Xinyue Liu1,2,Siyuan Rao3,2,Weixuan Chen3,Kayla Felix3,Jiahua Ni2,Atharva Sahasrabudhe2,Shaoting Lin1,2,Qianbin Wang3,Yuanyuan Liu4,Zhigang He5,Polina Anikeeva2,Xuanhe Zhao2
Michigan State University1,Massachusetts Institute of Technology2,University of Massachusetts Amherst3,National Institutes of Health4,Harvard University5
Xinyue Liu1,2,Siyuan Rao3,2,Weixuan Chen3,Kayla Felix3,Jiahua Ni2,Atharva Sahasrabudhe2,Shaoting Lin1,2,Qianbin Wang3,Yuanyuan Liu4,Zhigang He5,Polina Anikeeva2,Xuanhe Zhao2
Michigan State University1,Massachusetts Institute of Technology2,University of Massachusetts Amherst3,National Institutes of Health4,Harvard University5
We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.09 dB cm<sup>-1</sup>, Young’s modulus of 1.6 MPa, stretchability of 200%, and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel optical fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an eight-week period. Our hydrogel optical fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation with implications in motor recovery and pain management.