings shown to elicit a reduced scarring response relative to microwire controls. In addition, silk is shown capable of encapsulating and releasing a sensitive enzyme which further reduces some of the inhibitory aspects of the glial scar. Finally, brain-penetrating silk devices are tested in an animal model, with preliminary results indicating favorable outcomes for silk and functionalized silk devices relative to microwire controls.