In our laboratory, we are pioneering a future in regenerative medicine that intricately weaves together the principles of soft condensed matter physics, advanced electronics, and the burgeoning field of living materials. Our mission revolves around the innovative synthesis of these domains to create biomaterials that transcend traditional limitations. By leveraging the unique properties of soft condensed matter, such as adaptability, flexibility, and responsiveness, we aim to develop materials that can intimately conform and respond to biological tissues. This approach is vital in creating dynamic bio-interfaces and soil-inspired systems that are not only biocompatible but also capable of complex interactions with living cells and tissues.
Electronics play a pivotal role in our vision, enabling us to embed intelligent functionalities into these biomaterials. By integrating soft electronics into our designs, we are pushing the boundaries of how materials communicate and interact with biological systems. This integration paves the way for advanced diagnostic tools, therapeutic devices, and bioelectronic interfaces that can monitor, stimulate, and adapt to physiological changes in real-time. Furthermore, the concept of living materials – materials that are capable of self-assembly, self-healing, and biological interaction – is central to our research ethos. We are exploring ways to imbue our materials with ‘living’ characteristics, allowing them to evolve, adapt, and even exhibit emergent behaviors in response to their environment. This innovative amalgamation of soft matter physics, electronics, and living materials is steering us toward a future where regenerative medicine is not just about repairing damage but about creating symbiotic systems that can grow, adapt, and integrate seamlessly with the human body, opening new realms of possibilities in healthcare and beyond.
A) Granules-enabled tissue-like materials
Tissues such as human skin are multicomponent and hierarchical, mechanically heterogeneous and anisotropic, self-healing, impact-absorbing, and dynamically responsive (Fig. 1A). Traditional synthetic materials, on the other hand, do not typically possess such multiscale and dynamic responsiveness. Despite extensive efforts in the biomimetics field to develop extracellular matrix (ECM)-like synthetic polymeric networks, an artificial tissue-like material that can concurrently mimic dynamic cellular- and ECM-level behaviours has yet been achieved. One major challenge is to develop cell-like building blocks that can display dynamic responses that are in synergy with the existing ECM-like polymer platforms.
In collaboration with Professor Jaeger from the University of Chicago, the Tian lab proposed that hydrated and cellular-scale granular materials can enable multiscale tissue-like behaviours in synthetic materials (Fig. 1). Due to strong intergranular interactions, dense suspensions of granular materials dynamically respond to external stress through rapid phase transformations. When integrated with synthetic hydrogel networks, the grain-embedded composite may be considered an analogue of biological tissue in terms of both structures (hierarchical assembly of cell and ECM) and properties (such as dynamic responsiveness and remodelling, and memory effect) (Fig. 1B). Using several synchrotron-based X-ray techniques, we revealed the mechanically-induced organization and training dynamics of the starch granules in the hydrogel matrix. These dynamic behaviours enable multiple tissue-like properties such as programmability, anisotropy, strain-stiffening, mechanochemistry, and self-healability. Preliminary results in my lab (manuscript in preparation) show that these tissue-like materials can significantly improve precision and biocompatibility, and bioelectronic recording, during animal surgery with a robotic device.
Figure 1. Tissue-like materials made from starch granules and hydrogels. (A) Living tissues have unique properties. (B) Granular materials can serve as a cell-like component in the hydrogel composite to enable tissue-like properties. (C) Cryo-SEM image showing the granule-hydrogel interface. (D-E) X-ray tomography images of the granules.
B) Morphing biointerfaces
Our team has developed a granule-releasing hydrogel platform, which represents a significant innovation in the field of biointerfaces. This platform marks a transition from traditional monolithic interfaces to dynamic and less invasive focal interfaces. By embedding individual granules in a responsive hydrogel matrix, we have successfully created various macroscopic shapes, such as bandages and bioelectronics/gel hybrids, which enhance manipulation at a larger scale. These granules are designed to establish focal bio-adhesions both ex vivo and in vivo, a mechanism we have elucidated through molecular dynamics simulations. Our approach effectively combines the benefits of monolithic and focal interfaces, offering a versatile solution for disease diagnosis and treatment.
In our study, we demonstrate the practical applications of this evolving hydrogel system in various medical scenarios. For instance, we have shown its effectiveness in treating ulcerative colitis, accelerating the healing of skin wounds, and reducing myocardial infarctions. Additionally, when incorporated into flexible cardiac electrophysiology mapping devices, our granule-releasing hydrogels significantly improve both device manipulation and bio-adhesion. This innovative approach not only bridges the gap between the existing monolithic and focal biointerfaces but also opens up new avenues for the development of dynamic biointerfaces in medical technology.
C) Soil-like chemical systems
We have developed a soil-inspired chemical system that is designed to modulate microbial communities and their interactions with their environment. This system, comprising nanostructured minerals, starch granules, and liquid metals, was fabricated using a bottom-up synthesis approach. We have meticulously characterized this composite, confirming its structural similarity to soil through advanced imaging techniques like 3D x-ray fluorescence, ptychographic tomography, and electron microscopy. Our team has further enhanced the system’s functionality through post-synthetic modifications using laser irradiation, creating chemical heterogeneities from the atomic to the macroscopic level. This soil-inspired material exhibits remarkable chemical, optical, and mechanical responsiveness, enabling write-erase functions in electrical performance. Moreover, we demonstrate its efficacy in enhancing microbial culture and biofilm growth, as well as boosting biofuel production in vitro.
Furthermore, our team has successfully applied this soil-inspired system in vivo, where it showed a significant impact on gut microbiota. We have observed that this material enriches gut bacteria diversity and effectively rectifies gut microbiome dysbiosis induced by tetracycline. Additionally, it has shown promising results in ameliorating colitis symptoms in rodent models with dextran sulfate sodium-induced colitis. This groundbreaking work not only demonstrates the soil-inspired system’s ability to support microbial modulation but also highlights its potential in various biological and non-biological applications. Our approach offers a new perspective in understanding and harnessing the complex interactions between microbiota and their environments, opening new avenues in the fields of ecological resilience, human health, and beyond.
Selected Publications
- Y. Fang, E. Han, X.-X. Zhang, Y. W. Jiang, Y. L. Lin, J. Y. Shi, J. B. Wu, L. Y. Meng, X. Gao, P. J. Griffin, X. H. Xiao, H.-M. Tsai, H. Zhou, X. B. Zuo, Q. Zhang, M. Q. Chu, Q. T. Zhang, Y. Gao, L. K. Roth, R. Bleher, Z. Y. Ma, Z. Jiang, J. P. Yue, C.-M. Kao, C.-T. Chen, A. Tokmakoff, J. Wang, H. M. Jaeger, B. Z. Tian, Dynamic and programmable cellular-scale granules enable tissue-like materials. Matter, 2020, 2, 948-964.
- J. Y. Shi*, Y. L. Lin*, P. J. Li, P. Mickel, C. X. Sun, K. Parekh, J. C. Ma, S. Kim, B. Ashwood, L. Y. Meng, Y. Q. Luo, S. Chen, H.-M. Tsai, C. M. Cham, J. Zhang, Z. Cheng, J. A. Abu-Halimah, J. W. Chen, P. Griffin, E. B. Chang, P. Král, J. P. Yue, B. Z. Tian. Monolithic-to-focal evolving biointerfaces in tissue regeneration and bioelectronics. Nature Chemical Engineering, 2023, accepted.
- Y. L. Lin*, X. Gao*, J. P. Yue*, Y. Fang*, J. Y. Shi, L. Y. Meng, C. Clayton, X.-X. Zhang., F. Y. Shi, J. J. Deng, S. Chen, Y. Jiang, F. Marin, J. T. Hu, H.-M. Tsai, Q. Tu, E. W. Roth, R. Bleher, X. Q. Chen, P. Griffin, Z. H. Cai, A. Prominski, T. W. Odom, B. Z. Tian. A Soil-Inspired Dynamically Responsive Chemical System for Microbial Modulation. Nature Chemistry, 2022, DOI: 10.1038/s41557-022-01064-2. Link