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Page 12 of 30 Kim et al. Soft Sci 2023;3:16 https://dx.doi.org/10.20517/ss.2023.07

Bio-medical devices
Accurate monitoring of the physiological properties of 3D biological systems can improve our
understanding of the evolution and origin of abnormal behaviors or disease states [180,181] , as well as the
interactions associated with the development of neural systems [182-184] . Furthermore, an in-depth analysis of
soft living tissues can serve as the basis for diagnosing and treating diseases [185-187] . Thus, the integration of
traditional medical technology and biological systems can establish pathways to improve health and prolong
life [188-190] . However, biological systems, including plants (e.g., stems and seeds) and animals (e.g., hearts,
brains, and blood vessels), have mostly complex 3D curved surfaces, some with dynamic and time-varying
features. Nevertheless, many biomedical technologies have rigid, planar, and 2D shapes, which limit their
functional interfaces to localized areas of 3D structures, near the bottom contact surface. In this regard, the
development of fabrication approaches to allow conformal contact of biomedical systems with 3D biological
surfaces is important for highly reliable information interactions between them. In addition, as physical
coupling, it is necessary to enable complex optical/electrical/chemical exchange between abiotic and
biological systems. In this chapter, we introduce several studies that have developed 3D biomedical systems
and demonstrated various applications such as health monitoring, human-machine interfaces, therapeutic
devices, artificial tissues/organs, and basic biomedical research [Figure 6].

Yang et al. demonstrated the stable attachment of millimeter-scale flexible electronic/optoelectronic
systems, such as wireless cardiac pacemakers and multielectrode epicardial arrays, to vital internal organs
[105]
with bioelectronics-tissue interface materials (BTIMs) [Figure 6A] . BTIMs are mechanically compliant,
conductive, and optically transparent and have chemically controlled bioabsorption rates, allowing them to
bond strongly to both device and internal organ surfaces with long-term stability. Skylar-Scott et al.
reported a biological manufacturing method of assembling organ-building blocks into living matrices with a
high cellular density [Figure 6B] . Perfusable vascular channels in living matrices were introduced
[191]
through 3D bioprinting. They could fabricate the arterial vascular network geometry within a cardiac tissue
matrix using a patient-specific, cardiac structural model. Xue et al. assembled a tiny 3D rhomboid ribbon
microscale structure with a lateral feature size of a sulcus [Figure 6C] . Although the complex sulcus
[192]
topology exhibited obvious bending/torsional deformation during assemblies of 3D electronic systems, a
quantitative mechanical modeling strategy was used to transform curved elastomer substrates into planar or
cylindrical configurations. Gu et al. introduced a scalable platform employing a 3D high-performance field
effect transistor (FET) array obtained through buckling at predesigned hinge locations of a 2D precursor
[193]
[Figure 6D] . The 3D FET array enables accurate recording of transmembrane potentials in electrogenic
cells with minimally invasive cellular interfacing and revealing signal conduction paths in cardiac muscle
tissue constructs via intracellular recordings. Chen et al. fabricated 3D biomimetic cell-laden
microstructures that could mimic the 3D hierarchical structure of the native tissue using engineered tissue
[194]
models and the compressive buckling method [Figure 6E] . By incorporating 2D microfabrication
methods into 3D cellular engineering, the proposed method shows the possibility of solving problems such
as low spatial resolution, cell viability, and the limited choice of bioink due to conventional 3D bioprinting.
Yan et al. fabricated a biomimetic, artificial soft 3D network system using helical microstructures as
building blocks, which connect lattice nodes [Figure 6F] . The developed system exhibited
[195]
defect-insensitive and J-shaped stress-strain responses, which are closely matched with those of real
biological tissues. These findings are expected to provide many opportunities for flexible bio-integrated
applications. Park et al. introduced microfabricated 3D frameworks as multifunctional neural interfaces that
simultaneously include electrical, optical, chemical, and thermal interfaces to cortical spheroids, organoids,
and assembloids [Figure 6G] . The 3D complex architecture could exploit reversible engineering control
[196]
over shapes, sizes, and geometries to match organoids/spheroids of interest. It is expected that this platform
will improve our understanding of basic neuroscience such as the formation and regrowth of bridging
tissues across a pair of spheroids. Huang et al. developed miniaturized wafer-integrated multielectrode array