Fully Injectable Tissue Engineered Bioelectronics for the Brain

Stable, long-term integration between implanted devices and the brain remains a challenge. Properly interfaced neural implants provide the potential for recording brain activity, enabling the generation of neurally-driven prosthetics, treatment of neuroses, and a deeper understanding of brain function, among other applications. One of the major issues inhibiting long-term recordings of the brain is the lack of integration between an implant and surrounding tissue. This lack of integration often results in an inflammatory and subsequent scarring response driven by mechanical mismatches between the probe and adjacent tissue, as well as damage caused during implant placement. Tissue engineered implants provide a solution to this problem through their superior integrative capacity <i>in vivo </i>but traditionally lack any interactive components. To generate a tissue engineered neural probe, we have combined the recording capabilities of bioelectronic devices with the regenerative capacity of cellularized, tissue engineered implants to create a new implant system. Here, we developed a fully injectable bioelectronic, tissue engineered implant system for integration with the brain.<br/><br/>We constructed a bioelectronic device with a minimized cross-section and individually articulable leads (32 leads, each 8 x 4 μm in cross-section) to reduce the footprint of the device at the implantation site. We utilized a needle to place the device and to inject a tissue engineered matrix containing primary neurons to assist in implant placement and integration between the device and surrounding tissue. After 3 weeks, the tissue engineered insertion site was well-integrated into surrounding tissue with no clear boundary between the insertion site and brain. The interior of the implant site is entirely cellularized, primarily with neurons. A minimal microgial response was noted at the insertion site. Astrocytes were visible within the boundaries of the implant site as well. Astrocytes were also surrounding the implant site but not in conjunction with microglia, likely indicating remodeling of the insertion site. Conversely, in the control, a large boundary, consisting of astrocytes and microglia, is visible, and the interior of the implant site contained fragmented tissue.<br/><br/>We show the design and implementation of a fully injectable system for placing tissue engineered bioelectronic implants into the brain. This system allows for the placement of viable cell populations along with functional bioelectronic recording devices that integrate into surrounding tissue. We are now examining the long-term implications for this system and recording efficacy for neural signals over this period. Overall, we have generated a new, injectable implant system for placing bioelectronic tissue engineered brain implants. This system has potential to promote long-term recordings and integration, while causing minimal damage at the insertion site, and provides a means for new therapeutic approaches in the brain.