이정환 (단국대학교 조직재생공학연구원/치과대학/나노바이오의과학과) | 한빛사논문 > 한빛사

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단국대학교 조직재생공학연구원/치과대학/나노바이오의과학과

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Adv. Funct. Mater., 19 June 2025 | https://doi.org/10.1002/adfm.202503422 Eco-Fabricated Nanowave-Textured Implants Drive Microtubule-Assisted Nuclear Mechanotransduction and Chromatin Modification: Biophysical Priming for Osteogenesis and Bone Regeneration

Bosu Jeong^1,2, Ji-Young Yoon^3,4,5, Junyong Ahn³^,6, Byunghak Lee², Sung-Min Park^3,4, Jae-Heon Kim^3,6, Buuvee Bayarkhangai^3,4, Yu Jin Kim^3,6, Sak Lee^7,8, Jonathan C. Knowles^4,9,10, Moon-Young Kim¹¹, DongJun Lee^3,12, Sang-Hoon Rhee¹, Hae-Hyoung Lee^3,4,6,9, Hae-Won Kim^{3,4,6,9,13,14,15}, Jung-Hwan Lee^{3,4,5,6,9,13,14}

¹Department of Dental Biomaterials Science, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 03080 Republic of Korea
²Surface Science Research Center, B2LAB Co., Ltd, Seoul, 05836 Republic of Korea
³Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Chungcheongnam-do, 31116 Republic of Korea
⁴Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Chungcheongnam-do, 31116 Republic of Korea
⁵Institute for Stem Cell & Matters, Cell & Matter Corporation, Cheonan, 31116 Republic of Korea
⁶Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Chungcheongnam-do, 31116 Republic of Korea
⁷Department of Oral Pathology, Seoul National University Dental Hospital, Seoul, 03080 Republic of Korea
⁸Department of Oral Pathology, School of Dentistry, Seoul National University, Seoul, 03080 Republic of Korea
⁹UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, Chungcheongnam-do, 31116 Republic of Korea
¹⁰Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF UK
¹¹Department of Oral and Maxillofacial Surgery, College of Dentistry, Dankook University, Cheonan, 31116 Republic of Korea
¹²Department of Oral Histology, Dankook University College of Dentistry, Cheonan, 31116 Republic of Korea
¹³Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116 Republic of Korea
¹⁴Cell & Matter Institute, Dankook University, Cheonan, 31116 Republic of Korea
¹⁵Department of Regenerative Dental Medicine, School of Dentistry, Dankook University, Cheonan, 31116 Republic of Korea

B.J. and J.-Y.Y. contributed equally to this work.
Corresponding Authors: Sang-Hoon Rhee, Hae-Hyoung Lee, Hae-Won Kim, Jung-Hwan Lee

Abstract

The biophysical cues from implantable materials, specifically nanotopography, play a pivotal role in directing cellular lineage specification, thereby accelerating tissue healing and regeneration. Despite the recognized impact of these cues, the mechanisms governing mechano-activated signaling pathways between the cytoskeletal and nuclear domains remain largely unexplored. Here, the processes underlying the enhanced osteogenesis of mesenchymal stem cells (MSCs) driven by nanotextured implants are elucidated, focusing on alterations in cytoskeletal mechanosensitive molecules and nuclear chromatin structures. Using green-processed femtosecond laser fabrication, an implant platform featuring nanowave textures is engineered, inducing cellular alignment with oriented cytoskeletons and consequential changes in nuclear shape. Notably, activated and aligned microtubules alongside the nucleus play a key role in shaping nuclear morphology. The nanowave textures induce significant modifications in chromatin structure, characterized by increased histone acetylation, implying a mechano-priming of MSCs for osteogenesis. Mechanically-primed MSCs exhibit enhanced osteogenic transcriptional responsiveness to biochemical cues, with mechanosensitive YAP co-signaling with the RUNX2, facilitated by an opened chromatin structure. In vivo experiments in a rabbit tibia reveal that nanowave-textured implants promote osteogenesis and bone formation. This study underscores the ability of nanowave-textured cues to transmit mechano-signals across the cytoskeletal-to-nuclear space in MSCs, leading to stimulated osteogenesis.

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