Liu Yuchen, Ming Rui, Zhang Qian, Wang Yuguang, Liu Yijing, Galyametdinov Yuriy G, Knyazev Andrey, Shi Feng, Liu Fang, Cheng Mengjiao
State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Centre for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
Department of General Dentistry II, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, No.22, Zhongguancun South Avenue, Haidian, Beijing, 100081, China.
Adv Sci (Weinh). 2025 Sep;12(33):e02425. doi: 10.1002/advs.202502425. Epub 2025 Aug 11.
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.
微米级到毫米级组件的自组装，即“宏观超分子组装（MSA）”，为构建具有灵活模块化设计的细胞尺度三维生物活性结构提供了一种有效方法。与现有的三维生物打印或细胞-材料单元的传统模块化组装相比，MSA的优势在于通过在三维结构制备后引导细胞黏附，将材料制备和细胞加载过程解耦，从而最大限度地减少细胞活力与材料选择之间的权衡。但挑战在于不同细胞的高效自分选和空间控制的细胞分布。因此，MSA与针对不同细胞的正交特异性肽的表面化学以及磁操控相结合，制造出了能够引导细胞分选的三维生物活性结构。微米级聚二甲基硅氧烷（PDMS）组件用1）分别对内皮细胞（ECs）和平滑肌细胞（SMCs）具有亲和力的精氨酸-谷氨酸-天冬氨酸-缬氨酸和缬氨酸-丙氨酸-脯氨酸-甘氨酸肽，以及2）作为“超分子胶水”用于精确构建和界面结合的主/客体分子进行修饰。实现了ECs和SMCs的自分选和空间控制黏附，以模拟分层血管结构。这种“类乐高”策略不会因结构设计而损害细胞活力，从而有助于构建空间复杂的生物活性三维结构，并推动MSA从基础进展向应用发展。
