The Future of Neuroimplantable Devices: A Materials Science and Regulatory Perspective

Abstract

The past two decades have seen unprecedented progress in the development of novel materials, form factors, and functionalities in neuroimplantable technologies, including electrocorticography (ECoG) systems, multielectrode arrays (MEAs), Stentrode, and deep brain probes. The key considerations for the development of such devices intended for acute implantation and chronic use, from the perspective of biocompatible hybrid materials incorporation, conformable device design, implantation procedures, and mechanical and biological risk factors, are highlighted. These topics are connected with the role that the U.S. Food and Drug Administration (FDA) plays in its regulation of neuroimplantable technologies based on the above parameters. Existing neuroimplantable devices and efforts to improve their materials and implantation protocols are first discussed in detail. The effects of device implantation with regards to biocompatibility and brain heterogeneity are then explored. Topics examined include brain‐specific risk factors, such as bacterial infection, tissue scarring, inflammation, and vasculature damage, as well as efforts to manage these dangers through emerging hybrid, bioelectronic device architectures. The current challenges of gaining clinical approval by the FDA—in particular, with regards to biological, mechanical, and materials risk factors—are summarized. The available regulatory pathways to accelerate next‐generation neuroimplantable devices to market are then discussed.

Foreign body responses in central nervous system mimic natural wound responses and alter biomaterial functions

“…In this study we used hydrogels as surrogate biomaterials to characterize host responses to specifically presented chemical functionalities, and molecular delivery from hydrogels was the primary functional outcome measure evaluated. The basic principles we identified can inform the development of materials for a variety of CNS applications including implantable neuroprostheses for recording and stimulating neural circuit activity [2,3,23,68]. For example, we show that surface charge at the materialhost interface influences the severity of FBRs, which in turn will influence the degree of protective fibrotic and astrocyte barrier formation that forms to isolate the materials from adjacent neural tissue and may thereby attenuate function.…”

“…Biomaterials are under widespread investigation for experimental and therapeutic applications in the central nervous system (CNS) [1]. Biomaterials with specialized properties have been incorporated in implantable neuroprostheses that are used clinically for recording neuronal activity and stimulating neural circuits in the CNS [2,3]. In addition, injectable biomaterial hydrogels are used extensively as experimental tools to provide local delivery of growth factors for example to attract injured and regenerating axons to grow across CNS lesions [4,5] as well as to afford molecular and physical support to co-suspended neural progenitor cells (NPC) to improve survival and modulate differentiation upon grafting into the CNS [6][7][8].…”

Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions

“…In this study, we used hydrogels as surrogate biomaterials to characterize host responses to specifically presented chemical functionalities, and molecular delivery from hydrogels was the primary functional outcome measure evaluated. The basic principles we identified can inform the development of materials for a variety of CNS applications including implantable neuroprostheses for recording and stimulating neural circuit activity 2,3,23,70 . For example, we show that surface charge at the material-host interface influences the severity of FBRs, which in turn will influence the degree of protective fibrotic and astrocyte barrier formation, which serves to isolate the materials from adjacent neural tissue and may thereby attenuate function.…”

“…iomaterials are under widespread investigation for experimental and therapeutic applications in the central nervous system (CNS) 1 . Biomaterials with specialized properties have been incorporated in implantable neuroprostheses that are used clinically for recording neuronal activity and stimulating neural circuits in the CNS 2,3 . In addition, injectable biomaterial hydrogels are used extensively as experimental tools to provide local delivery of growth factors, for example, to attract injured and regenerating axons to grow across CNS lesions 4,5 as well as to afford molecular and physical support to co-suspended neural progenitor cells to improve survival and modulate differentiation upon grafting into the CNS [6][7][8] .…”

Flow driven robotic navigation of microengineered endovascular probes

“…However, the majority of the brain is still inaccessible because the existing tools are bulky, and navigating through the minuscule and tortuous cerebral vasculature without causing tissue damage is extremely challenging. While technological progress in microengineering has introduced a variety of microdevices that can perform optical, thermal, electrical and chemical interrogation and modulation of the nervous system [8][9][10][11][12][13][14][15] , conventional navigation techniques are incapable of transporting miniaturized tethered devices deep into the microvasculature primarily due to mechanical limitations. The invention of a methodology that provides rapid and safe passage for microdevices regardless of the complexity of the trajectory may become instrumental for translational medicine and neuroscience research.…”