24 Oct 2023
Implantable hydrogel allows optogenetic modulation of nerves in freely moving animals.MIT has developed optical fibers soft and flexible enough to be implanted into a living subject and stretch with its movements without failing.
This could offer a route to delivering light to major nerves throughout the body for optogenetic modulation, whereby light is used to fire or inhibit specific neurons labelled with light-activated enzymes.
As described in Nature Methods, the MIT research helps tackle a shortcoming of conventional optical fibers used for optogenetic purposes. In many cases the modulus and limited elasticity of the fiber hinders its implantation adjacent to peripheral nerves that experience large deformations.
This hurdle is one reason why optogenetics has so far been primarily employed in the brain, noted the MIT project. Since that area lacks pain receptors, rigid devices can be implanted relatively easily, although even there the fiber's rigidity can then damage the neural tissues of interest.
The MIT team wondered whether more suitable fibers could help to apply optogenetic techniques to nerves outside the brain, allowing them to be used in studies of sciatica, motor neuron disease, or general numbness and pain.
"Current devices used to study nerve disorders are made of stiff materials that constrain movement, so that we can’t really study spinal cord injury and recovery if pain is involved," commented MIT's Siyuan Rao. "Our new fibers can adapt to natural motion and do their work while not limiting the motion of the subject. That can give us more precise information."
The breakthrough involved the manufacture of a soft, stretchable, transparent optical fiber, made from a hydrogel whose recipe was tuned to create nanoscale polymer crystals scattered throughout a more flexible "Jell-O-like" solution. The fiber's core and cladding layers were given a different refractive index, through control of the nanoscale crystal arrangement inside each layer.
Sciatic nerves and major organs
MIT has previously studied how hydrogel materials could be used as novel materials in biomedical optics, as in the 2016 research into the fundamentals of using hydrogel materials as optical fibers. That project, from the MIT lab of Xuanhe Zhao who also co-authored the new report, envisaged materials suitable for optogenetics as well as other in-body uses, such as stretchable strain-sensor fibers implanted along the length of a patient's limb.
In the new study, trials were carried out using mice with sciatic nerves optogenetically modified so that blue light would excite neural activity and yellow light would inhibit it. After initial implantation of the softer fibers MIT found that the mice were still able to run freely on a wheel, and after a further two months the fiber was still robust and could transmit light efficiently.
Using standard laboratory procedures for assessing pain inhibition, MIT then observed that delivering yellow light via the fiber made the mice much less sensitive to pain than rodents that were not stimulated with light, with sciatic pain being significantly inhibited.
Having tested the fibers for the study of sciatic nerves, MIT believes the new technology could be tailored for implantation in peripheral nerves or other motile organs, such as the heart, gut and blood vessels.
"We are focusing on the fiber as a new neuroscience technology," said researcher Xinyue Liu. "We hope to help dissect mechanisms underlying pain in the peripheral nervous system. With time, our technology may help identify novel mechanistic therapies for chronic pain and other debilitating conditions such as nerve degeneration or injury."