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Bioact. Mater., Available online 19 January 2025 | https://doi.org/10.1016/j.bioactmat.2025.01.009 Dynamic hierarchical ligand anisotropy for competing macrophage regulation in vivo

Kanghyeon Kim ^a,1, Sunhong Min ^a,1, Ramar Thangam ^a, Kyong-Ryol Tag ^a,b, Hyun-Jeong Lee ^a,b, Jeongyun Heo ^c, Hwapyung Jung ^a, Thet Thet Swe ^a, Iman Zare ^d, Guosheng Song ^e, Alireza Hassani Najafabadi ^f, Junmin Lee ^g, Hyun-Do Jung ^h, Jong Seung Kimⁱ, Sunghoon Hur ^j,k, Hyun-Cheol Song ^j,l,m, Sung-Gyu Park ^n,o, Kunyu Zhang ^p, Pengchao Zhao ^p, Liming Bian ^p, Se Hoon Kim ^c,q, Juyoung Yoon ^r,s, Jae-Pyoung Ahn ^b, Hong-Kyu Kim ^b, Heemin Kang ^a,o,t

^aDepartment of Materials Science and Engineering, Korea University, Seoul, 02841, Republic of Korea
^bAdvanced Analysis Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
^cCenter for Theragnosis, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
^dResearch and Development Department, Sina Medical Biochemistry Technologies Co., Ltd., Shiraz, 7178795844, Iran
^eState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China
^fTerasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064, USA
^gDepartment of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 790-784, Republic of Korea
^hDivision of Materials Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea
ⁱDepartment of Chemistry, Korea University, Seoul, 02841, Republic of Korea
^jElectronic Materials Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea
^kKHU-KIST Department of Converging Science and Technology, Kyung Hee University, Yongin, 17104, Republic of Korea
^lSchool of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
^mKIST-SKKU Carbon-Neutral Research Center, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
ⁿDepartment of Nano-Bio Convergence, Korea Institute of Materials Science (KIMS), Changwon, Gyeongnam, 51508, Republic of Korea
^oDepartment of Future Convergence Materials, Korea University, Seoul, 02841, Republic of Korea
^pSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China
^qKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea
^rDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Republic of Korea
^sGraduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul, 03760, Republic of Korea
^tCollege of Medicine, Korea University, Seoul, 02841, Republic of Korea
¹These authors contribute equally to this work.
Corresponding authors: Hong-Kyu Kim, Heemin Kang

Abstract

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 scale-specific 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.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-22)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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