Toward Dynamic Biomimetic Biomaterials: Temporal Coupling of Flavonoid-Induced Cellular Responses and 3D-Printed PLA Scaffold Evolution.

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's Jelly mesenchymal stem cells (WJ-MSCs) were exposed to naringin and hesperidin (250 µg/mL) and evaluated after 3, 7, and 10 days using ALP, TP, OPN, and OC. In parallel, PLA scaffolds' 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 -0.384% 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-medium 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.