Tissue-adhesive Hydrogel Optical Fiber for Peripheral Optogenetic Neuromodulation

This study developed tissue-adhesive hydrogel optical fibers for stable peripheral optogenetic neuromodulation on dynamically moving visceral organs. The fiber design combined a poly(HEMA) optical core with a tissue-adhesive PAA-PVA cladding, creating both refractive-index contrast for light confinement and wet-tissue adhesion for stable organ integration. The resulting fibers showed low optical propagation loss, maintained approximately 69% normalized light output at 30% tensile strain, retained optical performance after 10,000 loading cycles, and achieved tissue adhesion of 11.5 ± 1.8 kPa on hydrated tissue. Finite element modeling and in vivo MRI tracking showed that the adhesive fibers remained positioned on the pancreas far better than non-adhesive hydrogel optical fibers. In ChAT-ChR2 mice, the implanted fibers enabled optogenetic stimulation of pancreatic vagal innervation, increasing insulin secretion and reducing blood glucose during glucose tolerance testing. In diabetic mice, the system was integrated with continuous glucose monitoring and enabled repeated, reversible glycemic modulation over 3 days, with functional glucose-lowering responses persisting up to 14 days after implantation. Overall, the study presents a soft, adhesive hydrogel optical interface for stable light delivery to moving internal organs and demonstrates its use for optogenetic control of glucose homeostasis.