{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:03:08Z","timestamp":1789534988637,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"APEX-UMFST","award":["CNFIS-FDI-2026-F-070"],"award-info":[{"award-number":["CNFIS-FDI-2026-F-070"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomimetics"],"abstract":"<jats:p>Background\/Objectives: Biomimetic biomaterials should be evaluated not only through their initial properties but also through their interaction with biological environments over time. This study investigated a human cell-based approach integrating flavonoid-induced cellular responses with the temporal evolution of 3D-printed polylactic acid (PLA) scaffolds under physiological-like conditions. Methods: Human Wharton\u2019s Jelly mesenchymal stem cells (WJ-MSCs) were exposed to naringin and hesperidin (250 \u00b5g\/mL) and evaluated after 3, 7, and 10 days using ALP, TP, OPN, and OC. In parallel, PLA scaffolds\u2019 biodegradation was studied under static and dynamic conditions. Results: Naringin produced a more pronounced early\/intermediate osteogenic-related response, whereas hesperidin showed comparatively more sustained ALP- and OPN-related activity at later stages. Dynamic scaffolds exhibited progressive temporal changes, with weight variations ranging from \u22120.384% to +0.127% at days 1, 3, 7, and 10, respectively, accompanied by progressive morphological modification. Initial AFM analysis showed an average RMS roughness of 22.1 nm. Conclusions: The distinct temporal profiles of the flavonoids, together with the evolving scaffold\u2013medium interface, support a biomimetic strategy based on temporal coordination of biochemical cues. These findings provide a rationale for future experimentally validated sequential delivery systems designed to promote early osteogenic activation followed by sustained cellular and matrix-associated activity.<\/jats:p>","DOI":"10.3390\/biomimetics11090654","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:39:24Z","timestamp":1789137564000},"page":"654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward Dynamic Biomimetic Biomaterials: Temporal Coupling of Flavonoid-Induced Cellular Responses and 3D-Printed PLA Scaffold Evolution"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-3434","authenticated-orcid":false,"given":"Diana V.","family":"Portan","sequence":"first","affiliation":[{"name":"Laboratory of Biomechanics and Biomedical Engineering, Department of Mechanical Engineering and Aeronautics, University of Patras, 26504 Patras, Greece"},{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Zoumpoulakis","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry, Analysis & Design of Food Processes, Department of Food Science and Technology, University of West Attica, 12243 Egaleo, Greece"},{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave., 11635 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Kostopoulos","sequence":"additional","affiliation":[{"name":"Applied Mechanics Laboratory, Mechanical Engineering and Aeronautics Department, University of Patras, Rio Campus, 26500 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1937-287X","authenticated-orcid":false,"given":"Ioanna","family":"Pitterou","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry, Analysis & Design of Food Processes, Department of Food Science and Technology, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-9142","authenticated-orcid":false,"given":"Konstantinos","family":"Tsiantas","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry, Analysis & Design of Food Processes, Department of Food Science and Technology, University of West Attica, 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1901-6294","authenticated-orcid":false,"given":"Efstathios","family":"Michalopoulos","sequence":"additional","affiliation":[{"name":"Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-2267","authenticated-orcid":false,"given":"Leonard","family":"Azamfirei","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ziemba, B. 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