Dr. Xinyue Liu is an Assistant Professor at Michigan State University in the department of Chemistry and Materials Science. She leads the Liu Research Group for soft and adaptive materials to create solutions for issues of human health and climate change.
Q: Can you give an overview of the research that takes place in your lab and its importance?
A: My lab has developed soft and implantable fibers that can deliver light to major nerves through the body. When these nerves are genetically modified to respond to light, the fibers can send pulses of light to the nerves to either stimulate the muscle contraction or inhibit pain. The optical fibers are flexible and stretch with the body even when the body is moving or eating.
The newly developed fibers are meant as an experimental tool that can be used by scientists to explore the causes and potential treatments for peripheral nerve disorders in animal models. Peripheral nerve pain can occur when nerves outside the brain and spinal cord are damaged, resulting in tingling, numbness and pain in affected limbs. Peripheral neuropathy is estimated to affect more than 20 million people in the US.
Q: What do you want to achieve with your research?
A: The key motivation for this particular study is to apply optogenetics to the dynamic tissues in the body. Optogenetics is a powerful genetic tool that can turn on or off certain neural cells when shining light on top of them. It has been widely used in neuroscience to investigate how different cells in the brain and nervous system function and how their activity can be modulated.
However, one of the biggest challenges in applying optogenetics is the delivery of light to peripheral nerves that experience mechanical strain during locomotion. Traditional light-delivery devices made from rigid materials, such as glass fibers, are not well-suited for this purpose. They can impede the natural behaviors of animals and may cause tissue damage when used in dynamic conditions. Vice versa, the natural locomotion of animals will apply repeated mechanical strain on the implanted light-delivery devices, leading to the rupture of the silica fibers. Thus, we want to seek materials that can effectively deliver light to peripheral nerves in naturally behaving animals.
Tech Talks: Essentially, the materials must be able to adapt to the movements of the animal. While in this situation, a reactive solution is being researched, in the sense that the material must react to movement, a similar scenario was brought up in our interview with Dr. Chestek. Trying to translate brain signals more efficiently to prosthetic arm movement, Dr. Chestek’s lab utilized neural networks to optimize movement and predict signals.
Q: What do you see as the next step in your research?
A: Currently, we tested our fiber to optically control the sciatic nerves in small animals – mice – with only one color of light. For the next step, we are exploring methods for scaling up the fabrication of the soft optical fibers, which might fit the scope of large animals and even primates. In addition, due to the multiplexed nature of optical transmission, future research can focus on light delivery with different wavelengths, which independently modulate specific neuron cell populations. Lastly, our findings indicate the possibility of applying the light delivery technique with soft fibers to other mobile organs beyond peripheral nerves, such as the heart and gastrointestinal system, through customized fiber designs.
Q: What discoveries and innovations have led to your current work?
A: To address the challenges in peripheral optogenetics, we aimed to develop an alternative approach using hydrogels. Hydrogels are soft and have a high water content. In addition, it shows tunable mechanical properties and optical transparency in the visible light range, making them promising candidates for delivering light to peripheral nerves during locomotion. However, traditional hydrogels are susceptible to fatigue fracture from repeated deformation during animal movement.
Our key innovation is that we control the growth of polymeric nanocrystalline domains to enable the optimized optical and mechanical properties and generate fatigue-resistant hydrogel optical fibers. The fatigue-resistant hydrogel fibers we developed can withstand locomotion strain across more than 30,000 fiber stretch cycles and allow the light transmitting through it with minimal absorption, scattering, and interfacial leakage.
Q: What did the procedure look like for deciding what materials to use? What previous research may have guided this?
A: We engineered the optical and mechanical properties of hydrogels through the controlled growth of polymeric nanocrystalline domains. This approach enabled the creation of fatigue-resistant hydrogels that exhibit high transmittance and a high refractive index, even under continuous deformation. Specifically, we constructed a hydrogel-based optical fiber comprising a core–cladding structure with poly(vinyl alcohol) hydrogels of different refractive indices. At the fiber’s distal end, a hydrogel cuff was added to encase the sciatic nerve. By leveraging annealing and crosslinking strategies during hydrogel fabrication, we engineered the nanocrystalline domains for optimal light absorption, scattering and refractive properties. For example, we introduced more nanocrystalline domains into the hydrogel optical core to ensure that its refractive index exceeded those of the hydrogel cladding and body fluid, confining the light within the hydrogel core. Additionally, these nanocrystalline domains contributed to mechanical resilience (with a fatigue strength of 1.4 MPa against 30,000 stretch cycles) during repeated fiber stretching.
We have worked on soft materials with fatigue resistance for a few years. Now we adopted the material innovations and created an implantable device for long-term optogenetic control.
Q: What implications does your results have for other projects that you are working on or other work of researchers in your field?
A: This is a platform technology that can be further expanded to integrate multiple functionalities and target different neural circuits. The demonstration of robust long-term functionality over a period of several weeks highlights the broad impact of this technology on studies in freely behaving animals.
Tech Talks: This platform and similar work shows the future of treatments and medical technologies that do not impede lifestyle or time. Rather than being forced to keep a limb from moving while being treated, this treatment allows for free movement in day-to-day life. Another example of this is in Dr. Xuanhe Zhao’s research, a supporting researcher in this project, with the creation of wearable ultrasound devices to constantly monitor the progression of disease treatment while patients live their lives.
Q: What were the main obstacles you faced in your lab and what intricacies did you have to be aware of?
A: One of the most common obstacles for many labs including mine is securing adequate funding for research. Budget restrictions can limit the scope of experiments, the purchase of necessary equipment, or the hiring of intelligent scientists and engineers. As a junior faculty, I am spending half of my time on education and research. Another half of time is on writing proposals.
In addition to that, I am now recruiting students in my lab. Students who are interested in our research have different educational backgrounds, including chemistry, mechanical engineering, biomedicine or even botany. While this diversity is a wellspring of innovative ideas, it’s imperative for me to foster seamless communication across these varied fields. It’s equally vital to ensure that each student is aligned with a research project where their unique expertise shines and contributes meaningfully.
Q: What kind of response have you gotten for your research, both in the medical sector and from the general population?
A: People specializing in neuroscience and optics showed great interest given the adaptability of the soft fibers in dynamic conditions. Clinicians and medical researchers were intrigued by its application in pain management, which suggests a potential therapeutic avenue for various neural disorders.
Q: Do you believe your research will be implemented by doctors soon, and what relations Do you have with medical professionals considering the topics of your research?
A: However, I would like to clarify that optogenetics, while a powerful and promising research tool, had not yet fully transitioned to widespread clinical use. It was primarily being employed in laboratory and preclinical studies to better understand neural circuits and functions. Clinical translation and the application of optogenetics in human healthcare were still in the early stages, due to the safety and ethical considerations. For now, we use this technology to help understand the nociceptive circuits and help develop new therapies.
Q: How do you involve students in your lab, and what type of experiences do they have? Do you prioritize having them experience, learn certain concepts, etc?
This question might go to Professor Xuanhe Zhao at the Massachusetts Institute of Technology, instead of me. But in Michigan State University, we have very diverse outreach that involve K-12 and high school students. In the annual science festival, all local students (from K-12 to graduate students) and their parents are encouraged to attend the activities, including hands-on experiences.
Tech Talks: Many local universities and labs will host events like the aforementioned one. While they might not be widely advertised, try searching for programs that cater to your scientific and research interests. Researchers are always open to fostering the next generation of scientists!