ABSTRACT
Neural implants that are based on mechanically adaptive polymers (MAPs) and soften upon insertion into the body have previously been demonstrated to elicit a reduced chronic tissue response than more rigid devices fabricated from silicon or metals, but their processability has been limited. Here we report a negative photoresist approach towards physiologically responsive MAPs. We exploited this framework to create cross-linked terpolymers of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate and 2-ethylhexyl methacrylate by photolithographic processes. Our systematic investigation of this platform afforded an optimized composition that exhibits a storage modulus E' of 1.8 GPa in the dry state. Upon exposure to simulated physiological conditions the material swells slightly (21% w/w) leading to a reduction of E' to 2 MPa. The large modulus change is mainly caused by plasticization, which shifts the glass transition from above to below 37 °C. Single shank probes fabricated by photolithography could readily be implanted into a brain-mimicking gel without buckling and viability studies with microglial cells show that the materials display excellent biocompatibility.
Subject(s)
Biocompatible Materials/chemistry , Polyhydroxyethyl Methacrylate/chemistry , Tissue Scaffolds/chemistry , Acrylates/chemistry , Cell Culture Techniques , Cell Proliferation , Cross-Linking Reagents/chemistry , Humans , Mechanical Phenomena , Methacrylates/chemistry , Microglia/cytology , Phase Transition , Photochemical Processes , Prostheses and Implants , Stereolithography , Tissue Engineering , Transition TemperatureABSTRACT
OBJECTIVE: The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. APPROACH: In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. MAIN RESULTS: Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. SIGNIFICANCE: Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems.
