Kim, Kanghyeon Min, Sunhong Thangam, Ramar Tag, Kyong-Ryol Lee, Hyun-Jeong Heo, Jeongyun Jung, Hwapyung Swe, Thet Thet Zare, Iman Song, Guosheng Najafabadi, Alireza Hassani Lee, Junmin Jung, Hyun-Do Kim, Jong Seung Hur, Sunghoon Song, Hyun-Cheol Park, Sung-Gyu Zhang, Kunyu Zhao, Pengchao Bian, Liming Kim, Se Hoon Yoon, Juyoung Ahn, Jae-Pyoung Kim, Hong-Kyu Kang, Heemin 2025-03-19T14:30:05Z 2025-03-19T14:30:05Z 2025-03-19 2025-05 https://pubs.kist.re.kr/handle/201004/151885 Diverse connective tissues exhibit hierarchical anisotropic structures that intricately regulate homeostasis and tissue functions for dynamic immune response modulation. In this study, remotely manipulable hierarchical nanostructures are tailored to exhibit multi-scale ligand anisotropy. Hierarchical nanostructure construction involves coupling liganded nanoscale isotropic/anisotropic Au (comparable to few integrin molecules-scale) to the surface of microscale isotropic/anisotropic magnetic Fe3O4 (comparable to integrin cluster-scale) and then elastically tethering them to a substrate. Systematic independent tailoring of nanoscale or microscale ligand isotropy versus anisotropy in four different hierarchical nanostructures with constant liganded surface area demonstrates similar levels of integrin molecule bridging and macrophage adhesion on the nanoscale ligand isotropy versus anisotropy. Conversely, the levels of integrin cluster bridging across hierarchical nanostructures and macrophage adhesion are significantly promoted by microscale ligand anisotropy compared with microscale ligand isotropy. Furthermore, microscale ligand anisotropy dominantly activates the host macrophage adhesion and pro-regenerative M2 polarization in vivo over the nanoscale ligand anisotropy, which can be cyclically reversed by substrate-proximate versus substrate-distant magnetic manipulation. This unprecedented scalespecific regulation of cells can be diversified by unlimited tuning of the scale, anisotropy, dimension, shape, and magnetism of hierarchical structures to decipher scale-specific dynamic cell-material interactions to advance immunoengineering strategies. English Elsevier Dynamic hierarchical ligand anisotropy for competing macrophage regulation in vivo Article 10.1016/j.bioactmat.2025.01.009 1 Bioactive Materials, v.47, pp.121 - 135 Bioactive Materials 47 121 135 Y scie scopus 001427529800001 2-s2.0-85215116442 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article TISSUE REGENERATION BONE CELL POLARIZATION ADHESION ORDER MODULATION SCAFFOLDS MIGRATION TENDONS Hierarchical ligand nanostructure Multi-scale ligand anisotropy Remote manipulation Reversible macrophage regulation