A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo

Abstract

Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality. In this study, we utilized an atomic layer deposition (ALD) technique to generate an inorganic, silicon dioxide (SiO₂) coating layer on chemically cross-linked PVA hydrogel fibers. To evaluate the stability of SiO₂-coated PVA hydrogel fibers mimicking the in vivo environment, we conducted accelerated stability tests. SiO₂-coated PVA hydrogel fibers showed improved stability over a one-week incubation period under a harsh environment, preventing swelling and preserving their mechanical and optical properties compared to uncoated fibers. These SiO₂-coated PVA hydrogel fibers demonstrated nanoscale polymeric crystalline domains (6.5 ± 0.1 nm), an elastic modulus of 73.7 ± 31.7 MPa, a maximum elongation of 113.6 ± 24.2%, and minimal light transmission loss (1.9 ± 0.2 dB cm⁻¹). Lastly, we applied these SiO₂-coated PVA hydrogel fibers in vivo to optically activate the motor cortex of transgenic Thy1::ChR2 mice during locomotor behavioral tests. This mouse cohort was genetically modified to express the light-sensitive ion channel, channelrhodopsin-2 (ChR2), and implanted with hydrogel fibers to deliver light to the motor cortex area (M2). Light stimulation via hydrogel fibers resulted in optogenetically modulated mouse locomotor behaviors, including increased contralateral rotation, mobility speeds, and travel distances.