(4es) Rational Design of Biointegrated Materials and Devices Towards Precise and Closed-Loop Bioelectronic Medicine

The integration of living systems with synthetic materials and devices is embedded with tantalizing possibilities. Such hybrids could allow rich information exchange with cells or specific alteration of natural tissue functions. These functionalities are the basis towards bioelectronic medicine, a new horizon that may revolutionize the way we deal with diseases. Despite substantial efforts in promoting seamless interfaces between electronic devices and biological targets, existing synthetic toolkits and fabrication techniques still cannot match the extreme structural and functional complexity of the multicellular living systems. My research aims to address this challenge by exploring new design principles of novel material synthesis and device fabrications using biological systems as a guide. With further efforts in developing new integration methods towards a biohybrid system, I aim to achieve multimodal and bidirectional interfaces down to (sub)cellular level with even cell-type specificity, which could ultimately lead to precise and closed-loop bioelectronic medicine.

Research Experience

Originally trained as a chemist, my research went far beyond chemistry, covering multiple disciplines including materials science, neuroscience and biomedical engineering. With my diverse training background, I am particularly excited about transforming breakthroughs in physical sciences and engineering into novel tools to address pressing biological questions and real-world medical challenges.

As a graduate student at the University of Chicago, I started my research career by exploring rational design principles of stimuli-responsive materials for physical modulation of biological activities, under the co-advice of Prof. Bozhi Tian (Dept. Chemistry), Prof. Francisco Bezanilla (Dept. Biochemistry and Molecular Biology), and Prof. Gordon Shepherd (Dept. Physiology at Northwestern University). Utilizing advanced characterization techniques to guide bottom-up chemical synthesis, I built a full library of silicon-based inorganic semiconducting materials with unique photo-responses, and elucidated the underlying physicochemical processes that shape the structures and properties down to atomic-scale precision. Based on these material innovations, I later demonstrated an array of novel biological applications, including the optical modulation of cellular calcium dynamics, neuronal excitability, neurotransmitter release from brain slices. With further optimization of material design and device fabrication, I was able to achieve the first successful optical control of animal activities in a non-genetic manner. Combining the advantages of electrical stimulation (i.e., non-genetic) and optogenetics (i.e., high resolution), our non-genetic optical neuromodulation method offers new opportunities to be translated to clinical treatment of neurological disorders on human patients.

During my postdoc at Stanford University, I continued to work on multiple collaborative projects to bridge electronically active materials with biological systems in a seamless manner under the guidance of Prof. Zhenan Bao (Dept. Chemical Engineering), Prof. Karl Deisseroth (Dept. Bioengineering), and Prof. Geoffrey Gurtner (Dept. Surgery), and Prof. Ivan Soltesz (Dept. Neurosurgery). In particular, I focused on the design and development of soft and conducting polymeric electronics with tissue-like electrical and mechanical properties. My research has led to the invention of the first intrinsically stretchable and high-density electrode array through a novel design of supramolecule-based topological network. The unique combination all the properties can provide cellular-scale mapping of electrophysiological activities as well as precise neuromodulation down to single nucleus level through brainstem-based brain-machine interface. Additionally, I have developed an integrated system that allows wirelessly delivery of chronically stable electroceuticals for accelerated tissue regeneration based on continuous sensing of wound physiology.

Selected Publications

1) Jiang, Y.,* Li, X.,* Liu, B.,* Yi, J., Fang, Y., Shi, F., Gao, X., Sudzilovsky, E., Parameswaran, R., Koehler, K., Nair, V., Yue, J., Guo, K., Fang, Y., Tsai, H.-M., Freyermuth, G., Wong, R. C. S., Kao, C.-M., Chen, C.-T., Nicholls, A. W., Wu, X., Shepherd, G. M. G., & Tian, B. Rational design of silicon structures for optically controlled multiscale biointerfaces, Nature Biomedical Engineering 2, 508-521 (2018). (*These authors contributed equally to this work.)

2) Jiang, Y.,* Carvalho-de-Souza, J. L.,* Wong, R. C. S.,* Luo, Z., Isheim, D., Zuo, X., Nicholls, A. W., Jung, I. W., Yue, J., Liu, D.-J., Wang, Y., De Andrade, V., Xiao, X., Navrazhnykh, L. Weiss, D. E., Wu, X., Seidman, D. N., Bezanilla, F. & Tian, B. Heterogeneous silicon-based mesostructures for phospholipid-supported transient bioelectric systems, Nature Materials 15, 1023-1030 (2016). (*These authors contributed equally to this work.)

3) Gao, X.,* Jiang, Y.,* Lin, Y.,* Kim, K.-H.,* Fang, Y., Yi, J. S., Meng, L. Y., Lee, H.-C., Lu, Z., Leddy, O., Zhang, R., Tu, Q., Feng, W., Nair, V., Griffin, P. J., Shi, F. Y., Shekhawat, G. S., Dinner, A. R., Park, H.-G., & Tian, B. Structured silicon for revealing transient and integrated signal transductions in microbial systems, Science Advances 6, eaay2760 (2020). (*These authors contributed equally to this work.)

4) Fang, Y.,* Jiang, Y.,* Ledesma, H. A.,* Yi, J., Gao, X., Weiss, D. E., Shi, F., & Tian., B. Z. Texturing Silicon Nanowires for Highly Localized Optical Modulation of Cellular Dynamics, Nano Letters 18, 4487-4492 (2018). (*These authors contributed equally to this work.)

5) Jiang, Y. & Tian, B. Inorganic semiconductor biointerfaces, Nature Reviews Materials 3, 473-490 (2018).

6) Jiang, Y.,* Parameswaran, R.,* Li, X.,* Carvalho-de-Souza, J. L.,* Gao, X., Meng, L., Bezanilla, F., Shepherd, G. M. G. & Tian, B. Nongenetic optical neuromodulation with silicon-based materials, Nature Protocols 14, 1339–1376 (2019). (*These authors contributed equally to this work.)

7) Luo, Z.,* Jiang, Y.,* Myers, B. D., Isheim, D., Wu, J., Zimmerman, J. F., Wang, Z., Li, Q., Wang, Y., Chen, X., Seidman, D. N. & Tian, B. Atomic gold-enabled three-dimensional lithography for silicon mesostructures. Science 348, 1451-1455 (2015). (*These authors contributed equally to this work.)

8) Fang, Y.,* Jiang, Y.,* Cherukara, M. J.* Shi, F., Koehler, K., Freyermuth, G., Isheim, D., Narayanan, B., Nicholls, A. W., Seidman, D. N., Sankaranarayanan, S. K. R. S., & Tian, B. Alloy-assisted deposition of three-dimensional arrays of atomic gold catalyst for crystal growth studies, Nature Communications 8, 2014 (2017). (*These authors contributed equally to this work.)

9) Zhang, Q.,* Jiang, Y.,* Chen, L., Chen, W., Li, J., Cai, Y., Ma, C., Xu, W., Lu, Y., Jia, X. & Bao Z. Ultra-Compliant and Tough Thermochromic Polymer for Self-Regulated Smart Windows, Advanced Functional Materials 31, 2100686 (2021). (*These authors contributed equally to this work.)

10) Fang, Y.,* Han, E.,* Zhang, X.-X.,* Jiang, Y.,* Lin, Y., Shi, J., Wu, J., Meng, L., Gao, X., Griffin, P. J., Xiao, X., Tsai, H.-M., Zhou, H., Zuo, X., Zhang, Q., Chu, M., Zhang, Q., Gao, Y., Roth, L. K., Bleher, R., Ma, Z., Jiang, Z., Yue, J., Kao, C.-M., Chen, C.-T., Tokmakoff, A., Wang, J., Jaeger, H. M. & Tian, B. Dynamic and Programmable Cellular-Scale Granules Enable Tissue-like Materials, Matter 2, 948-964 (2020). (*These authors contributed equally to this work.)

Teaching Interests

Throughout my research career, I was also extensively engaged in teaching at all levels. At the University of Chicago, I served as a TA for undergraduate-level Chemistry courses. At Stanford University, I did guest lectures in graduate-level courses in Materials Science and Engineering as well as Neurosurgery. I also had experiences in holding workshops and outreach events for the Physics department at UChicago and Bioengineering department at Stanford. Finally, I mentored 5 undergraduate research assistants and 8 rotation/summer students during my PhD and another 2 master students, 2 rotation/summer students during my postdoc.