Three dimensional bioelectronic interfaces to small-scale biological systems

[Display omitted] •Advanced bioelectronics technologies enable interfaces to 3D biological systems.•3D electronic scaffolds integrate into biological tissues.•3D electronic frameworks integrate onto biological tissues.•Multimodal operation creates vast opportunities for biological research. Recent advances in bio-interface technologies establish a rich range of electronic, optoelectronic, thermal, and chemical options for probing and modulating the behaviors of small-scale three dimensional (3D) biological constructs (e.g. organoids, spheroids, and assembloids). These approaches represent qualitative advances over traditional alternatives due to their ability to extend broadly into volumetric spaces and/or to wrap tightly curved surfaces of natural or artificial tissues. Thin deformable sheets, filamentary penetrating pins, open mesh structures and 3D interconnected networks represent some of the most effective design strategies in this emerging field of bioelectronics. This review focuses on recent developments, with an emphasis on multimodal interfaces in the form of tissue-embedding scaffolds and tissue-surrounding frameworks.