Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and
stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device
performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis
or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering,
and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics
technology into long-term clinical use. This article draws connections between specific challenges faced by current
neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within
the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity
are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors,
three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural
stem/progenitor cell biology. Finally, recent insights gained from the fields of developmental neurobiology and
cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration
toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.