RESUMEN
Abstract: The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells-the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes. Flexible TNAs-on-polyimide sustained a linear release of anti-inflammatory dexamethasone up to ~11 days under different bending conditions. Finally, microfabrication processes for patterning and transferring TNA microsegments were developed to facilitate structural stability during device flexing and to expand the set of compatible polymer substrates. The techniques developed in this study can be applied to integrate TNAs or other similar nanoporous inorganic films onto various polymer substrates. Impact statement: Titania nanotube arrays (TNAs) are highly tunable and biocompatible structures that lend themselves to multifunctional implementation in implanted devices. A particularly important aspect of titania nanotubes is their ability to serve as nano-reservoirs for drugs or other therapeutic agents that slowly release after implantation. To date, TNAs have been used to promote integration with rigid, dense tissues for dental and orthopedic applications. This work aims to expand the implant applications that can benefit from TNAs by integrating them onto soft polymer substrates, thereby promoting compatibility with soft tissues. The successful direct growth and integration of TNAs on polymer substrates mark a critical step toward developing mechanically compliant implantable systems with drug delivery from nanostructured inorganic functional materials. Diffusion-driven release kinetics and the high drug-loading efficiency of TNAs offer tremendous potential for sustained drug delivery for scientific investigations, to treat injury and disease, and to promote device integration with biological tissues. This work opens new opportunities for developing novel and more effective implanted devices that can significantly improve patient outcomes and quality of life. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-023-00628-y.
RESUMEN
Intracortical microelectrodes (IMEs) can be used to restore motor and sensory function as a part of brain-computer interfaces in individuals with neuromusculoskeletal disorders. However, the neuroinflammatory response to IMEs can result in their premature failure, leading to reduced therapeutic efficacy. Mechanically-adaptive, resveratrol-eluting (MARE) neural probes target two mechanisms believed to contribute to the neuroinflammatory response by reducing the mechanical mismatch between the brain tissue and device, as well as locally delivering an antioxidant therapeutic. To create the mechanically-adaptive substrate, a dispersion, casting, and evaporation method is used, followed by a microfabrication process to integrate functional recording electrodes on the material. Resveratrol release experiments were completed to generate a resveratrol release profile and demonstrated that the MARE probes are capable of long-term controlled release. Additionally, our results showed that resveratrol can be degraded by laser-micromachining, an important consideration for future device fabrication. Finally, the electrodes were shown to have a suitable impedance for single-unit neural recording and could record single units in vivo.
RESUMEN
(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n = 6) or smooth control (n = 6) probes, and their recording performance was evaluated over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated an increased impedance and noise floor compared to controls. However, the recording performances of the nanopatterned and smooth probes were similar, with active electrode yields for control probes and nanopatterned probes being approximately 50% and 45%, respectively, by 4 weeks post-implantation. Gene expression analysis showed one gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: this study provides a foundation for investigating novel nanoscale topographies on neural probes.