Fabrication of Site‐Specific 3D Structures via Macroscopic Supramolecular Assembly for Spatially Controlled Alignment of Multiple Cells

Abstract The self‐assembly of micrometer‐to‐millimeter components, referred to as “macroscopic supramolecular assembly (MSA),” offers an efficient approach for constructing cell‐scale 3D bioactive structures with flexible modular designs. Compared with available 3D bio‐printing or conventional modular assembly of cell‐material units, MSA is advantageous in decoupling material preparation and cell loading processes by directing cell adhesion after the preparation of 3D structures, which minimizes the trade‐off between cell viability and material selection. But the challenge lies in efficient self‐sorting of different cells and spatially controlled cell distribution. Hence, MSA is combined with the surface chemistry of orthogonally specific peptides to different cells and magnetic manipulation, and fabricated 3D bioactive structures that direct cell sorting. Microscale polydimethylsiloxane (PDMS) components are modified with 1) Arg‐Glu‐Asp‐Val and Val‐Ala‐Pro‐Gly peptides affinitive to endothelial cells (ECs) and smooth muscle cells (SMCs), respectively, and 2) host/guest molecules as “supramolecular glues” for precise structuring and interfacial bonding. Self‐sorting and spatially controlled adhesion of ECs and SMCs is achieved to mimic layered vascular structures. This “Lego‐like” strategy is free of compromising cell viability with structure design, thus contributing to spatially intricate and bioactive 3D architectures, and promoting the development of MSA from fundamental advances to applications.