Biomaterial strategies towards the development of next generation neural prosthetic devices.

摘要

Despite recent advances, there are major hurdles to overcome before cortical neural prosthetics can become a viable therapeutic strategy. The injury response to the insertion of these devices results in eventual loss of recorded neuronal signal, preceded by inflammatory responses in the form of microglia, astrocyte, and macrophage aggregation at the injury site. Within days, gliosis, the glial encapsulation of the probe, excludes neurons and instigates progressive localized neurodegeneration. Variations in probe composition and designs are being investigated to enhance probe viability but the end result remains. In this work, two efforts were employed to resolve the problem of gliosis and its long-term consequences.;Strategies integrating disciplines of chemistry, biology and engineering were employed to explore methods to advance the field of invasive cortical devices. The first effort involved the development of ultrafast degrading and ultrafast resorbing polymers based on a new family of tyrosine-derived polycarbonate terpolymers. Such polymers can enable the insertion of micronized devices into brain parenchyma, and once inserted, the polymers degrade and resorb in a benign manner, thus minimizing the acute response to the injury. The clinical relevance of such materials is the ability to insert devices that are smaller than the nominal size of neuronal soma, thus possibly relieving the probe from a chronic glial response. Various polymer chemistries were synthesized and characterized in vitro. Quantified analysis of the glial and neural response to the presence of the polymer in rat brain tissue confirmed our hypothesis of reduction in glial response when ultra-fast degrading and resorbing polymers are used. The retention of recording functionality of microelectrodes coated with this polymer, and its ability to deliver anti-inflammatory agents locally to the site of insertion were quantified as well.;The second project is the development of completely new materials for use in neural electrodes. Current devices are either silicon or metal based. We developed carbon nanotube-polysaccharide composites. These materials have proven to be readily fabricated as microwires. Mechanical characterization showed the microwires are stiff when dry (allowing insertion) but soft and compliant when hydrated (for brain tissue compatibility). They are electrically conductive, and can be easily made bioactive through chemical conjugation of biologically active moieties, thus affecting cell-material interactions. The morphological, electrical, and biological properties of these novel materials were characterized for their potential to perform as neural electrodes. The effect of insertion of such materials into brain parenchyma has resulted in minimal glial response, while brain cell attachment could be altered through the conjugation of extracellular matrix proteins with the carbon nanotube-polysaccharide composite. Thus, future designs of neural prosthetics could highly benefit from the employment of such novel nanocomposites.