2004425 (1 of 17) © 2020 Wiley-VCH GmbH www.advmat.de PROGRESS REPORT 3D Interfacing between Soft Electronic Tools and Complex Biological Tissues Hegeng Li, Hongzhen Liu, Mingze Sun, YongAn Huang,* and Lizhi Xu* H. Li, H. Liu, M. Sun, Prof. L. Xu Department of Mechanical Engineering The University of Hong Kong Hong Kong SAR 999077, China E-mail: xulizhi@hku.hk H. Li, Prof. Y. A. Huang State Key Laboratory of Digital Manufacturing Equipment and Technology Huazhong University of Science and Technology Wuhan 430074, China E-mail: yahuang@hust.edu.cn The ORCID identifcation number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202004425. DOI: 10.1002/adma.202004425 Essential to these tissue-like electronic devices are the constituent soft materials and their fabrication techniques. Polymers and composites provide intrinsic toler- ance to strain. [2] Inorganic nanostruc- tures impart high electronic properties without compromising the deformability at the device level. [3] Methods adapted from microelectronic manufacturing pro- vide available routes for patterning and integration of these materials into hybrid systems. However, as exemplifed by wafer-based thin-flm deposition, photoli- thography, and etching, the typical fabrica- tion processes are designed primarily for planar devices. Consequently, electronics involving soft constituents mostly remain with 2D features, with a typical form resembling a plastic sheet. These devices are capable of integration over a small area on the human body with low topographic variation. For instance, small electronic patches are usually laminated on the forearm for the measure- ment of temperature, pulse wave, bioelectricity and/or blood oxygenation, providing medical utilities. [4] However, the human body involves many important organs with structural complexity far beyond the intrinsic features of electronic sheets. For instance, the brain involves billions of neu- rons interconnected in the highly folded cerebral cortex, which cannot be accurately mapped with only a planar device. More- over, the neuronal activities take place not only on the surface but also in the deep layers of the brain, creating difculties for brain–machine interfacing. The heart involves four muscular chambers with highly dynamic structures. The electromechan- ical coupling in a complex 3D fashion makes cardiac electronic interfaces challenging. Although the stifness and elasticity of soft electronics could match those of the natural tissues, their physical embodiment as 2D sheets may hinder advanced integra- tion on the brain, the heart, and other sophisticated 3D organs. In this Progress Report, we highlight some of the recent strategies on transforming soft electronic tools for building 3D biointerfaces. We start with a brief overview on soft electronic materials. The materials toolbox enables various deformation mechanisms, which is essential for 3D architecture of soft devices. The discussion expands on a range of 3D electronic systems for biomedical applications. For devices integrated on the contoured organ surfaces, mesh structures and those inspired by kirigami are useful for creating conformal contact. When guided by 3D imaging and modeling of the target organs, devices could be fabricated with specifc features matching Recent developments in soft functional materials have created opportunities for building bioelectronic devices with tissue-like mechanical properties. Their integration with the human body could enable advanced sensing and stimulation for medical diagnosis and therapies. However, most of the available soft electronics are constructed as planar sheets, which are difcult to interface with the target organs and tissues that have complex 3D structures. Here, the recent approaches are highlighted to building 3D interfaces between soft electronic tools and complex biological organs and tissues. Examples involve mesh devices for conformal contact, imaging- guided fabrication of organ-specifc electronics, miniaturized probes for neurointerfaces, instrumented scafold for tissue engineering, and many other soft 3D systems. They represent diverse routes for reconciling the interfacial mismatches between electronic tools and biological tissues. The remaining challenges include device scaling to approach the complexity of target organs, biological data acquisition and processing, 3D manufacturing techniques, etc., providing a range of opportunities for scientifc research and technological innovation. 1. Introduction The past decade witnessed a rapid development of soft elec- tronic devices with mechanical characteristics approaching those of soft biological tissues. [1] Unlike traditional electronics based on rigid semiconductor chips and circuit boards, these soft devices possess Young’s moduli at the levels ranging from kPa to GPa, with a reversible elongation of up to 100%. They could minimize the mechanical mismatch at the biotic–abiotic interface, enabling a variety of sensors and stimulators for continuous health monitoring, interventional therapies, fun- damental physiological investigation, tissue engineering, and many other applications. Adv. Mater. 2020, 2004425