{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T21:45:37Z","timestamp":1775943937226,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Cells interact with 3D fibrous platform topography via a nano-scaled focal adhesion complex, and more research is required on how osteoblasts sense and respond to random and aligned fibers through nano-sized focal adhesions and their downstream events. The present study assessed human primary osteoblast cells\u2019 sensing and response to random and aligned medical-grade polycaprolactone (PCL) fibrous 3D scaffolds fabricated via the melt electrowriting (MEW) technique. Cells cultured on a tissue culture plate (TCP) were used as 2D controls. Compared to 2D TCP, 3D MEW fibrous substrates led to immature vinculin focal adhesion formation and significantly reduced nuclear localization of the mechanosensor-yes-associated protein (YAP). Notably, aligned MEW fibers induced elongated cell and nucleus shape and highly activated global DNA methylation of 5-methylcytosine, 5-hydroxymethylcytosine, and N-6 methylated deoxyadenosine compared to the random fibers. Furthermore, although osteogenic markers (osterix-OSX and bone sialoprotein-BSP) were significantly enhanced in PCL-R and PCL-A groups at seven days post-osteogenic differentiation, calcium deposits on all seeded samples did not show a difference after normalizing for DNA content after three weeks of osteogenic induction. Overall, our study linked 3D extracellular fiber alignment to nano-focal adhesion complex, nuclear mechanosensing, DNA epigenetics at an early point (24 h), and longer-term changes in osteoblast osteogenic differentiation.<\/jats:p>","DOI":"10.3390\/nano11112943","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T21:57:49Z","timestamp":1635976669000},"page":"2943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Mechanosensing and Global DNA Methylation of Human Osteoblasts on MEW Fibers"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-1635","authenticated-orcid":false,"given":"Pingping","family":"Han","sequence":"first","affiliation":[{"name":"Center for Oral-Facial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, School of Dentistry, The University of Queensland, Brisbane, QLD 4006, Australia"},{"name":"School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cedryck","family":"Vaquette","sequence":"additional","affiliation":[{"name":"School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-5593","authenticated-orcid":false,"given":"Abdalla","family":"Abdal-hay","sequence":"additional","affiliation":[{"name":"School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia"},{"name":"Department of Mechanical Engineering, Faculty of Engineering, South Valley University, Qena 83523, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5339-0936","authenticated-orcid":false,"given":"Sa\u0161o","family":"Ivanovski","sequence":"additional","affiliation":[{"name":"Center for Oral-Facial Regeneration, Rehabilitation and Reconstruction (COR3), Epigenetics Nanodiagnostic and Therapeutic Group, School of Dentistry, The University of Queensland, Brisbane, QLD 4006, Australia"},{"name":"School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1089\/ten.teb.2017.0287","article-title":"Biomaterial Cues Regulate Epigenetic State and Cell Functions\u2014A Systematic Review","volume":"24","author":"Lv","year":"2018","journal-title":"Tissue Eng. 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